Abstract
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). Consecutive patients diagnosed in five neuroendocrine specialist European centers 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 log-rank test, Cox-regression, and logistic regression analyses. The derived score was internally and externally validated. All statistical tests were two-sided. 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), Eastern Cooperative Oncology Group performance status (ECOG PS), and Ki67. In multivariable analysis, the score was prognostic for OS (hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.47 to 2.35, P < .001) and had good discrimination (C-index = 0.76) and calibration (mean error = 0.021, 90th percentile = 0.037) in the TC. These results were validated in the EVC and PVC, in which our score was able to prognosticate for OS when adjusted for other prognostic variables in the multivariable analysis (HR = 1.85, 95% CI = 1.27 to 2.71, P = .001; and HR = 4.51, 95% CI = 1.87 to 10.87, P = .001, respectively). The score classified patients into two groups with incremental risk of death: group A (0-2 points, 181 patients [63.9%], median OS = 19.4 months, 95% CI = 16.1 to 25.1) and group B (3-6 points, 102 patients [36.1%], median OS = 5.2 months, 95% CI = 3.6 to 6.9). 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.
Highlights
Neuroendocrine malignancies from the gastrointestinal (GI) tract are relatively rare, the incidence has been rising during recent years (1)
The score was prognostic for overall survival (OS) (HR 1.86, 95%CI 1.47-2.35; p
These results were validated in the external validation cohort (EVC) and prospective validation cohort (PVC); in which it was able to prognosticate for OS when adjusted for other prognostic variables in the multivariable analysis (HR 1.85 (95%CI 1.27-2.71), p-value 0.001 and HR 4.51 (95%CI 1.8710.87), p-value 0.001, respectively)
Summary
Neuroendocrine malignancies from the gastrointestinal (GI) tract are relatively rare, the incidence has been rising during recent years (1). Due to the impact on treatment strategy and survival, patients with neuroendocrine malignancies are classified according to both tumor morphology and assessment of proliferation according to WHO/ENETS guidelines. Gastrointestinal NECs (GI-NECs) represent only 5-10% of all digestive neuroendocrine malignancies (7, 8) and arise mainly from the stomach, pancreas, or colon (9-11). They are usually diagnosed in advanced stages, when only palliative treatment is available. In contrast to well-differentiated GI-NETs (1), the median survival of patients with NECs (all stages) is clinically significantly shorter (estimated to be around 12-17 months) due to their aggressive natural history (6, 12). 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)
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