Peritoneal mesothelioma treated by cytoreductive surgery and intra peritoneal hyperthermic perfusion: Clinical and translational study

Abstract

9729 Background: to report the NCI of Milan experience on treating Peritoneal Mesothelioma (PM) with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Secondary endpoints: 1) assessment of potential prognostic factors; 2) test of in vitro PM sensitivity to chemotherapies; 3) development of a gene therapy approach. Methods: Thirty eight PM patients underwent 40 consecutive procedures. Mean follow-up was 18,7 mths. 34 (89%) cases had malignant epithelioid disease. Twenty one (53%) cases received preoperative chemotherapy. The IPHP was performed with closed abdomen technique with cisplatin+mitomycin-C or cisplatin+doxorubicin through a heart-lung pump for 60 or 90 minutes at 42.5° C. Potential prognostic biological markers were evaluated on surgical 19 PM specimens. PM in vitro drug sensitivity was evaluated on primary cultures derived from surgical specimens. We established new PM cell lines for the development of a gene therapy approach, which aimed at the inhibition of cell survival factors. Results: 5-year overall and progression free survivals were 70% and 49%, respectively. The operative morbidity GIII, mortality and toxicity GIII/IV rates were 20%, 0% and 10%, respectively. PM cells largely expressed anti-apototic proteins belonging to bcl-2 and IAP family; most of the cases were negative for the expression of the pro-apototic factor SMAC/diablo. Reactivation of telomerase was found in 17/19 cases, which were positive for the expression of the hTERT catalytic subunit of the enzyme. The assessment of sensitivity profile of 7 PM primary cultures to a panel of drugs found a variable response rate for the different compounds. Conclusions: CRS+IPHP seems consistent with a potentially effective treatment for selected PM patients. Apoptosis related markers presented an apparent correlation with PM tumor cell biology, but the their prognostic significance is still undefined. Further definition of drug sensitivity profile and the development gene therapies will provide a possible biological rationale for the design of new clinical treatments. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AIRC (Italian Association of Cancer Research)