Design and Validation of the GI-NEC Score to Prognosticate Overall Survival in Patients with High-Grade Gastrointestinal Neuroendocrine Carcinomas

Background: Prognostic markers for risk-stratification of pts with GI-NECs are lacking. We aimed to externally validate our previously-designed prognostic score (Training Cohort [TC]) derived from 109 pts (Lamarca et al, ASCO 2015). The score included five variables (presence of liver metastases, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), ECOG performance status (PS) and Ki67) and was able to prognosticate overall survival (OS). Methods: Pts diagnosed with GI-NECs were identified retrospectively from 5 European centres (April’00 – Dec’15); pts with data for all 5 variables identified from the TC were eligible for the Validation Cohort (VC). To externally validate the score (power: 80% and two-tailed α-error: 0.05), a minimum of 82 pts was required. The primary end-point was OS; Cox regression and Kaplan-Meier estimates were applied; and univariate/multivariable analyses performed. Results: Of 209 pts identified; 178 were eligible. The median follow-up time was 11.8 months (range 0.2-167.4); 121 pts (68%) had died at time of the analysis. Median age: 58.7 yrs (range 22.2-85.5); 62% were male, 81% metastatic, 18% foregut, 3% midgut, 41% pancreas, 17% hindgut and 21% unknown primary. The median Ki67 was 55% (21-100), ECOG PS 0: 35%, 1: 46%; 66% received chemotherapy. The baseline median ALK and LDH were 133 IU/l (30-2363) and 347 IU/l (107-3786), respectively; there were significant differences (p < 0.05) in Ki67 and LDH between TC and VC. The estimated median OS was 16.1 months (95%CI 14.6-19.4). Both score (p < 0.001) and stage (p = 0.002) were significant in the univariate analysis. On multivariable analysis (adjusted for stage), the score was prognostic for OS (HR 1.4, 95%CI 1.1-1.6; p = 0.001) validating previous TC results. The score classified pts into different groups with incremental risk of death: groups A/B (0-2 points; 117 pts (66%); median OS 20.7 months [95%CI 17.2-28.1]) and C/D (3-6 points; 61 pts (34%); median OS 8.1 months [95%CI 4.8-9.4]). Conclusions: This international external series validates the capability of our prognostic score to predict OS in pts with GI-NECs; these results may inform clinical decision-making and trial design.