Gastrointestinal mixed adenoneuroendocrine carcinoma: a population level analysis of epidemiological trends

Abstract

Background: The rise in incidence and mortality of gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC) has not been well focused. The aim of our study was to examine epidemiological trends in incidence and incidence-based (IB) mortality of gastrointestinal MANEC at a population level.

Methods: The incidence and IB mortality of gastrointestinal MANEC as well as data on affected patients from 2000 to 2016 were obtained from the Surveillance, Epidemiology, and End Results database. Trends in incidence and IB mortality were assessed using Joinpoint regression. The Kaplan-Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression was used to identify independent predictors of mortality.

Results: 581 patients diagnosed with gastrointestinal MANEC were enrolled. Gastrointestinal MANEC incidence was 0.23 cases per 1,000,000 individuals in 2000 and 1.16 cases per 1,000,000 individuals in 2016, with an annual percent change (APC) of 8.0% (95% CI 5.7-10.3%, P < 0.05). IB mortality also showed a sustained increase (APC 12.9%, 95% CI 9.0-16.8%, P < 0.05). In Cox regression analysis, age at diagnosis, tumor grade and stage, lymph node metastasis, surgery, and tumor size were independently associated with mortality. Median survival was 75 months (95% CI 60-128 months). Median survival of appendiceal MANEC was significantly longer than that of cecal MANEC (115 vs. 31 months; P < 0.001).

Conclusions: We found a sustained and rapid increase both in incidence and IB mortality of gastrointestinal MANEC, manifesting that there has been no significant improvement in patient outcomes, nor progress in prevention and treatment. Additional resources should be devoted to gastrointestinal MANEC research.

Keywords: Annual percent change (APC); Epidemiology; Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC); Prognosis; Trend.

Fig. 1

Flow diagram of patient selection out of the total 783 patients in the SEER database 2000–2016

Fig. 2

Incidence and IB mortality trends in gastrointestinal MANEC, carcinoid and adenocarcinoma overall 2000–2016. a Incidence trends in gastrointestinal MANEC. b Incidence trends in gastrointestinal carcinoid. c Incidence trends in gastrointestinal adenocarcinoma. d IB mortality trends in gastrointestinal MANEC. e IB mortality trends in gastrointestinal carcinoid. f IB mortality trends in gastrointestinal adenocarcinoma. ^ mean that P < 0.05

Fig. 3

Incidence and IB mortality trends in appendiceal and cecal MANEC overall 2000–2016. a Incidence trends in appendiceal and cecal MANEC. b IB mortality trends in appendiceal and cecal MANEC

Fig. 4

Long-term survival outcomes using Kaplan–Meier’s analysis: a long-term survival outcomes in gastrointestinal MANEC, carcinoid and adenocarcinoma. The survival was better in gastrointestinal carcinoid (p < 0.001) and worsen in gastrointestinal adenocarcinoma (p = 0.0167) compared with gastrointestinal MANEC. b Long-term survival outcomes in localized, regional and distant gastrointestinal MANEC. Graph shows increasing survival from localized to distant (p < 0.001). The P values reported for survival analysis refers to comparison among all stage. c Long-term survival outcomes in treatment of gastrointestinal MANEC (p < 0.001). d Long-term survival outcomes in appendiceal and cecal MANEC (p < 0.001). e Long-term survival outcomes in gastrointestinal MANEC results of lymph node examination (p < 0.001). f Long-Term Survival Outcomes in tumor size of gastrointestinal MANEC (p < 0.001)