There is no standardized treatment for grade 3 neuroendocrine tumors (G3 NETs). We aimed to describe the treatments received in patients with advanced G3 NETs and compare their efficacy. Patients with advanced digestive G3 NETs treated between 2010 and 2018 in seven expert centers were retrospectively studied. Pathological samples were centrally reviewed, and radiological data were locally reviewed. We analyzed RECIST-defined objective response (OR), tumor growth rate (TGR) and progression-free survival (PFS) obtained with first- (L1) or second-line (L2) treatments. We included 74 patients with advanced G3 NETs, mostly from the duodenal or pancreatic origin (71.6%), with median Ki-67 of 30%. The 126 treatments (L1 = 74; L2 = 52) included alkylating-based (n = 32), etoposide-platinum (n = 22) or adenocarcinoma-like (n = 20) chemotherapy, somatostatin analogs (n = 21), targeted therapies (n = 22) and liver-directed therapies (n = 7). Alkylating-based chemotherapy achieved the highest OR rate (37.9%) compared to other treatments (multivariable OR 4.22, 95% CI (1.5–12.2); P = 0.008). Adenocarcinoma-like and alkylating-based chemotherapies showed the highest reductions in 3-month TGR (P < 0.001 and P = 0.008, respectively). The longest median PFS was obtained with adenocarcinoma-like chemotherapy (16.5 months (9.0–24.0)) and targeted therapies (12.0 months (8.2–15.8)), while the shortest PFS was observed with somatostatin analogs (6.2 months (3.8–8.5)) and etoposide-platinum chemotherapy (7.2 months (5.2–9.1)). Etoposide-platinum CT achieved shorter PFS than adenocarcinoma-like (multivariable HR 3.69 (1.61–8.44), P = 0.002) and alkylating-based chemotherapies (multivariable HR 1.95 (1.01–3.78), P = 0.049). Overall, adenocarcinoma-like and alkylating-based chemotherapies may be the most effective treatments for patients with advanced G3 NETs regarding OR and PFS. Etoposide-platinum chemotherapy has poor efficacy in this setting.
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Louis de Mestier, Angela Lamarca, Jorge Hernando, Wouter Zandee, Teresa Alonso-Gordoa, Marine Perrier, Annemiek ME Walenkamp, Bipasha Chakrabarty, Stefania Landolfi, Marie-Louise F Van Velthuysen, Gursah Kats-Ugurlu, Alejandra Caminoa, Maxime Ronot, Prakash Manoharan, Alejandro Garcia-Alvarez, Tessa Brabander, María Isabel García Gómez-Muriel, Guillaume Cadiot, Anne Couvelard, Jaume Capdevila, Marianne E Pavel, and Jérôme Cros
Nicola Fazio, Lorenzo Gervaso, Thorvardur R Halfdanarson, Mohamad Sonbol, Rachel A Eiring, Sara Pusceddu, Natalie Prinzi, Benedetta Lombardi Stocchetti, Simona Grozinsky-Glasberg, David J. Gross, Thomas Walter, Patrick Robelin, Catherine Lombard-Bohas, Samuele Frassoni, Vincenzo Bagnardi, Lorenzo Antonuzzo, Clotilde Sparano, Sara Massironi, Fabio Gelsomino, Alberto Bongiovanni, Nicoletta Ranallo, Salvatore Tafuto, Maura Rossi, Mauro Cives, Kakil Ibrahim Rasul, Hytham Hamid, Alessandra Chirco, Michela Squadroni, Anna La Salvia, Jorge Hernando, Johannes Hofland, Anna Koumarianou, Sabrina Boselli, Darina Tamayo, Cristina Mazzon, Manila Rubino, and Francesca Spada
Preliminary results regarding 85 patients of the INTENSIVE study have been published in 2021. Now we are reporting the 2-year analysis. We conducted a retrospective/prospective worldwide study on patients with neuroendocrine neoplasms (NENs) and a molecularly proven SARS-CoV-2 positivity. Here we are reporting data from consecutive patients enrolled between June 01, 2020, and May 31, 2022. Among the 118 contacted centers, 25 were active to enroll and 19 actively recruiting at the time of data cut-off for a total of 280 patients enrolled. SARS-CoV-2 positivity occurred in 47.5% of patients in 2020, 35.1% in 2021 and 17.4% in 2022. Median age at COVID-19 diagnosis was 60 years. Well differentiated tumors, non-functioning, metastatic stage and gastroenteropancreatic (GEP) primary site represented most of NENs. COVID-19-related pneumonia occurred in 22.8% of the total, with 61.3% of them requiring hospitalization; 11 patients (3.9%) needed sub-intensive or intensive care unit therapies and 14 patients died (5%), in 11 cases (3.9%) directly related to COVID-19. Thoracic and other NEN primary site were associated with hospitalization for COVID-19 and with sub-intensive or intensive care. A significant decrease in both hospitalization and pneumonia occurred in 2022 versus 2020. In our largest series of NEN patients with COVID-19, the NEN population is similar to the general population regardless of COVID-19. However, older age, non-GEP primary sites and diabetes mellitus should be carefully considered for increased COVID-19 morbidity and mortality. Relevant information could be derived by integrating our results with NENs patients included in other cancer patients and COVID-19 registries.