S. Leboulleux

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.

Antiangiogenic Tyrosine Kinase Inhibitors: Occurrence and Risk Factors of Hemoptysis in Refractory Thyroid Cancer

BACKGROUND Antiangiogenic tyrosine kinase inhibitors (TKIs) are the mainstay of advanced thyroid cancer (TC) treatment. Concern is rising about TKI-related toxicity. OBJECTIVE To determine the incidence and to investigate the risk factors of hemoptysis in TC patients during TKI treatment. METHODS We analyzed consecutive TC patients treated with TKI in our center between 2005 and 2013 and performed an independent review of computed tomography scan images for airway invasion assessment. Occurrence of grade 1-2 or grade 3-5 hemoptysis according to Common Terminology Criteria for Adverse Events version 4.03 and risk factors for hemoptysis were investigated. RESULTS A total of 140 patients (89 males; median age, 52 y) with medullary (56%), differentiated (33%), and poorly differentiated (11%) TC were enrolled. Thyroidectomy±neck dissection was performed in 123 patients and neck/mediastinum external-beam radiotherapy in 41 (32% with therapeutic purpose and 68% with adjuvant purpose). Patients received from 1 to 4 lines of TKI (median 1). Median follow-up was 24 months. Airway invasion was found in 65 (46%) cases. Hemoptysis occurred in 9 patients: grade 1-2 in 7 cases (5%) and grade 3-5 in 2 (1.4%) cases (fatal in 1). Hemoptysis was associated with presence of airway invasion (P = .04), poorly differentiated pathology (P = .03), history of therapeutic external-beam radiotherapy (P = .003), and thyroidectomy without neck dissection (P = .02). CONCLUSION Airway invasion, poorly differentiated pathology, therapeutic external-beam radiotherapy, and thyroidectomy without neck dissection are associated with and increased risk of hemoptysis in TC patients during antiangiogenic TKI treatment. Further research is needed to confirm this data and to sort out interactions between these risk factors. A careful assessment of airway invasion is mandatory before TKI introduction.

Resection margins and prognosis in locally invasive thyroid cancer.

Invasive thyroid cancer is rare, and the extent of surgery controversial. The purpose of this study was to present and evaluate therapeutic prognostic factors.

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.

Imagerie des tumeurs primitives du peritoine

Objectifs Connaitre les principales tumeurs primitives du mesentere et du peritoine. Connaitre leur diagnostic differentiel. Decrire l’imagerie des tumeurs primitives du mesentere et du peritoine. Connaitre les approches therapeutiques, en particulier chirurgicales, et les attentes des chirurgiens concernant le compte rendu radiologique. Points cles Les principales tumeurs primitives solides du mesentere sont la tumeur desmoide, la tumeur de castelman et les tumeurs conjonctives ou mesenchymateuses. Les principales tumeurs primitives peritoneales sont pseudomyxome, le mesotheliome, la carcinose sereuse papillaire et la tumeur desmo-plastique a petites cellules. Le principal diagnostic differentiel est la carcinose peritoneale. Resume Le peritoine est le siege d’atteintes tumorales et inflammatoires frequentes. Si les atteintes tumorales secondaires sont les plus frequentes, les masses tumorales primitives ne sont pas exceptionnelles. L’imagerie, en particulier le scanner, joue un role primordial dans le diagnostic positif et differentiel de ces masses ainsi que leur bilan d’extension. Devant une tumeur mesenterique tissulaire il faut evoquer le plus souvent une tumeur desmoide ou une tumeur conjonctive ou mesenchymateuse qui peut etre benigne ou maligne. Devant une tumeur du peritoine il faut evoquer un pseudomyxome, un mesotheliome, une carcinose sereuse papillaire chez une femme sans tumeur ovarienne et la tumeur desmoplastique a petites cellules chez un jeune homme.

Chimioembolisation arterielle de metastases hepatiques de corticosurrenalomes

Objectifs Evaluer la tolerance et l’efficacite de la chimioembolisation arterielle hepatique (CHE) chez des patients ayant des metastases hepatiques de corticosurrenalome (MHCS). Materiels et methodes Vingt-neuf patients consecutifs (24 femmes et 5 hommes) avec 103 MHCS evolutives ont ete traites par CHE (Cisplatine (1-2 mg/kg) + Lipiodol (lOcc) + Spongel) entre juin 1995 et aout 2005. Les reponses hormonales et morphologiques ont ete evaluees tous les 1-3 mois. La reponse morphologique etant evaluee par les criteres RECIST et la prise de lipiodol. Resultats Cinquante CHE ont ete realisees. Apres 2-32 mois (mediane = 9,6) une reponse partielle a ete obtenue sur 26 metastases, il y avait 13 reponses mineures, 42 etaient stables et 22 progressaient. Six patients ont eu une reponse partielle, 16 avaient une maladie stable et 7 une progression. Soixante-dix MHCS/103 avaient une fixation lipiodolee superieure a 50 %. La secretion hormonale avait diminue chez 9/16 patients secreteurs. Six patients etaient encore en vie 5 a 44,5 mois apres la premiere CHE (mediane = 19,6) ; tandis que 23 etaient decedes entre 2 et 51 mois (mediane = 10,8). Conclusion Chez les patients ayant des MHCS, la CHE permet un taux de reponse cumulee et de stabilisation de 76 %. Les meilleures reponses concernent les metastases inferieures a 3 cm, incitant a utiliser ce traitement precocement au cours de la maladie.