المؤلفون: de Mestier, Louis, Lamarca, Angela, Hernando, Jorge, Zandee, Wouter, Alonso-Gordoa, Teresa, Perrier, Marine, Walenkamp, Annemieke M E, Chakrabarty, Bipasha, Landolfi, Stefania, Van Velthuysen, Marie-Louise F, Kats-Ugurlu, Gursah, Carminoa, Alejandra, Ronot, Maxime, Manoharan, Prakash, Garcia-Alvarez, Alejandro, Brabander, Tessa, García Gómez-Muriel, María Isabel, Cadiot, Guillaume, Couvelard, Anne, Capdevilla, Jaume, Pavel, Marianne E, Cros, Jerome

المصدر: de Mestier , L , Lamarca , A , Hernando , J , Zandee , W , Alonso-Gordoa , T , Perrier , M , Walenkamp , A M E , Chakrabarty , B , Landolfi , S , Van Velthuysen , M-L F , Kats-Ugurlu , G , Carminoa , A , Ronot , M , Manoharan , P , Garcia-Alvarez , A , Brabander , T , García Gómez-Muriel , M I , Cadiot , G , Couvelard , A , Capdevilla , J , Pavel , M E & Cros , J 2021 , ' Treatment ....

مصطلحات موضوعية: neuroendocrine tumors, grade 3, treatment, prognosis, GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS, ENETS CONSENSUS GUIDELINES, G3, NEOPLASMS, CARCINOMA, CHEMOTHERAPY, PREDICTORS, NEN

الوصف: 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.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/b3550a9f-5cc9-4999-a446-185bc5c825dfTest

الإتاحة: https://doi.org/10.1530/ERC-21-0109Test
https://hdl.handle.net/11370/b3550a9f-5cc9-4999-a446-185bc5c825dfTest
https://research.rug.nl/en/publications/b3550a9f-5cc9-4999-a446-185bc5c825dfTest
https://pure.rug.nl/ws/files/644094439/1479_6821_ERC_21_0109.pdfTest

المؤلفون: Pozas, Javier¹ (AUTHOR), Alonso-Gordoa, Teresa¹ (AUTHOR), Román, Maria San¹ (AUTHOR), Santoni, Matteo² (AUTHOR), Thirlwell, Chrissie³ (AUTHOR), Grande, Enrique⁴ (AUTHOR), Molina-Cerrillo, Javier¹ (AUTHOR) javier.molinace@gmail.com

المصدر: BBA - Reviews on Cancer. Sep2022, Vol. 1877 Issue 5, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *THERAPEUTICS, *PROTEIN-tyrosine kinase inhibitors, *PEPTIDE receptors, *EPIGENETICS, *NEUROENDOCRINE tumors

مستخلص: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies with distinct prognosis based on primary tumor localization, grade, stage and functionality. Surgery remains the only curative option in localized tumors, but systemic therapy is the mainstay of treatment for patients with advanced disease. For decades, the therapeutic landscape of GEP-NETs was limited to chemotherapy regimens with low response rates. The arrival of novel agents such as somatostatin analogues, peptide receptor radionuclide therapy, tyrosine kinase inhibitors or mTOR-targeted drugs, has changed the therapeutic paradigm of GEP-NETs. However, the efficacy of these agents is limited in time and there is scarce knowledge of optimal treatment sequencing. In recent years, massive parallel sequencing techniques have started to unravel the genomic intricacies of these tumors, allowing us to better understand the mechanisms of resistance to current treatments and to develop new targeted agents that will hopefully start an era for personalized treatment in NETs. In this review we aim to summarize the most relevant genomic aberrations and signaling pathways underlying GEP-NET tumorigenesis and potential therapeutic strategies derived from them. • Gastro-entero-pancreatic NETs (GEP-NETs) comprise tumors originating from the gastro-intestinal tract and the pancreas. • pNET and siNET are genetic and epigenetic different entities being defined by distinct oncogenic molecular pathways. • Whole exome sequencing has opened the door to new treatment strategies in these rare tumors. • Integration of genetic and epigenetic data is becoming essential to guide clinical decisions in this setting of patients. [ABSTRACT FROM AUTHOR]