High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study

Abstract

Background High‐grade neuroendocrine carcinomas are rare in the gastrointestinal tract. However, treatment patterns and outcomes have not been well described. Subjects, Materials, and Methods The National Cancer Database was analyzed. The primary objective was to describe the clinical outcomes and identify prognostic factors. Univariate and multivariate analyses were done to identify factors associated with patient outcome. Results A total of 1,861 patients were identified between 2004 and 2013. The mean age was 63 years (standard deviation ±13). The majority of the patients (78.1%) were non‐Hispanic whites. The most common primary sites were pancreas (pancreatic neuroendocrine tumor [PNET] = 19.4%), large intestine (18.1%), esophagus (17.8%), and rectum (15.5%). Stage at presentation was I (6.6%), II (10.5%), III (18%) and IV (64.6%). Only 1.6% of the patients had brain metastases. Surgical resection was the primary therapy in 27.9%, and their median overall survival (OS) was 13.3 months. Patients treated with palliative chemotherapy had a median OS of 11.2 months, compared with 1.7 months for untreated patients. The median OS for high‐grade PNET was 6 months, compared with 9.9 months for other high‐grade gastrointestinal neuroendocrine carcinomas (HG GI NEC). On univariable analysis, age < 65 years (hazard ratio [HR] 0.72; 0.66–0.8; p < .001) and treatment at an academic center (HR 0.88; 0.79–0.99; p < .034) were associated with improved survival. Multivariable analysis confirmed prognostic advantage of treatment at an academic center. Conclusion This is the largest series of HG GI NEC. Most patients present with metastatic disease, and overall survival remains poor. Treatment at an academic center, younger age, and use of chemotherapy were associated with improved survival. Multiagent chemotherapy was found to be associated with superior survival compared with single‐agent chemotherapy, which was superior to no chemotherapy. Temporal sequences of chemotherapy, surgery, and radiation administration were not found to be associated with survival differences on multivariable analysis. Implications for Practice Management of patients with high‐grade gastrointestinal neuroendocrine carcinomas (HG GI NEC) is based on experience with small‐cell lung cancer. In this retrospective review, most patients had advanced disease and pancreatic primary had worse outcomes. Treatment at an academic center, younger age, and use of chemotherapy are associated with improved survival. Patients with early‐stage disease treated with resection alone had inferior outcomes compared with patients who received neoadjuvant or adjuvant therapy, suggesting that micrometastases contribute to poor surgical outcomes. The relatively high proportion of positive surgical margin favors downstaging with neoadjuvant therapy to improve resection and lower the risk of systemic recurrence.

Programmed cell death protein 1/programmed death ligand 1 but not HER2 is a potential therapeutic target in gastric neuroendocrine carcinoma

“…1,2 NECs are highly aggressive neoplasms that often present at an advanced stage; therefore, chemotherapy is often the primary therapeutic approach. 3 The prognosis of gastric NEC remains poor despite current treatment strategies, including platinum-containing regimens, which have been extrapolated from the management guidelines for small-cell lung cancer, [4][5][6] and there is an urgent need to identify molecular targets that are effective in patients with this aggressive neoplasm.…”

Chemotherapy in NEN: still has a role?

“…Thereafter, several small retrospective studies have reported ORRs for this regimen that widely range from 17 to 63% [70][71][72][73][74]. More recent large tumor registries have confirmed the efficacy of CDDP-VP-16 in this setting, although ORRs (28-48%) are generally lower than those reported for SCLC [69,[75][76][77][78].…”

Neoadjuvant on the gastroenteropancreatic neuroendocrine tumors: A Systematic Review and Meta-analysis

“…There has been a gradual growth in the incidence of NETs in recent years but no signi cant change in the survival of patients with high-grade NET [16,21]. This situation may re ect a lack of awareness in the treatment.…”

“…This situation may re ect a lack of awareness in the treatment. Given the biological similarities, the main treatment of NET was extrapolated from the experience in small-cell lung cancer (SCLC) currently [14,16,22]. Neoadjuvant therapy in SCLC has been proved effective in some studies [23][24][25].…”

“…According to the overall Newcastle-Ottawa Scale, the overall research quality was moderate (range, 5-8, mean 6.5, Table 2). Among the 8 studies, ve studies adopted adjuvant chemotherapy [13][14][15][16][17], one study chose PRRT [18], and two studies had PRRT combined with chemoradiotherapy [19,20]. In the studies involving chemotherapy, platinum-based regimens were the most common, with etoposide/cisplatin regimen accounting for the highest proportion.…”