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Sarcoma Medical therapy Paolo G. Casali [email_address]
Incidence STS   5  /100,000/year GIST   1.5 Osteosa   0.3  Ewing   0.2 Rhabdomyosa   0.1 benign tumors 300 Sex M  >  F Med...
STS OS EFT RMS
STS OS EFT RMS
Soft tissue sarcoma
Adipocytic tumours Well deifferentiated / dedifferentiated liposarcoma Myxoid / round cell liposarcoma Pleomorphic liposar...
…… .
Head & neck     5% Superficial trunk 10% Retroperitoneum   15% Viscera   10% Limbs 60%
Adjuvant chemotherapy L  = limbs –  T  = trunk –  HN  = head & neck –  R  = retrop –  U  = uterus –  V  = viscera gruppo a...
 
Localized disease Woll PJ, ASCO Ann meet 2007; #10008
Frustaci S et al, J Clin Oncol 2001;19:1238
 
0  epiADM+IFX x 3
 
 
 
LOCALIZED, HIGH-RISK SOFT TISSUE SARCOMAS (STS) OF THE EXTREMITIES AND TRUNK WALL IN ADULTS: THREE VS FIVE CYCLES OF FULL-...
 
Epirubicin 120 mg/m 2  ( ~  DOX 80 mg/m 2 ) + Ifosfamide 9,000 mg/m 2   q 21 days
OS by study arm 70% 69% one-sided 95%: 0.941 (95% CI 0.664 - 1.334)  70% 69% N. at risk Arm A 164 154 138 106 77 43 Arm B ...
RFS by study arm 61% 60% N. at risk Arm A 156 123 108 74 55 33 Arm B 158 126 108 77 47 31
OS vs previous ISG trial
Sarcomas: spread of disease local isolated extra pulmonary pulmonary
Isolated pulmonary  metastatic disease
 
Advanced disease R ADM 75 mg/sqm + IFX 7.5 g/sqm ADM 75 mg/sqm EORTC Soft Tissue & Bone Sarcoma Group
ADM vs ADM+IFX in advanced STS <ul><li>no. pts. Regimen OR OS </li></ul><ul><li>ECOG , 1993  90 ADM 80 mg/mq 20% = </li></...
ADM vs ADM+IFX in advanced STS no. pts. Regimen  OR OS EORTC , 1991  244 ADM 75 mg/mq 24% = 233 ADM 50 mg/mq 27% = IFX 500...
OR OS Duration of response 218 d (PR) 243 d (CR) Time to progression 240 d (SD) 288 d (PR) 317 d (CR)
…… .
 
Endometrial stromal sarcoma: progestins, aromatase inhibitors ER PR
Dermatofibrosarcoma: Imatinib COL1A1-PDGFB     PDGFB t(17;22)
Desmoid tumors (aggressive fibromatosis)
 
 
L LMS
 
Stacchiotti S et al, Ann Oncol 2010, 21:1130
 
 
Stacchiotti S et al, Mol Cancer Ther 2010;9:1286
 
PEComas <ul><li>Kidney    </li></ul><ul><li>Liver </li></ul><ul><li>Gastrointestinal tract </li></ul><ul><li>Prostate </li...
 
Laplante et Sabatini, J Cell Science 2009
SUCCEED study standard CT: best response R Ridaforolimus placebo in advanced STS
Leiomyosarcoma: Dacarbazine 0  DTIC x 2
Dedifferentiated liposa: HD-IFX 0  HD-ci-IFX x 5
Sinovyal sa: HD-IFX 0  +3 mos
Angiosarcoma: taxanes Fata F et al. Cancer 1999; 86: 2034
 
Angiosarcoma: Gemcitabine 0  +1 mos  +4 mos
Leiomyosarcoma: Gemcitabine
 
 
A pooled analysis of the final results of the two randomized phase II studies comparing Gemcitabine (G)  vs  Gemcitabine +...
Pooled analysis – Progression-free survival
Pooled analysis – Progression-free survival
Trabectedin (ET-743)
L -sarcoma liposarcoma leiomyosarcoma
Dedifferentiated liposa 0  ET743 x 16 mos
Uterine leiomyosarcoma 0  ET743 x 3
Lipo sarcoma well diff    dediff myxoid    round cell pleomorphic
well diff    dediff myxoid    round cell pleomorphic
t(12;16)(q13;p11) FUS CHOP 12 16 FUS/CHOP q13 p11
 
 
0   + 1 c  +4 c
 
Mol Cancer Therap 2009;8:449
Synovial sa: Trabectedin
T -STS simple cariotype with reciprocal translocations complex cariotype
Synovial sa t(X;18)(p11;q11) SS18-SSX1 SS18-SSX2 SS18-SSX4 Myxoid liposa t(12;16)(q13;p11) FUS-CHOP t(12;22)(q13;q12) EWS-...
<ul><li>Leiomiyosarcoma : GEM, Trabectedin, DTIC (& Temozolomide), ….. </li></ul><ul><li>Liposarcoma, dediff : Trabectedin...
<ul><li>Dermatofibrosarcoma : Imatinib </li></ul><ul><li>Desmoids : hormones, Imatinib, Sorafenib, ….. </li></ul><ul><li>A...
Gastrointstinal stromal tumors (GIST)
Target therapy in GIST Imatinib SCF
 
 
Imatinib chemotherapy OS months
 
KIT (CD 117)
Lasota J et al, Histopathology 2008 exon  9  (~10%)  exon  11  (~70%)  exon  13  (~5%)  exon  17  (~5 %)  PDGFRA  (~10%)  ...
KIT exon 9
KIT exon 9 PDGFRA
 
PDGFRA Corless CL, J Clin Oncol 2005, 23: 5357
GIST in syndromes GIST in children 0 – 18+ yrs
 
 
 
Tumor response
 
Tumor response:  Choi’s criteria 10% 15%
5 HU 57 HU 39 HU 13 HU 61 HU 15 HU 83 HU 36 HU 57 HU 9 HU 52 HU 3 HU - 2 HU - 18 HU -34 HU 9 HU 5 HU -9 HU -13 HU 3 HU 20 ...
PET scan
0  +3-4 wks  +12 mos  +18 mos
50 mg/day, 4 weeks on, 2 weeks off SUNITINIB
Van den Abbeele  AD et al, ECCO Ann meet 2005
Sunitinib:  interval progression
Imatinib: interval progression
t
BFR14 study R stop Imatinib continue Imatinib Imatinib CR PR SD <ul><li>12 mos </li></ul><ul><li>surgery if feasible </li>...
from: ASCO 2009 Virtual Meeting Duffaud F et al, ASCO Ann meet 2009; #10508
Duffaud F et al, ASCO Ann meet 2009; #10508 from: ASCO 2009 Virtual Meeting
Time to secondary resistance…
 
Secondary resistance
Sunitinib VEGFR-2 VEGFR-1 VEGFR-3 PDGFR-  KIT FLT-3 PDGFR-  RET N H O N H F H 3 C CH 3 N H O N CH 3 CH 3
 
Negri T al,  J Natl Cancer Inst 2009;101:194
Secondary resistance: molecular heterogeneity Liegl B, J Pathol, 2008;216:64
KIT PDGRA VEGFR …… ..
KIT PDGRA VEGFR …… ..
KIT PDGRA VEGFR PI3K AKT mTOR …… ..
KIT PDGRA VEGFR Hsp90 …… ..
GIST: rechallenge with Imatinib  0 +1 mos
Surgery of  responding  residual disease 
n = 27 n = 8 Gronchi A, Ann Surg 2007; 245:341
Raut CP, J Clin Oncol 2006;24:2325
 
DeMatteo R et al, Lancet 2009
OS RFS
R OS relapse RFS OS Imatinib Imatinib
R R relapse R relapse Imatinib Imatinib Imatinib
R R relapse R relapse Imatinib Imatinib Imatinib
R R relapse R relapse Imatinib Imatinib Imatinib
R R relapse R relapse Imatinib Imatinib Imatinib
Paolo G. Casali Study Chair & ISG Coordinator Jean-Yves Blay EORTC Coordinator Axel Le Cesne FSG Coordinator Andres Poveda...
R Imatinib x 2 yrs control
German/Scandinavian trial R Imatinib x 3 yrs Imatinib x 1 yr
Risk stratification Miettinen M. Semin Diagn Pathol 2006; 23: 70 cm M/50HPF gastric jejunal/ ileal duodenal rectal 1 < 2 <...
Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
Osteosarcoma
Osteosarcoma
 
N Engl J Med 1986;314:1600
Cancer 1979; 43: 2163-2177
Cancer 1979; 43: 2163-2177
Goorin AM et al. J Clin Oncol 2003; 21: 1574
Goorin AM et al. J Clin Oncol 2003; 21: 1574
J Clin Oncol 1994;12:2699
 
J Clin Oncol 1988;6:329
J Natl Cancer Inst 2007;99:112
 
 
+ IFX +  IFX + MTP + MTP +  IFX + MTP P<0.05 + IFX + MTP
Ewing’s sarcoma
Ewing’s sarcoma
 
Cancer  1974;33:384
J Clin Oncol 1990;8:1664
N Engl J Med 2003;348:694
 
J Clin Oncol 1993;11:1763
Ann Oncol  2010; Nov 8 Epub
Lancet Oncol 2010;11:129
 
 
[email_address]
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MCO 2011 - Slide 31 - P. Casali - Spotlight session Sarcoma

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MCO 2011 - Slide 31 - P. Casali - Spotlight session Sarcoma

  1. 1. Sarcoma Medical therapy Paolo G. Casali [email_address]
  2. 2. Incidence STS 5 /100,000/year GIST 1.5 Osteosa 0.3 Ewing 0.2 Rhabdomyosa 0.1 benign tumors 300 Sex M > F Median age STS 60 y GIST 60 y Osteosa 15 y Ewing 15 y Rhabdomyosa 5 y
  3. 3. STS OS EFT RMS
  4. 4. STS OS EFT RMS
  5. 5. Soft tissue sarcoma
  6. 6. Adipocytic tumours Well deifferentiated / dedifferentiated liposarcoma Myxoid / round cell liposarcoma Pleomorphic liposarcoma … .. Fibroblastic / myofibroblastic tumours Fibromatosis (desmoid) Solitary fibrous tumour / haemangiopericytoma Low grade myofibroblastic tumour Infantile fibrosarcoma Adult fibrosarcoma Mixofibrosarcoma … .. So-called fibrohistiocytic tumours Pleomorphic MFH / Undifferentiated pleomorphic sarcoma … .. Smooth muscle tumours Leiomyosarcoma … .. Skeletal muscle tumours Embryonal rhabdomyosarcoma Alveolar rhabdomyosarcoma Pleomorphic rhabdomyosarcoma Vascular tumours Epithelioid haemangioendothelioma Angiosarcoma of soft tissue … .. Chondro-osseous tumours Mesenchymal chondrosarcoma Extraskeletal osteosarcoma Tumours of uncertain differentiation Synovial sarcoma Epithelioid sarcoma Alveolar soft part sarcoma Clear cell sarcoma of soft tissue Extraskeletal myxoid chondrosarcoma Extraskeletal Ewing tumour Desmoplastic small round cell tumour Extra-renal rhabdoid tumour Malignant mesenchymoma Neoplasms with perivascular epithelioid cell differentiation (PEComa) Intimal sarcoma
  7. 7. …… .
  8. 8. Head & neck 5% Superficial trunk 10% Retroperitoneum 15% Viscera 10% Limbs 60%
  9. 9. Adjuvant chemotherapy L = limbs – T = trunk – HN = head & neck – R = retrop – U = uterus – V = viscera gruppo aa n. pz setting regime DFS OS EORTC 77-88 468 L T HN ADM CTX DTIC VCR +13% +7% SSG 81-86 181 L T HN ADM +6% +5% DFCI ECOG IGSC 78-83 168 L T HN R V ADM +13% +3% GOG 73-82 156 U ADM +12% +8% UCLA 81-84 119 L ADM +4% +4% IOR 81-86 77 L ADM +28% +21% NCI 77-81 67 L ADM CTX HDMTX +26% +6% Mayo 75-81 61 L T ADM ActD VCR DTIC -3% 0 Bergonié 81-88 59 L T HN R ADM CTX VCR DTIC +41% +34% MDA 73-76 47 L T ADM ActD CTX VCR -7% NCI 77-81 31 T HN ADM CTX HDMTX +28% +10% NCI 77-81 15 R ADM CTX HDMTX -53%
  10. 11. Localized disease Woll PJ, ASCO Ann meet 2007; #10008
  11. 12. Frustaci S et al, J Clin Oncol 2001;19:1238
  12. 14. 0 epiADM+IFX x 3
  13. 18. LOCALIZED, HIGH-RISK SOFT TISSUE SARCOMAS (STS) OF THE EXTREMITIES AND TRUNK WALL IN ADULTS: THREE VS FIVE CYCLES OF FULL-DOSE ANTHRACYCLINE AND IFOSFAMIDE ADJUVANT CHEMOTHERAPY: A PHASE III RANDOMIZED TRIAL FROM THE ITALIAN SARCOMA GROUP AND SPANISH SARCOMA GROUP Alessandro Gronchi , Sergio Frustaci, Mario Mercuri, Javier Martin, Antonio Lopez-Pousa, Lidia Mariani, Paolo Verderio, Vittorio Quagliuolo, Paolo G. Casali and Piero Picci
  14. 20. Epirubicin 120 mg/m 2 ( ~ DOX 80 mg/m 2 ) + Ifosfamide 9,000 mg/m 2 q 21 days
  15. 21. OS by study arm 70% 69% one-sided 95%: 0.941 (95% CI 0.664 - 1.334) 70% 69% N. at risk Arm A 164 154 138 106 77 43 Arm B 164 157 143 114 77 47
  16. 22. RFS by study arm 61% 60% N. at risk Arm A 156 123 108 74 55 33 Arm B 158 126 108 77 47 31
  17. 23. OS vs previous ISG trial
  18. 24. Sarcomas: spread of disease local isolated extra pulmonary pulmonary
  19. 25. Isolated pulmonary metastatic disease
  20. 27. Advanced disease R ADM 75 mg/sqm + IFX 7.5 g/sqm ADM 75 mg/sqm EORTC Soft Tissue & Bone Sarcoma Group
  21. 28. ADM vs ADM+IFX in advanced STS <ul><li>no. pts. Regimen OR OS </li></ul><ul><li>ECOG , 1993 90 ADM 80 mg/mq 20% = </li></ul><ul><li>88 ADM 60 mg/mq 34% + (NS) </li></ul><ul><li>IFX 7500 mg/mq </li></ul><ul><li>84 ADM 40 mg/mq 32% = </li></ul><ul><li>CDDP 60 mg/mq </li></ul><ul><li>MMC 8 mg/mq </li></ul><ul><li>SWOG/CALGB , 170 ADM 80 mg/mq 17% = </li></ul><ul><li>1993 DTIC 1000 mg/mq </li></ul><ul><li>170 ADM 60 mg/mq 32% = </li></ul><ul><li>IFX 60-7500 mg/mq </li></ul><ul><li>DTIC 1000 mg/mq </li></ul>p<.05
  22. 29. ADM vs ADM+IFX in advanced STS no. pts. Regimen OR OS EORTC , 1991 244 ADM 75 mg/mq 24% = 233 ADM 50 mg/mq 27% = IFX 5000 mg/mq 135 ADM 50 mg/mq 27% = DTIC 750 mg/mq CTX 500 mg/mq VCR 1.5 mg/mq
  23. 30. OR OS Duration of response 218 d (PR) 243 d (CR) Time to progression 240 d (SD) 288 d (PR) 317 d (CR)
  24. 31. …… .
  25. 33. Endometrial stromal sarcoma: progestins, aromatase inhibitors ER PR
  26. 34. Dermatofibrosarcoma: Imatinib COL1A1-PDGFB  PDGFB t(17;22)
  27. 35. Desmoid tumors (aggressive fibromatosis)
  28. 38. L LMS
  29. 40. Stacchiotti S et al, Ann Oncol 2010, 21:1130
  30. 43. Stacchiotti S et al, Mol Cancer Ther 2010;9:1286
  31. 45. PEComas <ul><li>Kidney </li></ul><ul><li>Liver </li></ul><ul><li>Gastrointestinal tract </li></ul><ul><li>Prostate </li></ul><ul><li>Retroperitoneum </li></ul><ul><li>Uterus </li></ul><ul><li>Soft tissue </li></ul><ul><li>Skin </li></ul><ul><li>…… . </li></ul>
  32. 47. Laplante et Sabatini, J Cell Science 2009
  33. 48. SUCCEED study standard CT: best response R Ridaforolimus placebo in advanced STS
  34. 49. Leiomyosarcoma: Dacarbazine 0 DTIC x 2
  35. 50. Dedifferentiated liposa: HD-IFX 0 HD-ci-IFX x 5
  36. 51. Sinovyal sa: HD-IFX 0 +3 mos
  37. 52. Angiosarcoma: taxanes Fata F et al. Cancer 1999; 86: 2034
  38. 54. Angiosarcoma: Gemcitabine 0 +1 mos +4 mos
  39. 55. Leiomyosarcoma: Gemcitabine
  40. 58. A pooled analysis of the final results of the two randomized phase II studies comparing Gemcitabine (G) vs Gemcitabine + Docetaxel (G+D) in patients (pts) with metastatic/relapsed leiomyosarcoma (LMS) F.Duffaud , P. Pautier, B. Bui, M.L Hensley, A.Rey, N.Penel, D.Reinke, A. Le Cesne, J.Y Blay, R.G Maki ESMO Congress, 2010
  41. 59. Pooled analysis – Progression-free survival
  42. 60. Pooled analysis – Progression-free survival
  43. 61. Trabectedin (ET-743)
  44. 62. L -sarcoma liposarcoma leiomyosarcoma
  45. 63. Dedifferentiated liposa 0 ET743 x 16 mos
  46. 64. Uterine leiomyosarcoma 0 ET743 x 3
  47. 65. Lipo sarcoma well diff  dediff myxoid  round cell pleomorphic
  48. 66. well diff  dediff myxoid  round cell pleomorphic
  49. 67. t(12;16)(q13;p11) FUS CHOP 12 16 FUS/CHOP q13 p11
  50. 70. 0 + 1 c +4 c
  51. 72. Mol Cancer Therap 2009;8:449
  52. 73. Synovial sa: Trabectedin
  53. 74. T -STS simple cariotype with reciprocal translocations complex cariotype
  54. 75. Synovial sa t(X;18)(p11;q11) SS18-SSX1 SS18-SSX2 SS18-SSX4 Myxoid liposa t(12;16)(q13;p11) FUS-CHOP t(12;22)(q13;q12) EWS-CHOP Esk. myx. chondrosa t(9;22)(q22;q12) EWS-NR4A3 t(9;17)(q22;q11) RBP56-NR4A3 t(9;15)(q22;q21) TCF12-NR4A3 Fibromyxoid sa t(7;16)(q33;p11) FUS-CREB3L2 t(11;16)(p11;p11) FUS-CREB3L1 Clear cell sa t(12;22)(q13;q12) EWS-ATF1 Dermatofibrosa t(17;22)(q22;q13) COL1A1-PDGFB EFT t(11;22)(q24;q12) EWS-FL1 t(21;22)(q22;q12) EWS-ERG t(7;22)(p22;q12) EWS-ETV1 t(17;22)(q12;q12) EWS-E1AF t(2;22)(q33;q12) EWS-FEV Desmopl. SRCT t(11;22)(p13;q12) EWS-WT1 Alv. rhabdomyosa t(2;13)(q35;q14) PAX3-FOXO1A t(1;13)(p36;q14) PAX7-FOXO1A Alv. soft part sa t(X;17)(p11;q25) TFE3-ASPL Angiomatoid f. histiocytoma t(12;16)(q13;p11) FUS-ATF1 Cong fibrosa t(12;15)(p13;q25) ETV6-NTRK3 Endometrial stromal sa t(7;17)(p15;q21) JAZF1-JJAZ1 Infl. myofibro. t. t(1;2)(q22;p23) TPM3-ALK t(2;19)(p23;p13) TPM4-ALK t(2;17)(p23;q23) CLTC-ALK t(2;2)(p23;q13) RANBP2-ALK
  55. 76. <ul><li>Leiomiyosarcoma : GEM, Trabectedin, DTIC (& Temozolomide), ….. </li></ul><ul><li>Liposarcoma, dediff : Trabectedin, HD-IFX ….. </li></ul><ul><li>Liposarcoma, myxoid : Trabectedin, ….. </li></ul><ul><li>Angiosarcoma : taxanes, GEM, HD-IFX, ….. </li></ul><ul><li>Synovial sa : HD-IFX, Trabectedin, ….. </li></ul><ul><li>MPNST : HD-IFX, VP16 + ….. </li></ul><ul><li>…… . </li></ul>Histology-driven chemotherapy
  56. 77. <ul><li>Dermatofibrosarcoma : Imatinib </li></ul><ul><li>Desmoids : hormones, Imatinib, Sorafenib, ….. </li></ul><ul><li>Alveolar sa : Sunitinib, Cediranib </li></ul><ul><li>Solitary fibrous tumor : Sunitinib, ….. </li></ul><ul><li>Angiosarcoma : Sorafenib </li></ul><ul><li>Inflammatory myofibroblastic tumor : Crizotinib </li></ul><ul><li>LAM and Pecomas : m-TOR inhibitors </li></ul><ul><li>…… . </li></ul>Histology-driven targeted therapy
  57. 78. Gastrointstinal stromal tumors (GIST)
  58. 79. Target therapy in GIST Imatinib SCF
  59. 82. Imatinib chemotherapy OS months
  60. 84. KIT (CD 117)
  61. 85. Lasota J et al, Histopathology 2008 exon 9 (~10%) exon 11 (~70%) exon 13 (~5%) exon 17 (~5 %) PDGFRA (~10%) KIT (~80%) WT (~10%)
  62. 86. KIT exon 9
  63. 87. KIT exon 9 PDGFRA
  64. 89. PDGFRA Corless CL, J Clin Oncol 2005, 23: 5357
  65. 90. GIST in syndromes GIST in children 0 – 18+ yrs
  66. 94. Tumor response
  67. 96. Tumor response: Choi’s criteria 10% 15%
  68. 97. 5 HU 57 HU 39 HU 13 HU 61 HU 15 HU 83 HU 36 HU 57 HU 9 HU 52 HU 3 HU - 2 HU - 18 HU -34 HU 9 HU 5 HU -9 HU -13 HU 3 HU 20 HU 10 HU
  69. 98. PET scan
  70. 99. 0 +3-4 wks +12 mos +18 mos
  71. 100. 50 mg/day, 4 weeks on, 2 weeks off SUNITINIB
  72. 101. Van den Abbeele AD et al, ECCO Ann meet 2005
  73. 102. Sunitinib: interval progression
  74. 103. Imatinib: interval progression
  75. 104. t
  76. 105. BFR14 study R stop Imatinib continue Imatinib Imatinib CR PR SD <ul><li>12 mos </li></ul><ul><li>surgery if feasible </li></ul>
  77. 106. from: ASCO 2009 Virtual Meeting Duffaud F et al, ASCO Ann meet 2009; #10508
  78. 107. Duffaud F et al, ASCO Ann meet 2009; #10508 from: ASCO 2009 Virtual Meeting
  79. 108. Time to secondary resistance…
  80. 110. Secondary resistance
  81. 111. Sunitinib VEGFR-2 VEGFR-1 VEGFR-3 PDGFR-  KIT FLT-3 PDGFR-  RET N H O N H F H 3 C CH 3 N H O N CH 3 CH 3
  82. 113. Negri T al, J Natl Cancer Inst 2009;101:194
  83. 114. Secondary resistance: molecular heterogeneity Liegl B, J Pathol, 2008;216:64
  84. 115. KIT PDGRA VEGFR …… ..
  85. 116. KIT PDGRA VEGFR …… ..
  86. 117. KIT PDGRA VEGFR PI3K AKT mTOR …… ..
  87. 118. KIT PDGRA VEGFR Hsp90 …… ..
  88. 119. GIST: rechallenge with Imatinib 0 +1 mos
  89. 120. Surgery of responding residual disease 
  90. 121. n = 27 n = 8 Gronchi A, Ann Surg 2007; 245:341
  91. 122. Raut CP, J Clin Oncol 2006;24:2325
  92. 124. DeMatteo R et al, Lancet 2009
  93. 125. OS RFS
  94. 126. R OS relapse RFS OS Imatinib Imatinib
  95. 127. R R relapse R relapse Imatinib Imatinib Imatinib
  96. 128. R R relapse R relapse Imatinib Imatinib Imatinib
  97. 129. R R relapse R relapse Imatinib Imatinib Imatinib
  98. 130. R R relapse R relapse Imatinib Imatinib Imatinib
  99. 131. Paolo G. Casali Study Chair & ISG Coordinator Jean-Yves Blay EORTC Coordinator Axel Le Cesne FSG Coordinator Andres Poveda GEIS Coordinator John Zalcberg AGITG Coordinator Martine van Glabbeke Study Statistician Sandrine Marraud Coordinating Physician Anne Kirkpatrick Study Data Manager Intermediate and high risk localized , completely resected, gastrointestinal stromal tumors ( GIST ) expressing KIT receptor: a controlled randomized trial on adjuvant Imatinib mesylate (Glivec ™ ) versus no further therapy after complete surgery
  100. 132. R Imatinib x 2 yrs control
  101. 133. German/Scandinavian trial R Imatinib x 3 yrs Imatinib x 1 yr
  102. 134. Risk stratification Miettinen M. Semin Diagn Pathol 2006; 23: 70 cm M/50HPF gastric jejunal/ ileal duodenal rectal 1 < 2 < 5 0 none 0 none 0 none 0 none 2 >2 < 5 < 5 1.9% very low 4.3% low 8.3% low 8.5% low 3a >5 < 10 < 5 3.6% low 24% moderate 3b >10 < 5 12% moderate 52% high 34% high 57% high 4 < 2 >5 0 50% 54% high 5 >2 < 5 >5 16% moderate 73% high 50% high 52% high 6a >5 < 10 >5 55% high 85% high 6b >10 >5 86% high 90% high 86% high 71% high
  103. 135. Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
  104. 136. Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
  105. 137. Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
  106. 138. Corless C et al, ASCO 2010 (from: ASCO Virtual meeting)
  107. 139. Osteosarcoma
  108. 140. Osteosarcoma
  109. 142. N Engl J Med 1986;314:1600
  110. 143. Cancer 1979; 43: 2163-2177
  111. 144. Cancer 1979; 43: 2163-2177
  112. 145. Goorin AM et al. J Clin Oncol 2003; 21: 1574
  113. 146. Goorin AM et al. J Clin Oncol 2003; 21: 1574
  114. 147. J Clin Oncol 1994;12:2699
  115. 149. J Clin Oncol 1988;6:329
  116. 150. J Natl Cancer Inst 2007;99:112
  117. 153. + IFX + IFX + MTP + MTP + IFX + MTP P<0.05 + IFX + MTP
  118. 154. Ewing’s sarcoma
  119. 155. Ewing’s sarcoma
  120. 157. Cancer 1974;33:384
  121. 158. J Clin Oncol 1990;8:1664
  122. 159. N Engl J Med 2003;348:694
  123. 161. J Clin Oncol 1993;11:1763
  124. 162. Ann Oncol 2010; Nov 8 Epub
  125. 163. Lancet Oncol 2010;11:129
  126. 166. [email_address]

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