Supplementary Material for: Chemotherapy in Resected Neuroendocrine Carcinomas of the Digestive Tract: A National Study from the French Group of Endocrine Tumours

Background: Neuroendocrine carcinomas (NECs) of the digestive tract are rare and aggressive tumours. In localised disease the treatment is surgery. Based on expert consensus, international guidelines recommend the administration of adjuvant chemotherapy combining etoposide and platinum derivatives, justified by the high risk of metastatic relapse. However, no clinical study has proven the benefit of neoadjuvant or adjuvant chemotherapy. Objectives: We aimed to evaluate the effect of neoadjuvant +/– adjuvant and adjuvant therapy in this indication. Methods: We performed a retrospective observational French study to evaluate overall survival (OS) and disease-free survival (DFS), prognostic factors for survival, and chemotherapy toxicity. Results: Seventy-three patients had surgical resection of a localised digestive NEC between January 1, 2000 and December 31, 2016. The majority of patients presented colorectal (35%) tumours and the median Ki-67 value was 70%. Forty-three patients received chemotherapy, either perioperative (neoadjuvant +/– adjuvant) or adjuvant. The median OS and DFS for the whole population was 24 and 9 months, respectively. The median OS and DFS for patients receiving chemotherapy was 62 and 13 months, respectively. Positive postoperative node status and Ki-67 ≥80% had a negative prognostic impact on OS and DFS. Administration of chemotherapy had a positive prognostic impact on OS and DFS. Sixteen grade 3/4 toxicities were reported without toxic death. Conclusions: Our results suggest a positive effect on survival of chemotherapy in resected digestive NECs, but further studies are needed to confirm these results.

背景：消化道神经内分泌癌（Neuroendocrine carcinomas, NECs）是一类罕见且侵袭性强的肿瘤。对于局限性病变，标准治疗方案为手术切除。基于专家共识，国际指南推荐采用依托泊苷（etoposide）联合铂类衍生物（platinum derivatives）的辅助化疗方案，该推荐依据为较高的转移性复发风险。但目前尚无临床研究证实新辅助化疗或辅助化疗的临床获益。
研究目的：本研究旨在评估新辅助±辅助治疗以及单纯辅助治疗在该适应证中的疗效。
研究方法：本研究为一项回顾性观察性法国队列研究，旨在评估总生存期（overall survival, OS）与无病生存期（disease-free survival, DFS）、生存预后因素以及化疗毒性反应。
研究结果：2000年1月1日至2016年12月31日期间，共73例局限性消化道神经内分泌癌患者接受了手术切除。其中多数患者为结直肠（colorectal）来源肿瘤（占比35%），中位Ki-67指数为70%。43例患者接受了化疗，包括围手术期（neoadjuvant +/– adjuvant）化疗或单纯辅助化疗。全人群的中位总生存期与无病生存期分别为24个月和9个月；接受化疗患者的中位总生存期与无病生存期分别为62个月和13个月。术后淋巴结阳性以及Ki-67指数≥80%对总生存期与无病生存期存在不良预后影响，而化疗的应用则对二者具有正向预后影响。本研究共报告16例3/4级毒性反应，未出现化疗相关死亡病例。
研究结论：本研究结果提示，化疗对接受手术切除的消化道神经内分泌癌患者的生存具有正向获益，但仍需开展进一步研究以验证该结论。