connective tissue oncology society 11th annual meeting
DESCRIPTION
Connective Tissue Oncology Society 11th Annual Meeting. NON METASTATIC EWING’ FAMILY TUMORS: HIGH DOSE CHEMOTHERAPY WITH PERIPHERAL BLOOD STEM CELL RESCUE IN POOR RESPONDER PATIENTS: PRELIMINARY RESULTS OF ISG/SSG III PROTOCOL . - PowerPoint PPT PresentationTRANSCRIPT
Connective Tissue Oncology SocietyConnective Tissue Oncology Society11th Annual Meeting11th Annual Meeting
NON METASTATIC EWING’ FAMILY TUMORS: HIGH DOSE NON METASTATIC EWING’ FAMILY TUMORS: HIGH DOSE CHEMOTHERAPY WITH PERIPHERAL BLOOD STEM CELL CHEMOTHERAPY WITH PERIPHERAL BLOOD STEM CELL RESCUE IN POOR RESPONDER PATIENTS: PRELIMINARY RESCUE IN POOR RESPONDER PATIENTS: PRELIMINARY
RESULTS OF ISG/SSG III PROTOCOLRESULTS OF ISG/SSG III PROTOCOL. .
S.Ferrari, A.Tienghi, M.Mercuri, F.Bertoni, E.Barbieri, F.Fossati Bellani, S.Ferrari, A.Tienghi, M.Mercuri, F.Bertoni, E.Barbieri, F.Fossati Bellani, R. Luksch, G. Bernini, A. Brach del Prever, F.Fagioli, R. Luksch, G. Bernini, A. Brach del Prever, F.Fagioli,
P.Picci and G. Bacci P.Picci and G. Bacci Italian Sarcoma Group (ISG);Italian Sarcoma Group (ISG);
S. Smeland, T. Bohling, O. Brosjo, G Saeter, T. Wiebe, T Alvegaard S. Smeland, T. Bohling, O. Brosjo, G Saeter, T. Wiebe, T Alvegaard Scandinavian Sarcoma Group (SSG)Scandinavian Sarcoma Group (SSG)
Diagnosis of Ewing/PNET Sarcoma Diagnosis of Ewing/PNET Sarcoma
No metastases at diagnosisNo metastases at diagnosis
Age between 3-40 yearsAge between 3-40 years
Non-randomized clinical studyNon-randomized clinical study
Induction treatmentInduction treatment
V-Ac-C-A-I-EV-Ac-C-A-I-E
Local treatmentLocal treatment
Surgery whenever possible,Surgery whenever possible,
Radiotherapy, when surgery is not feasible,Radiotherapy, when surgery is not feasible,
or in case of inadequate surgical marginsor in case of inadequate surgical margins
Maintenance treatmentMaintenance treatment
According to the response to induction therapyAccording to the response to induction therapy
ISG/SSG IIIISG/SSG IIIEvaluation of responseEvaluation of response
Good ResponseGood Response
Surgery:Surgery: histologic response G II-III (Picci)histologic response G II-III (Picci)
RxT:RxT: CR to soft tissueCR to soft tissue
Poor responsePoor response
Surgery:Surgery: histologic response G I (Picci)histologic response G I (Picci)
RxT:RxT: persistent disease in soft tissuepersistent disease in soft tissue
VAC VID VAC IE
IE IEVAC VID IE VAC VID VAC VID
IEVACCE BuMel
Local treatment
GR
PR
PBSC harvest
ISG SSG III
VAC
V=vincristine 1.5mg/m2 A=doxorubicin 80mg/m2 C=cyclophosphamide 1200 mg/m2I = ifosfamide 3g/m2/day x 3 D=dactinomycin 1.5mg/m2 E=etoposide 150mg/m2/day x3
C=cyclophosphamide 4000mg/m2 E=etoposide 200mg/m2x3Bu=busulfan 16mg/kg Mel=melphalan 140mg/m2
ISG/SSG III ISG/SSG III Clinical CharacteristicsClinical Characteristics
GENDERGENDER MaleMale
FemaleFemale
152 (63%)152 (63%)
88 (37%)88 (37%)
FEVERFEVER
Available in 225Available in 225
YesYes
NoNo
29 (13%)29 (13%)
196 (87%)196 (87%)
FATIGUEFATIGUE
Available in 216Available in 216
YesYes
NoNo
17 (8%)17 (8%)
199 (92%)199 (92%)
WeightlossWeightloss
Available in 214Available in 214
YesYes
NoNo
11 (5%)11 (5%)
203 (95%)203 (95%)
SAPSAP
Available in 209Available in 209
NormalNormal
HighHigh
185 (89%)185 (89%)
24 (11%)24 (11%)
LDHLDH
Available in 207Available in 207
NormalNormal
HighHigh
145 (70%)145 (70%)
62 (30%)62 (30%)
SiteSite ExtremityExtremity
CentralCentral
PelvisPelvis
130 (54%)130 (54%)
65 (27%)65 (27%)
45 (19%)45 (19%)
Median age (years): 15 (3-40)Median age (years): 15 (3-40)
Median duration of symptoms (months): 4 (0.5-38 )Median duration of symptoms (months): 4 (0.5-38 )
June 1999 - September 2005June 1999 - September 2005 240 patients240 patients
ISG: 203 (85%)ISG: 203 (85%)SSG: 37 (15%)SSG: 37 (15%)
ISG/SSG IIIISG/SSG III
Local treatmentLocal treatment
Surgery 134 (59%)Surgery 134 (59%)Surgery + RxT 49 (21%)Surgery + RxT 49 (21%)RxT 45 (20%)RxT 45 (20%)
228 patients
ISG/SSG IIIISG/SSG III Local treatment by site Local treatment by site
0102030405060708090
Extremity Central Pelvis
SurgerySurgery+RxTRxT
P < 0.0001
ISG/SSG IIIISG/SSG III SURGERY SURGERY
SurgerySurgery Resection Resection 175 (95%) 175 (95%)
Amputation 9 (5%)Amputation 9 (5%)
184 patients184 patients
MarginsMargins
WideWide 128 (80%) 128 (80%)Radical 6 (4%)Radical 6 (4%)MarginalMarginal 18 (11%) 18 (11%)Intralesional 8 (5%)Intralesional 8 (5%)
160 patients160 patients
ISG/SSG IIIISG/SSG III Response Response
ResponseResponse
Good 111 (50%)Good 111 (50%)
Poor 110 (50%)Poor 110 (50%)
221 patients221 patients
NecrosisNecrosis
I 77 (49%)I 77 (49%)
II 38 (24%)II 38 (24%)
III 43 (27%)III 43 (27%)
158 patients158 patients
ISG/SSG IIIISG/SSG III Response by site Response by site
0
10
20
30
40
50
60
70
Extremity Central Pelvis
GRPR
P=0.043
ISG/SSG IIIISG/SSG III Histologic response by site Histologic response by site
0
10
20
30
40
50
60
70
Extremity Central Pelvis
PR gIGR g II-III
P=0.4
ISG/SSG IIIISG/SSG III
ISG/SSGISG/SSG % (95% CI)% (95% CI)
3-year PFS3-year PFS 67 (60-75)67 (60-75)
3-year OS3-year OS 78 (72-85)78 (72-85)
Median FU 29 months (1-75)Median FU 29 months (1-75)
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Progression-free survival Overall survival
ISG/SSG III Progression-free survivalISG/SSG III Progression-free survivalSITESITE
Extremity 3 yrs PFS 70% (61-80)Extremity 3 yrs PFS 70% (61-80)Central 3 yrs PFS 62% (46-77)Central 3 yrs PFS 62% (46-77)Pelvis 3 yrs PFS 60% (43-76)Pelvis 3 yrs PFS 60% (43-76)P=0.3P=0.3
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0 10 20 30 40 50 60 70 80Time
Event Times (PELVI/SACRO)
Cum. Survival (PELVI/SACRO)
Event Times (ESTR)
Cum. Survival (ESTR)
Event Times (CENTR)
Cum. Survival (CENTR)
ISG/SSG III Progression-free survivalISG/SSG III Progression-free survivalLocal treatmentLocal treatment
Surgery 3 yrs PFS 72% (63-81)Surgery 3 yrs PFS 72% (63-81)Surgery+RxT 3 yrs PFS 68% (52-83)Surgery+RxT 3 yrs PFS 68% (52-83)RxT 3 yrs PFS 51% (33-68)RxT 3 yrs PFS 51% (33-68)RxT No PD 3 yrs PFS 57% (39-76)RxT No PD 3 yrs PFS 57% (39-76)P =0.09P =0.09
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Event Times (RxT)
Cum. Survival (RxT)
Event Times (RxT + Surgery)
Cum. Survival (RxT + Surgery)
Event Times (Surgery)
Cum. Survival (Surgery)
ISG/SSG III Progression-free survivalISG/SSG III Progression-free survivalRESPONSERESPONSE
GR 3 yrs PFS 70% (61-80)GR 3 yrs PFS 70% (61-80)PR 3 yrs PFS 62% (51-73)PR 3 yrs PFS 62% (51-73)P=0.19P=0.19
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0 10 20 30 40 50 60 70 80Time
Event Times (PR)
Cum. Survival (PR)
Event Times (GR)
Cum. Survival (GR)
ISG/SSG IIIISG/SSG III
No High Dose ChemotherapyNo High Dose Chemotherapy
22/110 poor responder patients did not get HDC 22/110 poor responder patients did not get HDC
PDPD 66
Poor harvestPoor harvest 22
Medical contraindicationMedical contraindication 44
Refusal/medical decisionRefusal/medical decision 1010
ISG/SSG III Progression-free survivalISG/SSG III Progression-free survivalRESPONSERESPONSE
0
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Event Times (PR)
Cum. Survival (PR)
Event Times (GR)
Cum. Survival (GR)
GR 3 yrs PFS 70% (61-80)GR 3 yrs PFS 70% (61-80)PR 3 yrs PFS 68% (57-80)PR 3 yrs PFS 68% (57-80)P=0.7P=0.7
ISG/SSG III Progression-free survivalISG/SSG III Progression-free survivalHISTOLOGIC RESPONSEHISTOLOGIC RESPONSE
I 3 yrs PFS 66% (54-79)I 3 yrs PFS 66% (54-79)II 3 yrs PFS 70% (55-86)II 3 yrs PFS 70% (55-86)III 3 yrs PFS 83% (70-95)III 3 yrs PFS 83% (70-95)P=0.18P=0.18
0
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Event Times (III)
Cum. Survival (III)
Event Times (II)
Cum. Survival (II)
Event Times (I)
Cum. Survival (I)
ISG/SSG III ISG/SSG III EventsEvents
PDPD LRLR LR+LR+
otherotherBoneBone LungLung Bone+Bone+
LungLung
6 (11%)6 (11%) 10 (18%)10 (18%) 8 (14%)8 (14%) 8 (14%)8 (14%) 18 (32%)18 (32%) 6 (11%)6 (11%)
G4 cardiotox, Pneumonia, Septic emboli 10 months after chemo completionAML 2 patients
The treatment is feasible The treatment is feasible and well toleratedand well tolerated
Results are encouragingResults are encouraging
The strategy for poor responders The strategy for poor responders seems to improve their prognosisseems to improve their prognosis
Longer follow-up is needed to confirm its Longer follow-up is needed to confirm its efficacyefficacy
ISG SSG III