sarcoma jaume mora de ewing - grupo geis · fractura con dificultad de consolidación. • rmn...
TRANSCRIPT
SARCOMA DE EWING
Enfermedad localizada
Enfermedad metastaacutesica
Jaume Mora
Oncologiacutea Pediaacutetrica
Hospital Sant Joan de Deu
Claudia Mordf ValverdeOncologiacutea Meacutedica
Hospital Universitario Vall dacuteHebroacuten
Barcelona
CARACTERIacuteSTICAS
SARCOMA
EWING OSTEOSARCOMA CONDROSARCOMA CORDOMA TCG
100000habantildeo 01 04 02 ltlt 012
Pico incidencia AYA bimodal 40s-60s 60s 20-40s
Primario
EEIIgtEESSgt
pared toacuterax metaacutefisis hlargos
pelvis y feacutemur
proximal
sacro-base
craacuteneo
epifisis
huesos largos
Tendencia M1 +++ +++(alto grado) + (desdiferenciado) + (1) + (1)
QTsensibilidad +++ ++ + + +
RTsensibilidad +++ + + +b +
bull Mujer 46 antildeos
bull A partir de entorsis de repeticion en tobillo en mar16 y evolucion toacuterpida de una fractura de piloacuten y posterioresfractura por insuficiencia se objetiva hallazgo de lesion de partes blandas con sospecha de afectacionoacutesea enmusculatura flexora del pie
European Intergroup Cooperative Ewing Sarcoma
studies (N=1426)
bull RMN (211216) Fractura no desplazada en tibia distal con imagen sugestiva de infarto oacuteseo Leve tendinitis del m tibial posterior y flexor de los dedos Distensioacutendesgarro del fibrilar subagudo del ligamento peroneo-astragalino anterior
bull g-oacutesea (23117) lesioacuten oacutesea distal tibia dcha compatible en 1ordm lugar con fractura con dificultad de consolidacioacuten
bull RMN (21317) Alteracioacuten de la sentildeal en diafisis distal metaacutefisis y epiacutefisis tibia dcha Lesioacuten de partes blandas de 56x24 cm posterior con infiltracioacuten de m flexor de 1ordm dedo y tendoacuten de tibialposterior
ESTUDIO RADIOLOacuteGICO
- Hueso
- PatroacutenHISTORIA Y EXPLORACION
Edad
Sexo
Dolor edemahellip
ANATOMIacuteA PATOLOacuteGICA
-Patroacuten calcificaciones condroide
- IHQ molecular
Diagnoacutestico (en la era molecular)
7
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
CARACTERIacuteSTICAS
SARCOMA
EWING OSTEOSARCOMA CONDROSARCOMA CORDOMA TCG
100000habantildeo 01 04 02 ltlt 012
Pico incidencia AYA bimodal 40s-60s 60s 20-40s
Primario
EEIIgtEESSgt
pared toacuterax metaacutefisis hlargos
pelvis y feacutemur
proximal
sacro-base
craacuteneo
epifisis
huesos largos
Tendencia M1 +++ +++(alto grado) + (desdiferenciado) + (1) + (1)
QTsensibilidad +++ ++ + + +
RTsensibilidad +++ + + +b +
bull Mujer 46 antildeos
bull A partir de entorsis de repeticion en tobillo en mar16 y evolucion toacuterpida de una fractura de piloacuten y posterioresfractura por insuficiencia se objetiva hallazgo de lesion de partes blandas con sospecha de afectacionoacutesea enmusculatura flexora del pie
European Intergroup Cooperative Ewing Sarcoma
studies (N=1426)
bull RMN (211216) Fractura no desplazada en tibia distal con imagen sugestiva de infarto oacuteseo Leve tendinitis del m tibial posterior y flexor de los dedos Distensioacutendesgarro del fibrilar subagudo del ligamento peroneo-astragalino anterior
bull g-oacutesea (23117) lesioacuten oacutesea distal tibia dcha compatible en 1ordm lugar con fractura con dificultad de consolidacioacuten
bull RMN (21317) Alteracioacuten de la sentildeal en diafisis distal metaacutefisis y epiacutefisis tibia dcha Lesioacuten de partes blandas de 56x24 cm posterior con infiltracioacuten de m flexor de 1ordm dedo y tendoacuten de tibialposterior
ESTUDIO RADIOLOacuteGICO
- Hueso
- PatroacutenHISTORIA Y EXPLORACION
Edad
Sexo
Dolor edemahellip
ANATOMIacuteA PATOLOacuteGICA
-Patroacuten calcificaciones condroide
- IHQ molecular
Diagnoacutestico (en la era molecular)
7
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull Mujer 46 antildeos
bull A partir de entorsis de repeticion en tobillo en mar16 y evolucion toacuterpida de una fractura de piloacuten y posterioresfractura por insuficiencia se objetiva hallazgo de lesion de partes blandas con sospecha de afectacionoacutesea enmusculatura flexora del pie
European Intergroup Cooperative Ewing Sarcoma
studies (N=1426)
bull RMN (211216) Fractura no desplazada en tibia distal con imagen sugestiva de infarto oacuteseo Leve tendinitis del m tibial posterior y flexor de los dedos Distensioacutendesgarro del fibrilar subagudo del ligamento peroneo-astragalino anterior
bull g-oacutesea (23117) lesioacuten oacutesea distal tibia dcha compatible en 1ordm lugar con fractura con dificultad de consolidacioacuten
bull RMN (21317) Alteracioacuten de la sentildeal en diafisis distal metaacutefisis y epiacutefisis tibia dcha Lesioacuten de partes blandas de 56x24 cm posterior con infiltracioacuten de m flexor de 1ordm dedo y tendoacuten de tibialposterior
ESTUDIO RADIOLOacuteGICO
- Hueso
- PatroacutenHISTORIA Y EXPLORACION
Edad
Sexo
Dolor edemahellip
ANATOMIacuteA PATOLOacuteGICA
-Patroacuten calcificaciones condroide
- IHQ molecular
Diagnoacutestico (en la era molecular)
7
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
European Intergroup Cooperative Ewing Sarcoma
studies (N=1426)
bull RMN (211216) Fractura no desplazada en tibia distal con imagen sugestiva de infarto oacuteseo Leve tendinitis del m tibial posterior y flexor de los dedos Distensioacutendesgarro del fibrilar subagudo del ligamento peroneo-astragalino anterior
bull g-oacutesea (23117) lesioacuten oacutesea distal tibia dcha compatible en 1ordm lugar con fractura con dificultad de consolidacioacuten
bull RMN (21317) Alteracioacuten de la sentildeal en diafisis distal metaacutefisis y epiacutefisis tibia dcha Lesioacuten de partes blandas de 56x24 cm posterior con infiltracioacuten de m flexor de 1ordm dedo y tendoacuten de tibialposterior
ESTUDIO RADIOLOacuteGICO
- Hueso
- PatroacutenHISTORIA Y EXPLORACION
Edad
Sexo
Dolor edemahellip
ANATOMIacuteA PATOLOacuteGICA
-Patroacuten calcificaciones condroide
- IHQ molecular
Diagnoacutestico (en la era molecular)
7
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull RMN (211216) Fractura no desplazada en tibia distal con imagen sugestiva de infarto oacuteseo Leve tendinitis del m tibial posterior y flexor de los dedos Distensioacutendesgarro del fibrilar subagudo del ligamento peroneo-astragalino anterior
bull g-oacutesea (23117) lesioacuten oacutesea distal tibia dcha compatible en 1ordm lugar con fractura con dificultad de consolidacioacuten
bull RMN (21317) Alteracioacuten de la sentildeal en diafisis distal metaacutefisis y epiacutefisis tibia dcha Lesioacuten de partes blandas de 56x24 cm posterior con infiltracioacuten de m flexor de 1ordm dedo y tendoacuten de tibialposterior
ESTUDIO RADIOLOacuteGICO
- Hueso
- PatroacutenHISTORIA Y EXPLORACION
Edad
Sexo
Dolor edemahellip
ANATOMIacuteA PATOLOacuteGICA
-Patroacuten calcificaciones condroide
- IHQ molecular
Diagnoacutestico (en la era molecular)
7
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
ESTUDIO RADIOLOacuteGICO
- Hueso
- PatroacutenHISTORIA Y EXPLORACION
Edad
Sexo
Dolor edemahellip
ANATOMIacuteA PATOLOacuteGICA
-Patroacuten calcificaciones condroide
- IHQ molecular
Diagnoacutestico (en la era molecular)
7
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
7
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
8
DIAGNOacuteSTICO Y EXTENSIOacuteN
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Estoy en un CENTRO DE REFERENCIAALTO VOLUMEN
bull En caso afirmativo Diagnoacutestico y Tratamiento
bull
bull En caso negativo REMITIR
iexcl No hacer biopsia
Los estudios muestran un impacto en la supervivencia global
(Stiller 2000 y 2006)
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
PILARES DEL TRATAMIENTO
TRATAMIENTO LOCAL
bull CIRUGIA yo RADIOTERAPIA
TRATAMIENTO SISTEacuteMICO
bull QUIMIOTERAPIA
Mayo Clin Proc 2012 May 87(5) 475ndash487
Common Musculoskeletal Tumors of Childhood and Adolescence
Carola AS Arndt Peter S Rose Andrew L Folpe Nadia N Laack
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
PRINCIPIOS BAacuteSICOS DE LA CIRUGIacuteA
El tratamiento de los sarcomas ha de ajustarse a las leyes de la cirugiacutea ortopeacutedica oncoloacutegica cuyos objetivos ordenados en importancia son los siguientes
bull Salvar la vida de los pacientes
bull Conseguir la mejor funcionalidad del miembro con cirugiacutea conservadora o con la amputacioacuten
NO SE DEBE INTERVENIR NINGUacuteN PACIENTE QUE NO SEA
PRESENTADO EN EL COMITEacute MULDISCIPLINARIO
Se debe re-estadificar tras las terapias neoaduvantes y con estas pruebas se planifica el tipo de cirugiacutea
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull RESECCIOacuteN ONCOLOacuteGICA
bull Conservadora vs amputacioacuten
bull RECONSTRUCCIOacuteN ORTOPEacuteDICA
bull oacutesea y de tejidos blandos
PLANIFICACIOacuteN QUIRUacuteRGICA
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull La cirugiacutea suele ser el enfoque preferido siempre que la lesioacuten sea resecable
bull Esta aparente superioridad puede representar un sesgo en la seleccioacuten
ndash Los tumores maacutes pequentildeos y perifeacutericos tienen mayor posibilidad de tratarse con cirugiacutea
ndash Los tumores maacutes grandes y maacutes centrales tienen mayor posibilidad de tratarse con radioterapia
bull NO se comprobado la superioridad de la reseccioacuten para el control local durante un estudio prospectivo aleatorizado
bull En nintildeos la cirugiacutea tiene menos morbilidad que la radioterapia ya que esta puede causar retardo del crecimiento
bull Otro beneficio de la cirugiacutea es la informacioacuten que se puede recabar al analizar la pieza tumoral (necrosis)
Oberlin O Deley MC Bui BN et al Prognostic factors localized Ewings tumours amp peripheral neuroectodermal tumours Br J Cancer 85 (11) 1646-54 2001
Yock TI Krailo M Fryer CJ et al Local control in pelvic Ewing sarcoma analysis from INT-0091 a report from the Childrens Oncology Group Clin Oncol 24 (24)
3838-43 2006
iquestCONTROL LOCAL CON CIRUGIacuteA O RADIOTERAPIA
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
SARCOMA DE EWING
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
CD99
17 yo
Male
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
2013
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
iquestImprescindible el estudio molecular en todos los casos
1 Subtipos morfoloacutegicos infrecuentes
2 Presentaciones cliacutenico-radioloacutegicas poco comunes
ESMO guidelines 2012
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
SECUENCIA DE TRATAMIENTO
QT
neoadyuvante
Tratamiento
local
IQ yo RTQT
adyuvante
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Un poco de historia
1962 ndash Sutow amp Pinkel ndash Cyclophosphamide- frac34 response
1966 ndash Jenkin ndash N2 mustard ndash 33 response
1968 ndash Hustu ndash comb ndash V+C amp RT- sustained resp-5 pt
1976 ndash Jaffee- sup survival ndash VAC vs Single agent
1976 ndash Rosen MSKCC- RT+ VACD comb- long term survival 12 pts
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Paulussen et al The Oncologist 200611503ndash519
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
M0
The 5 year EFS
exper group - 69
Standard - 54
M1
The 5 year EFS
exper - 22 plusmn 5
Standard - 22 plusmn 6
Grier H et al N Engl J Med 2003348694-701
Improvement greatest with large primary tumors or
primary tumors of the pelvis
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Paulussen et al The Oncologist 200611503ndash519
No benefit of dose-intense
Womer
et alCOG VACIE 21d
VACIE 14d
4865
73
Benefit of dose-dense (lt17)
Similar toxicity
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
EuroEwing 2012GEIS 341ordf liacutenea (faseII III)
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull 1ordf liacutenea de tratamiento dentro de estudio EuroEwing 2012 se randomiza ( R1) al brazo A de tratamiento VIDE x 6 ciclos C1D1 13617 con cuasi CR local desaparicioacuten de noacutedulos pumonaresinespeciacuteficos milimeacutetricos tras 6 ciclos C5 y C6 VIDE sin VP16 x nuevo episodio de neutropenia febril + GCSF
bull IQ 301117 exeacuteresis tumor piloacuten tibial der y reconstruccioacuten con aloinjerto AP 5x4 cm maacutergenes libres pero 15 ceacutelulas viables-gt poor response
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull Como paciente de pobre pronoacutestico ( celularidad tumoral viable gt10) ha recibido consolidacioacuten con 1 ciclo VAI y MelBu altas dosis ( Melfalaacuten140mgm2 diacutea -2 Busulfan 32 mgKg diacutea -6 a -3 30118-3218) con autotransplante 5218 Randomizada a rama ac zoledroacutenico del que ha recibido 5 ciclos ( 1ordf dosis conjuntamente con VAI)
bull Comentado en comiteacute se decide no RT adyuvante
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
31
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
33
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
rECurrGEIS 35 2ordf liacutenea
bull Estudio Fase IIIII para pacientes con enfermedad en progresioacuten tras 1ordf liacutenea
bull Tratamiento randomizado a
bull 1 IV ciclofosfamida 250 mgm D1-5 amp IV topotecan 075 mgm D1-5
bull 2 IV irinotecan 50 mgm D1-5 amp temozolomida 100 mgm D1-5
bull 3 IV ifosfamida 3000 mgm D1-5
bull 4 IV gemcitabina 1000 mgm D18 amp IV docetaxel 100 mgm D8-gt STOP
bull Objetivo tasa de respuestas y supervivencia libre de progresioacuten
bull Los pacientes han de poder randomizarse a al menos 2 brazos de tratamiento
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
Internal use
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull JUNE 2013
Internal use
Ewing Family of Sarcomas
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull Malignant cell
population
bull infiltrating growth
bull small blue round cell
bull some mitoses
bull PAS positive (glycogen)
bull CD99Mic2 positive
bull -+ neuronal differentiation
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
CD99
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
J Neurosurg (5 Suppl Pediatrics) 107411ndash415 2007
Primary Ewing sarcoma of the tentorium presenting with intracranial
hemorrhage in a child
Case report and review of the literature
RAMON NAVARRO ASTRID LAGUNA CARMEN DE TORRES JUAN CRUZ
CIGUDOSA MARIONA SUNtildeOL OFELIA CRUZ AND JAUME MORA
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
1 2 3 4 5 6 7 8 9 10 11 12 (helliphasta 17)
EWS 22q12
1 2 3 4 5 6 7 8 9
FLI1 11q24
1 2 3 4 5 6 7 6 7 8 9EWS-
FLI1
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
EWSR1 Break-a-part FISH Test
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull SEPTEMBER 2014
Ewing Family of Sarcomas
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
10072013 Tumor parafinado FISH EWSR1 +
PCR conv qPCR
11072013 Ant dcha MO-4422 Neg
Ant izda MO-4423 Neg
Post dcha MO-4424 Neg 1 pocillo ciclo 39
Post izda MO-4425 Neg
17092013 Ant dcha MO-4538 Neg
Ant izda MO-4539 Neg
Post dcha MO-4540 Neg
Post izda MO-4541 Neg
28112013 Ant dcha MO-4669 Neg
Ant izda MO-4670 Neg
Post dcha MO-4671 Neg
Post izda MO-4672 Neg
13022014 Ant dcha MO-4836 Neg
Ant izda MO-4837 Neg 1 pocillo ciclo 41
Post dcha MO-4838 Neg
Post izda MO-4839 Neg
01072014 Ant dcha MO-5061 Neg
Ant izda MO-5062 Neg
Post dcha MO-5063 Neg
Post izda MO-5064 Neg
29092014 Recaiacuteda congeladoEWS-FLI1
tipo2
Ant dcha MO-5276 Neg
Ant izda MO-5277 Neg
Post dcha MO-5278 Neg
Post izda MO-5279 Neg
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Osteomielitis
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
1
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
fli1-ews
1
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Figure 119 The Biology of Cancer (copy Garland Science 2007)
EWS
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull Non EWSR1 ndash ETS Fusions
Ewing Family of Sarcomas
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
EWS-FLI1
EWS-FLI1
1 EWS-FLI1 TARGETS amp DISRUPTS
BIVALENT DOMAINS (loss of H3K27me3)
2 RING1B COOPERATES WITH EWS-FLI1
IN PROMOTER REGULATION
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Figure 1 Initial presentation
of patient 1 A MRI image
of the cervical region
showing the intramuscular
hemangioma
B Microscopic view of the
hemangioma showing the
characteristic diffuse sheet of
tumor cells with no mitosis or
atypical cells (original
magnification 400x) C
Immunohistochemistry of the
hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) D
Fluorescence insitu-
hybridization using Vysis LSI
EWSR1 (22q12) Dual Color
Break Apart Rearrangement
Probe Arrow show the
separation of the signals in
single cell nuclei indicating
the rearrangement of
EWSR1
Vascular Tumors Preceding Ewing
Sarcoma ClinicoPathological
Observations Sarcoma Res Int - Volume 2 Issue 3 - 2015
At 11 months of age
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Figure 2 Three and half
yearrsquos later local
recurrence of patient 1
A Microscopic view of the
recurrent hemangioma
showing the characteristic
diffuse sheet of tumor cells
(original magnification 400x)
B Immunohistochemistry of
the hemangioma showing
positive membrane staining
for the glucose transport
protein GLUT-1 (Original
magnification 400x) C
Fluorescence in-situ-
hybridization using the Vysis
LSI EWSR1 (22q12) Dual
Color Break Apart
Rearrangement Probe Arrow
shows the separation of the
signals in single-cell nuclei
indicating the rearrangement
of EWSR135 years later
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Figure 3 Disseminated presentation of ES of patient 1 A MRI coronal image
of lumbar region showing the right paravertebral tumor B Microscopic view of
the tumor showing the characteristic features of Ewing tumor cells invading the
muscle (original magnification 400x)
At 5 years of age
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
CESS 81 - EICESS 92
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Diagnoacutestico Fin 3er ciclo Fin Tratamiento
RM 06042010 RM 2062010 TC 25112010
Localized disease Appendicularskeleton
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
RM 09022012
Diagnoacutestico Fin de ventana
RM 03042012
Fin de 3er ciclo
RM 24052012
Localized disease Axial Skeleton Pelvis
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
RM 12072010RM 17052010
Diagnoacutestico Fin de fase ventana Fin de 3er ciclo
RM 07092010
Localized disease Axial Skeleton Pelvis
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for
the treatment of Ewing sarcoma of children and adults a report from the Spanish sarcoma group (GEIS)
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
GEIS-21 a multicentric phase II study of intensive chemotherapy including gemcitabine
and docetaxel for the treatment of Ewing sarcoma of children and adults a report from
the Spanish sarcoma group (GEIS)
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
April 2008
Fluorine-18 fluorodeoxyglucose PET
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Monthly GD therapy
April 2008 Nov 2008
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
July 2010
B10-3008 SJDES07
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
03 06 2011
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
B07-4447 B10-3008
SJDES07
B11-3090
SJDES23
STAG2
p53
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull Dra Cleofeacute Romagosa
CURSO PRESENCIAL
MASTER EN SARCOMAS
Histopatologiacutea del Sarcoma
de Ewing
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
bull Edad
bull Localizacioacuten
bull Reaccioacuten perioacutestica
bull PAS+
bull FISHNGS
EWSR1-ETS family
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
BCO
R
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
Large cell variant EWS
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
- Metafisario
- Hombre 23 antildeos
Osteosarcoma
de ceacutelula
redonda
ETV
4
WT1
TLE1 BCOR
ETV
4
WT1
TLE1 BCOR
TLE1 BCOR