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Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study

AuthorsCarmona-Bayonas, A.; Jiménez-Fonseca, Paula; Lamarca, Ángela; Barriuso, Jorge CSIC ORCID ; Castaño, Ángel; Benavent, Marta; Alonso, Vicente; Riesco-Martínez, María del Carmen; Alonso Gordoa, Teresa; Custodio, Ana; Sánchez Canovas, Manuel; Hernando Cubero, Jorge; Lopez, Carlos; Lacasta, Adelaida; Fernández Montes, Ana; Marazuela-Azpiroz, Mónica; Crespo, Guillermo; Escudero, Pilar; Díaz, José Ángel; Feliciangeli, Eduardo; Gallego, Javier; Llanos, Marta; Segura, Ángel; Vilardell, Felip; Percovich, Juan Carlos; Grande, Enrique; Capdevila, Jaume; Valle, Juan W.; García-Carbonero, Rocío CSIC ORCID
Issue Date1-Oct-2019
PublisherAmerican Society of Clinical Oncology
CitationJournal of Clinical Oncology 37(28): 2571-2580 (2019)
Abstract[Purpose] Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients.
[Patient and methods] We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom).
[Results] We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively.
[Conclusion] The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.
Publisher version (URL)https://doi.org/10.1200/JCO.19.00980
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