Department of Medical Oncology, European Neuroendocrine Tumor Society Centre of Excellence, The Christie NHS Foundation Trust, University of Manchester, Manchester M20 4BX, United Kingdom.
Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari 70121, Italy.
World J Gastroenterol. 2021 Mar 14;27(10):976-989. doi: 10.3748/wjg.v27.i10.976.
Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours (Wd-SBNETs), while and peptide receptor radionuclide therapy (PRRT) is frequently used as a second-line therapy. Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence.
To understand current practice and rationale for decision-making by physicians in the 3-line setting by building an online survey.
Weighted average (WA) of likelihood of usage between responders (1 very unlikely; 4 very likely) was used to reflect the relevance of factors explored.
Replies from representatives of 28 centers were received (5/8/2020-21/9/2020); medical oncologist (53.6%), gastroenterologist (17.9%); United Kingdom (21.4%), Spain (17.9%), Italy (14.3%). Majority from European Neuroendocrine Tumor Society (ENETS) Centres of Excellence (57.1%), who followed ENETS guidelines (82.1%). Generally speaking, 3-line treatment for Wd-SBNETs was: everolimus (EVE) (66.7%), PRRT (18.5%), liver embolization (LE) (7.4%) and interferon-alpha (IFN) (3.7%); chemotherapy (0%); decision was based on clinical trial data (59.3%), or personal experience (22.2%). EVE was most likely used if Ki-67 < 10% (WA 3.27/4) or age < 70 years (WA 3.23/4), in the 3-line setting (WA 3.23/4); regardless of presence/absence of carcinoid syndrome (CS), rate of progression or extent of disease. Chemotherapy was mainly utilised only if rapid progression (within 6 mo) (WA 3.35/4), Ki-67 10%-20% (WA 2.77/4), negative somatostatin receptor imaging (WA 2.65/4) or high tumour burden (WA 2.77/4); temozolomide or streptozocin was used with capecitabine or 5-fluorouracil (5-FU) (57.7%), FOLFOX (5-FU combined with oxaliplatin) (23.1%). LE was selected if presence of CS (WA 3.24/4) or Ki-67 < 10% (WA 2.8/4), after progression to other treatments (WA 2.8/4). IFN was rarely used (WA 1.3/4).
Everolimus was the most frequently used therapeutic option in the third-line setting. The most important factors for decision-making included Ki-67, rate of progression, functionality and tumour burden; since this decision is based on multiple factors, it highlights the need for a multidisciplinary assessment.
生长抑素类似物是分化良好的小肠神经内分泌肿瘤（Wd-SBNET）的既定一线治疗方法，而肽受体放射性核素疗法（PRRT）通常作为二线治疗方法。由于目前可用的最佳治疗序列的前瞻性数据有限，因此三线治疗的适当治疗选择仍然具有挑战性。
通过构建在线调查，了解医生在三线治疗环境中决策的当前实践和基本原理。
响应者（1 非常不可能；4 非常可能）之间使用使用概率的加权平均值（WA）来反映所探讨因素的相关性。
在 2020 年 5 月 5 日至 2020 年 9 月 21 日期间，收到了来自 28 个中心代表的回复；医学肿瘤学家（53.6%），胃肠病学家（17.9%）；英国（21.4%），西班牙（17.9%），意大利（14.3%）。大多数来自欧洲神经内分泌肿瘤学会（ENETS）卓越中心（57.1%），他们遵循 ENETS 指南（82.1%）。一般来说，Wd-SBNET 的三线治疗是：依维莫司（EVE）（66.7%），PRRT（18.5%），肝栓塞（LE）（7.4%）和干扰素-α（IFN）（3.7%）；化疗（0%）；决定基于临床试验数据（59.3%）或个人经验（22.2%）。在三线治疗中，Ki-67<10%（WA 3.27/4）或年龄<70 岁（WA 3.23/4）时，最有可能使用 EVE（WA 3.23/4）；无论是否存在类癌综合征（CS），进展速度或疾病程度如何。仅在快速进展（6 个月内）（WA 3.35/4），Ki-67 为 10%-20%（WA 2.77/4），生长抑素受体显像阴性（WA 2.65/4）或肿瘤负荷高（WA 2.77/4）时，主要使用化疗；替莫唑胺或链脲佐菌素联合卡培他滨或 5-氟尿嘧啶（5-FU）（57.7%），奥沙利铂联合 5-FU（FOLFOX）（23.1%）。在其他治疗进展后（WA 2.8/4），如果存在 CS（WA 3.24/4）或 Ki-67<10%（WA 2.8/4），则选择 LE。IFN 很少使用（WA 1.3/4）。
在三线治疗中，依维莫司是最常使用的治疗选择。决策的最重要因素包括 Ki-67、进展速度、功能和肿瘤负担；由于该决策基于多种因素，因此突出了需要进行多学科评估。
