Pierre Duvillard

Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma

Survival of metastatic gastroenteropancreatic well-differentiated endocrine carcinoma (GEP WDEC) is not well characterized. We evaluated the long-term outcome and prognostic factors for survival in 118 patients with distant metastases from GEP WDEC. Inclusion criteria were 1) pathological review by a single pathologist according to the present WHO criteria, 2) absence of previous therapy apart from surgery, 3) complete morphological evaluation within 3 months including somatostatin receptor scintigraphy, and 4) follow-up at Gustave-Roussy Institute until death or studys end. Clinical, biological marker, and pathological parameters were analyzed in univariate and multivariate statistical models. Survival after the first complete imaging work-up of the metastatic disease was determined using Kaplan-Meier method. Overall, survival for 5 years after the diagnosis of metastatic disease was 54%. In multivariate analysis, age (hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.01-1.08, P = 0.01), the number of liver metastases (HR: 3.4, 95% CI: 1.4-8.3, P = 0.01), tumor slope (HR: 1.1, 95% CI: 1.0-1.1, P = 0.001), and initial surgery (HR: 0.3, 95% CI: 0.1-0.8, P = 0.01) were predictive of survival. Five-year survival was 100%, 91% (95% CI, 51-98%), 62% (95% CI, 37-83%), and 9% (95% CI, 6-32%) when patients had 0, 1, 2, 3 or more poor prognostic features respectively. This study enables the stratification of metastatic GEP WDEC patients into distinct risk groups. These risk categories can be used to tailor therapeutic approaches and also to design and interpret clinical trials.

A Phase II Study of Irinotecan with 5-Fluorouracil and Leucovorin in Patients with Pretreated Gastroenteropancreatic Well-Differentiated Endocrine Carcinomas

Only a few drugs are active in the treatment of well-differentiated endocrine carcinomas (WDEC). We evaluated the combination of the so-called ‘de Gramont schedule’ and irinotecan in these tumors in a phase II study. Methods: 20 patients were enrolled in the study. The combination regimen included irinotecan, 180 mg/m2 on day 1, followed by 200 mg/m2 folinic acid in a 2-hour infusion, an intravenous 10-min bolus of 400 mg/m2 5-fluorouracil (5FU) and finally 600 mg/m2 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2. Clinical, biological and morphological parameters were assessed by CT every 8 weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3 cases and other sites in 7 cases. Sixteen patients had previously received chemotherapy, and 6 of them had had two lines of treatment. Six patients had previously been treated with chemoembolization. Results: The median number of cycles administered was 8. Grade 3–4 neutropenia was observed in 8 patients, and 1 patient experienced febrile neutropenia. There was no toxicity-related death. No complete symptomatic response was observed in 7 evaluable patients; 4 patients had an objective biological response. One patient achieved a morphological objective response, stabilization was observed in 15, but progression occurred in 3 patients. Median survival was 15 months. Conclusion: The above-mentioned combination of LV5FU2 + irinotecan does not yield major activity in heavily pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant toxicity was observed.

Caractérisation des tumeurs neuroendocrines digestives ou thoraciques

Once the diagnosis of a neuroendocrine tumour has been made, characterisation is an essential step before therapy. It comes before the decision regarding treatment is made. This requires a multidisciplinary team of experts located in specialist centres that currently make up the RENATEN and TENPATH networks. It is directed by knowledge of the location of the primary tumour and anatomical pathological differentiation. The aim of this characterisation step is to highlight factors that may have an impact on the diagnosis and the prognosis or predict the response to treatment.RésuméUne fois le diagnostic de tumeur neuroendocrine (TNE) posé, la caractérisation est une étape essentielle de la prise en charge d’une TNE. Elle précède la décision thérapeutique. Celle-ci fait appel à une expertise multidisciplinaire au sein des centres experts actuellement regroupés au sein des réseaux RENATEN et TENpath. Elle est orientée par la connaissance de la localisation du primitif et la différenciation anatomopathologique. Cette étape de caractérisation a comme objectif: la mise en évidence de facteurs à impact diagnostique, pronostique ou prédictif de la réponse thérapeutique.

Préservation de la fertilité dans les tumeurs borderline de l’ovaire et épithéliales malignes : place, modalités, résultats et limites

Ces dix dernieres annees ont vu beaucoup de travaux evaluant les resultats des traitements conservateurs dans les tumeurs ovariennes. Ce traitement conservateur est la chirurgie de reference chez les patientes ayant une tumeur borderline de l’ovaire (limitee et/ou avec implant[s] peritoneal non invasif). Chez les patientes presentant une tumeur epitheliale maligne de l’ovaire, cette chirurgie conservatrice d’un ovaire et de l’uterus ne peut etre envisagee que chez celles ayant une tumeur d’excellent pronostic (stade IA grade 1, voire grade 2, stade IC grade 1), ayant beneficie d’une chirurgie de stadification adequate et parfaitement suivies.