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 patients with gastrointestinal high-grade neuroendocrine carcinomas (GI-NECs) are lacking; we designed and validated a prognostic score for overall survival (OS). Methods Consecutive patients, diagnosed in five neuroendocrine specialist European Centres were included. Patients were divided into three cohorts: a training cohort (TC), an external validation cohort (EVC) and a prospective validation cohort (PVC). Prognostic factors were identified by using Log-rank test, Cox-regression and logistic regression analyses. The derived score was internally and externally validated. Results Of 395 patients screened, 313 were eligible (TC: 109 patients, EVC: 184 patients and PVC: 20 patients). The derived prognostic score included five variables (presence of liver metastases, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), ECOG performance status (PS) and Ki67). On multivariable analysis, the score was prognostic for OS (HR 1.9, 95%CI 1.5-2.4; p<0.001) and had good discrimination (C-index, 0.76) and calibration (mean error, 0.021; percentile 90, 0.037) in the TC. These results were validated in the EVC and PVC; in which it was able to prognosticate for OS when adjusted for other prognostic variables in the multivariable analysis (HR 1.8 (95%CI 1.3-2.5), p-value 0.001 and HR 4.5 (95%CI 1.9-10.9), p-value 0.001, respectively). The score classified patients into two groups with incremental risk of death: group A (0-2 points; 181 patients (58%); median OS 19.4 months [95%CI 16.1-25.1]) and B (3-6 points; 102 patients (42%); median OS 5.2 months [95%CI 3.6-6.9]). Conclusion The GI-NEC score identifies two distinct patient cohorts; it provides a tool for clinicians when making treatment decisions and may be used as a stratification factor in future clinical trials.