padova, 30 maggio 2008 carlo riccardo rossi unità melanoma e sarcomi clinica chirurgica ii -...
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Padova, 30 maggio 2008
Carlo Riccardo RossiUnità Melanoma e Sarcomi
Clinica Chirurgica II - Università di Padova
Ha uno spazio la chirurgia Ha uno spazio la chirurgia nella sarcomatosi retroperitoneale?nella sarcomatosi retroperitoneale?
Aggiornamento in tema di Sarcomi delle Parti Molli e Aggiornamento in tema di Sarcomi delle Parti Molli e GISTGIST
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SPREAD OF SOFT TISSUE SARCOMAS (STS) OR GISTs
THROUGHTOUT THE ABDOMEN (WITHOUT DISTANT METASTASES)
DEFINITIONDEFINITION
Peritoneal sarcomatosis
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RETROPERITONEAL SARCOMASLOCAL RECURRENCE AND SURVIVAL
Author Year LocalRecurrence (%)
5 yrs Survival (%)
Lewis JJ et al 1998 24 54
Stoeckle E et al 2001 48 46
Gilbeau L et al 2002 51 60
Gronchi A et al 2004 44 54
Ballo MT et al 2006 43 44
Peritoneal sarcomatosis
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GISTs
LOCAL RECURRENCE AND SURVIVAL
Author Year LocalRecurrence (%)
5 yrs Survival
Eilber FC et al 2000 48 31
De Matteo RP et al 2000 40 54
Crosby JA et al 2001 43 41
Pierie JP et al 2001 60 42
Before Imatinib advent
Peritoneal sarcomatosis
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TREATMENT:STATE OF THE ART
•Systemic
•Locoregional
Peritoneal sarcomatosis
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• Antracyclin +/- ifosfamide
• Gemcitabine +/- docetaxel leiomyosarcoma
• Trabectedine (ET-743) liposarcomaleiomyosarcoma
• Imatinib
STANDARD TREATMENT (SYSTEMIC CHEMOTHERAPY + SURGERY)
Response rate: 20-40%
Median survival 12-24 mos
Response Rate: 50-85%
Overall 2 yr survival: 71%
Retroperitoneal Sarcomas
GISTs
Peritoneal sarcomatosis
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SYSTEMIC CHEMOTHERAPY + PALLIATIVE SURGERY
MD ANDERSON CANCER CENTER EXPERIENCE
Bilimoria et al., Cancer 2001
N° of pts: 51
Recurrence rate: 72 %
Median Survival: 22 mos
Peritoneal sarcomatosis
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AggressiveCytoreductiveSurgery ±
LOCOREGIONAL TREATMENT
EPIC
HIPEC
Postoperative adhesionsLow drug penetration 1-3mm
Barriers to effective treatment
(Early Post-operative IntraPeritonealChemiotherapy)
(Hyperthermic IntraPeritoneal Chemotherapy)
Peritoneal sarcomatosis
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CYTORIDUCTIVE SURGERYCYTORIDUCTIVE SURGERY
Peritoneal sarcomatosis
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BodyVd, [drug]
Peritoneal cavityVd, [drug]
ClearanceK
Intercompartmental
Transport (IT)
K > IT = ADVANTAGEHigh MW
High Syst Cl
INTRAPERITONEAL CHEMOTHERAPYINTRAPERITONEAL CHEMOTHERAPY
RATIONALERATIONALE
Peritoneal sarcomatosis
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HIPEC TECHNIQUEHIPEC TECHNIQUE
Peritoneal sarcomatosis
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LOCOREGIONAL TREATMENT:EPIC/HIPEC
THE WASHINGTON CANCER INSTITUTE
N° of pts: 43Recurrence rate: 100%Median Survival: 20 months
Berthet B et al. Eur J Cancer, 1999
Peritoneal sarcomatosis
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Eilber FC et al, Ann Surg Oncol, 1999
UCLA MEDICAL CENTER
N° of pts: 35Recurrence rate: 48%Median Survival: 24 mos
LOCOREGIONAL TREATMENT: EPIC
Peritoneal sarcomatosis
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INSTITUT GUSTAVE ROUSSY
Bonvalot S et al, EJSO, 2005
N° of pts: 38
Recurrence rate: 100%
Overall Survival: 29 months
LOCOREGIONAL TREATMENT: EPIC
Peritoneal sarcomatosis
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LOCOREGIONAL TREATMENT: HIPEC
Rossi CR et al, Cancer 2002
DOXO: 15.25 mg/l
CDDP: 43.00 mg/lRESULTS
PADOVA UNIVERSITY
Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy
(Phase I study)
Peritoneal sarcomatosis
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perfusate
plasma
Open symbols = DOXO
Filled symbols = CDDP
Rossi et al, Cancer 2002
LOCOREGIONAL TREATMENT (HIPEC):PHARMACOKINETICS OF DOXO
Peritoneal sarcomatosis
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LOCOREGIONAL TREATMENT (HIPEC): PHARMACOKINETICS OF DOXO
Rossi et al., Cancer 2002
PERITONEUM MUSCLE FAT TUMOR
Peritoneal sarcomatosis
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LOCOREGIONAL TREATMENT (HIPEC):SITILO* EXPERIENCE
(Phase II study)
CC0CC1
68%32%
MORBMORT
33%0%
MEAN FU 28 mo
PTS: 60
HISTOL: LIPO 20
UTERUS 13
GIST 14
OTHER 13
GRADING: G1 23
G2-3 37
* ITALIAN SOCIETY FOR LOCOREGIONAL TREATMENT OF CANCER
Peritoneal sarcomatosis
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N° of pts: 60
Recurrence rate: 52%
Overall Survival: 34 months
Rossi et al, Cancer 2004
LOCOREGIONAL TREATMENT (HIPEC):SITILO EXPERIENCE
(Phase II study)
Peritoneal sarcomatosis
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• PREOPERATIVE EVALUATION
• ELEGIBILITY
• METHODOLOGY
• FOLLOW – UP
• FUTURE INVESTIGATIONS
RESULTS OF THE DISEASE CONSENSUS VOTING
Peritoneal sarcomatosis
5th International Workshop on Peritoneal Surface Malignancy, Milano 2006
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YES 66,67%
NO 33,33%
YES 50,00%
NO 50,00%
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?
YES 66,67%
NO 33,33%
With regard to the GIST model, may we foresee a role for HIPEC in patient non responsive to targeted therapies?
Results of the disease consensus votingELIGIBILITY
Peritoneal sarcomatosis
5th International Workshop on Peritoneal Surface Malignancy, Milano 2006
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Investigational only 58,33%
Suitable for individual clinical use in selected patients
41,67%
Only for palliation 33,33%
For Locoregional Control 66,67%
For Improvement on survival 0,00%
Results of the disease consensus votingELIGIBILITY
At the time of primary tumor treatment
9,09%
At the time of recurrence 72,73%
Both 18,18%
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?
Peritoneal sarcomatosis
5th International Workshop on Peritoneal Surface Malignancy, Milano 2006
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cc-0:
Yes No
100,00% 0,00%
cc-1:
Yes No
62,50% 37,50%
YES 25,00%
NO 75,00%
Results of the disease consensus votingSTATE OF THE ART OF METHODOLOGY
YES 91,67%
NO 8,33%
YES 25,00%
NO 75,00%
YES 27,27%
NO 72,73%
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
Peritoneal sarcomatosis
5th International Workshop on Peritoneal Surface Malignancy, Milano 2006
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Single 0,00%
Combination 100,00%
1 cisplatin+mitomycin-C 0,00%
2 cisplatin+doxorubicin 100,00%
3 other 0,00%
Would you consider single agent or combination HIPEC best?
What drugs would be best to use HIPEC combination agent
Results of the disease consensus votingSTATE OF THE ART OF METHODOLOGY
Peritoneal sarcomatosis
5th International Workshop on Peritoneal Surface Malignancy, Milano 2006
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YES 91,67%
NO 8,33%
Results of the disease consensus votingFUTURE INVESTIGATIONS SHOULD BE
DIRECTED AT
YES 91,67%
NO 8,33%
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
Peritoneal sarcomatosis
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• 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
CONCLUSIONS
Peritoneal sarcomatosis