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Padova, 30 maggio 2008

Aggiornamento in tema di Sarcomi delle Parti Molli e GIST. Ha uno spazio la chirurgia nella sarcomatosi retroperitoneale?. Carlo Riccardo Rossi Unità Melanoma e Sarcomi Clinica Chirurgica II - Università di Padova. Padova, 30 maggio 2008. Peritoneal sarcomatosis. DEFINITION.

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Padova, 30 maggio 2008

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  1. Aggiornamento in tema di Sarcomi delle Parti Molli e GIST Ha uno spazio la chirurgia nella sarcomatosi retroperitoneale? Carlo Riccardo Rossi Unità Melanoma e Sarcomi Clinica Chirurgica II - Università di Padova Padova, 30 maggio 2008

  2. Peritoneal sarcomatosis DEFINITION • SPREAD OF SOFT TISSUE SARCOMAS (STS) OR GISTs • THROUGHTOUT THE ABDOMEN (WITHOUT DISTANT METASTASES)

  3. Peritoneal sarcomatosis RETROPERITONEAL SARCOMAS LOCAL RECURRENCE AND SURVIVAL

  4. Peritoneal sarcomatosis GISTs LOCAL RECURRENCE AND SURVIVAL Before Imatinib advent

  5. Peritoneal sarcomatosis • TREATMENT: • STATE OF THE ART • Systemic • Locoregional

  6. Peritoneal sarcomatosis STANDARD TREATMENT (SYSTEMIC CHEMOTHERAPY + SURGERY) • Antracyclin +/- ifosfamide • Gemcitabine +/- docetaxelleiomyosarcoma • Trabectedine (ET-743) liposarcoma • leiomyosarcoma • Imatinib Retroperitoneal Sarcomas Response rate: 20-40% Median survival 12-24 mos GISTs Response Rate: 50-85% Overall 2 yr survival: 71%

  7. Peritoneal sarcomatosis SYSTEMIC CHEMOTHERAPY + PALLIATIVE SURGERY MD ANDERSON CANCER CENTER EXPERIENCE • N° of pts: 51 • Recurrence rate: 72 % • Median Survival: 22 mos Bilimoria et al., Cancer 2001

  8. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT • Aggressive • Cytoreductive • Surgery ± • Barriers to effective treatment • Postoperative adhesions • Low drug penetration 1-3mm (Early Post-operative IntraPeritoneal Chemiotherapy) EPIC (Hyperthermic IntraPeritoneal Chemotherapy) HIPEC

  9. Peritoneal sarcomatosis CYTORIDUCTIVE SURGERY

  10. Peritoneal sarcomatosis INTRAPERITONEAL CHEMOTHERAPY RATIONALE Body Vd, [drug] K Clearance Intercompartmental Transport (IT) Peritoneal cavity Vd, [drug] High MW K > IT = ADVANTAGE High Syst Cl

  11. Peritoneal sarcomatosis HIPEC TECHNIQUE

  12. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT: EPIC/HIPEC • N° of pts: 43 • Recurrence rate: 100% • Median Survival: 20 months THE WASHINGTON CANCER INSTITUTE Berthet B et al. Eur J Cancer, 1999

  13. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT: EPIC UCLA MEDICAL CENTER • N° of pts: 35 • Recurrence rate: 48% • Median Survival: 24 mos Eilber FC et al, Ann Surg Oncol, 1999

  14. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT: EPIC • N° of pts: 38 • Recurrence rate: 100% • Overall Survival: 29 months INSTITUT GUSTAVE ROUSSY Bonvalot S et al, EJSO, 2005

  15. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT:HIPEC • Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy • (Phase I study) PADOVA UNIVERSITY DOXO: 15.25 mg/l CDDP: 43.00 mg/l RESULTS Rossi CR et al, Cancer 2002

  16. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT (HIPEC):PHARMACOKINETICS OF DOXO perfusate plasma Open symbols = DOXO Filled symbols = CDDP Rossi et al, Cancer 2002

  17. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT (HIPEC): PHARMACOKINETICS OF DOXO PERITONEUM MUSCLE FAT TUMOR Rossi et al., Cancer 2002

  18. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT (HIPEC):SITILO* EXPERIENCE(Phase II study) • PTS: 60 • HISTOL: LIPO 20 • UTERUS 13 • GIST 14 • OTHER 13 • GRADING: G1 23 • G2-3 37 * ITALIAN SOCIETY FOR LOCOREGIONAL TREATMENT OF CANCER

  19. Peritoneal sarcomatosis LOCOREGIONAL TREATMENT (HIPEC): SITILO EXPERIENCE (Phase II study) • N° of pts: 60 • Recurrence rate: 52% • Overall Survival: 34 months Rossi et al, Cancer 2004

  20. Peritoneal sarcomatosis RESULTS OF THE DISEASE CONSENSUS VOTING • PREOPERATIVE EVALUATION • ELEGIBILITY • METHODOLOGY • FOLLOW – UP • FUTURE INVESTIGATIONS 5th International Workshop on Peritoneal Surface Malignancy, Milano 2006

  21. Peritoneal sarcomatosis Results of the disease consensus voting ELIGIBILITY With regard to the non-GIST sarcomas, may we foresee a role for HIPEC in the era of molecularly targeted therapies? With regard to the GIST model, may we foresee a role for HIPEC in the era of molecularly targeted therapies? With regard to the GIST model, may we foresee a role for HIPEC in patient non responsive to targeted therapies? 5th International Workshop on Peritoneal Surface Malignancy, Milano 2006

  22. Peritoneal sarcomatosis Results of the disease consensus voting ELIGIBILITY Referring to retroperitoneal sarcomas, pelvic sarcomas, GIST, is there any clinical presentation in which abdominal sarcomatosis could be treated today with HIPEC outside a clinical study? In other words, as of today, should we consider HIPEC: As of today's knowledge, which is the selective contribution of cytoreductive surgery, antiblastic perfusion and hyperthermia to the potential efficacy of HIPEC, if any, in abdominal sarcomatosis? With regard to non-GIST sarcomas, which timing for HIPEC may we foresee within combined approaches incorporating pre/post-operative chemotherapy? 5th International Workshop on Peritoneal Surface Malignancy, Milano 2006

  23. Peritoneal sarcomatosis Results of the disease consensus voting STATE OF THE ART OF METHODOLOGY 1-SURGERY: Definition of Complete Cytoreductive Surgery • Is there a role for maximal palliative cytoreduction in not amenable to radical surgery? • Is it sufficient a limited peritonectomy to the affected area? • Is it indicated a complete parietal peritonectomy even in case of limited affected area? 2- HIPEC: Role of HIPEC in Palliative/inoperable 5th International Workshop on Peritoneal Surface Malignancy, Milano 2006

  24. Peritoneal sarcomatosis Results of the disease consensus voting STATE OF THE ART OF METHODOLOGY Would you consider single agent or combination HIPEC best? What drugs would be best to use HIPEC combination agent 5th International Workshop on Peritoneal Surface Malignancy, Milano 2006

  25. Peritoneal sarcomatosis Results of the disease consensus voting FUTURE INVESTIGATIONS SHOULD BE DIRECTED AT Do you think it is necessary to perform a large trial in order to identify the role of CRS + HIPEC in patients with Peritoneal Sarcomatosis? Should the patients be randomized to CRS+HIPEC vs. CRS alone 5th International Workshop on Peritoneal Surface Malignancy, Milano 2006

  26. Peritoneal sarcomatosis CONCLUSIONS • Chemotherapy +/- surgery +/- radiotherapy is the standard palliative treatment for sarcomatosis and locally advanced GISTs • Median survival after standard treatment is 12-24 months for sarcomatosis before Imatinib (including GISTs) • Imatinib improves median survival up to 58 months in GISTs (locoregional treatment excluded at present) • There is no sufficient evidence supporting the locoregional treatment of sarcomatosis with surgery associated to EPIC/HIPEC • Cytoreductive surgery and HIPEC should be further investigated in sarcomatosis confined to the peritoneum or imatinib resistant GISTs

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