Abstract：
High-grade neuroendocrine neoplasms (NENs) comprise both well-differentiated grade 3 neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) nearly always include poorly differentiated NEC as the neuroendocrine component. The efficacy and safety of frontline mFOLFIRINOX chemotherapy has never been investigated in patients with high-grade NENs.
We conducted a multi-institutional retrospective analysis of patients with advanced high-grade NEN of the gastroenteropancreatic tract or of unknown origin seen between February 2016 and April 2023 who received treatment with frontline mFOLFIRINOX.
A total of 35 patients were included (G3 NETs: n=2; NECs: n=25; MiNENs: n=8; stage III: n=5; stage IV: n=30). The objective response rate was 77% (complete response: 3%; partial response: 74%). Median progression-free survival was 12 months (95% CI, 9.2-16.2 months) and median overall survival was 20.6 months (95% CI, 17.2-30.6 months). No significant differences in efficacy were seen according to primary site, histopathology, and Ki-67 proliferative index. All 5 patients with stage III disease who received mFOLFIRINOX obtained an objective response and underwent radical surgery or definitive radiotherapy with curative intent, with a recurrence rate of 40%. Grade 3 or 4 adverse events were observed in 43% of patients (mainly neutropenia and diarrhea). Females were at significantly increased risk of developing severe toxicities.
mFOLFIRINOX shows antitumor activity against high-grade NENs. Well-designed, prospective clinical trials are needed to assess the efficacy of mFOLFIRINOX in both the neoadjuvant and metastatic settings.
We conducted a multi-institutional retrospective analysis of patients with advanced high-grade NEN of the gastroenteropancreatic tract or of unknown origin seen between February 2016 and April 2023 who received treatment with frontline mFOLFIRINOX.
A total of 35 patients were included (G3 NETs: n=2; NECs: n=25; MiNENs: n=8; stage III: n=5; stage IV: n=30). The objective response rate was 77% (complete response: 3%; partial response: 74%). Median progression-free survival was 12 months (95% CI, 9.2-16.2 months) and median overall survival was 20.6 months (95% CI, 17.2-30.6 months). No significant differences in efficacy were seen according to primary site, histopathology, and Ki-67 proliferative index. All 5 patients with stage III disease who received mFOLFIRINOX obtained an objective response and underwent radical surgery or definitive radiotherapy with curative intent, with a recurrence rate of 40%. Grade 3 or 4 adverse events were observed in 43% of patients (mainly neutropenia and diarrhea). Females were at significantly increased risk of developing severe toxicities.
mFOLFIRINOX shows antitumor activity against high-grade NENs. Well-designed, prospective clinical trials are needed to assess the efficacy of mFOLFIRINOX in both the neoadjuvant and metastatic settings.
摘要：
背景：高级别神经内分泌肿瘤(NENs)包括高分化3级神经内分泌肿瘤(G3NETs)和低分化神经内分泌癌(NECs)。混合性神经内分泌-非神经内分泌肿瘤(MINENs)几乎总是包括低分化的NEC作为神经内分泌成分。从未在高级别NENs患者中研究过一线mFOLFIRINOX化疗的疗效和安全性。
方法：我们对2016年2月至2023年4月期间接受一线mFOLFIRINOX治疗的胃肠胰道高级NEN患者或来源不明患者进行了多机构回顾性分析。
结果：共纳入35例患者（G3NETs：n=2；NECs：n=25；MiNENs：n=8；III期：n=5；IV期：n=30）。客观应答率为77%(完全应答:3%;部分应答:74%)。中位无进展生存期为12个月（95%CI，9.2-16.2个月），中位总生存期为20.6个月（95%CI，17.2-30.6个月）。根据原发部位，疗效无显著差异，组织病理学,和Ki-67增殖指数。所有5例接受mFOLFIRINOX治疗的III期患者均获得客观缓解，并接受根治性手术或根治性放疗，复发率为40%。在43％的患者中观察到3级或4级不良事件（主要是中性粒细胞减少和腹泻）。女性发生严重毒性的风险显着增加。
结论：mFOLFIRINOX对高级NENs具有抗肿瘤活性。精心设计,需要前瞻性临床试验来评估mFOLFIRINOX在新辅助治疗和转移治疗中的疗效.
方法：我们对2016年2月至2023年4月期间接受一线mFOLFIRINOX治疗的胃肠胰道高级NEN患者或来源不明患者进行了多机构回顾性分析。
结果：共纳入35例患者（G3NETs：n=2；NECs：n=25；MiNENs：n=8；III期：n=5；IV期：n=30）。客观应答率为77%(完全应答:3%;部分应答:74%)。中位无进展生存期为12个月（95%CI，9.2-16.2个月），中位总生存期为20.6个月（95%CI，17.2-30.6个月）。根据原发部位，疗效无显著差异，组织病理学,和Ki-67增殖指数。所有5例接受mFOLFIRINOX治疗的III期患者均获得客观缓解，并接受根治性手术或根治性放疗，复发率为40%。在43％的患者中观察到3级或4级不良事件（主要是中性粒细胞减少和腹泻）。女性发生严重毒性的风险显着增加。
结论：mFOLFIRINOX对高级NENs具有抗肿瘤活性。精心设计,需要前瞻性临床试验来评估mFOLFIRINOX在新辅助治疗和转移治疗中的疗效.
