Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1,p≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2,p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide.
背景：鉴于胰腺神经内分泌肿瘤（pNEN）的罕见性和异质性，其治疗策略和顺序主要依据专家意见，循证依据有限。目的：探讨pNEN最常见药物治疗方案相关的总生存期（OS）、中位无进展生存期（mPFS）及预后因素。方法：回顾性单中心研究，纳入2000年至2020年间诊断并随访的患者（n=192）。结果：中位OS为36个月（95% CI：26-46），其中G1级为99个月，G2级为62个月，G3级为14个月，神经内分泌癌为10个月。接受生长抑素类似物（SSA）治疗的患者（n=59，中位Ki-67指数9%）mPFS为28个月。治疗线数（以一线治疗为参照，HR=4.1，95% CI：1.9-9.1，p≤0.001）成为疾病进展时间的独立危险因素。Ki-67指数≥10%的患者（n=28）mPFS为27个月。接受链脲佐菌素/5-氟尿嘧啶（STZ/5FU）治疗的患者（n=70，一线治疗n=68，中位Ki-67指数10%）mPFS为20个月，WHO分级是其独立危险因素（G1（n=8）对比G2（n=57），HR=2.8，95% CI：1.1-7.2，p=0.031）。肽受体放射性核素治疗（PRRT）（n=41，一线n=2，二线n=29，中位Ki-67指数8%）的中位PFS为21个月，卡铂联合依托泊苷（n=66，一线治疗n=60，中位Ki-67指数80%）为5个月，基于替莫唑胺的治疗（n=56，一线治疗n=17，中位Ki-67指数30%）为3个月。结论：（1）总生存期高度依赖肿瘤分级，符合预期；（2）SSA治疗的中位PFS约为2.5年，Ki-67指数高于或低于10%的肿瘤间无差异；（3）STZ/5FU作为一线治疗的mPFS达20个月，优于既往报道的靶向治疗数据；（4）PRRT在G2级pNEN中获得的mPFS与一线化疗相当；（5）卡铂联合依托泊苷或替莫唑胺治疗高级别肿瘤疗效有限。
肿瘤(癌症)患者之家