Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Department of Human Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
J Cancer Res Clin Oncol. 2018 Jun;144(6):1155-1163. doi: 10.1007/s00432-018-2636-2. Epub 2018 Mar 30.
The 2017 revised World Health Organization classification of pancreatic neuroendocrine neoplasms classified conventional G3 tumors into well-differentiated (NET-G3) and poorly differentiated (NEC-G3) tumors. However, guidelines for selection of drug therapy were not established in the 2017 revision. This study aimed to elucidate the rates of maximum tumor reduction of sunitinib, progression-free survival, and overall survival in the new classification.
We investigated the reduction rate over time using computed tomography for 60 patients with unresectable or distant metastatic pancreatic neuroendocrine neoplasms who received 37.5 mg of sunitinib in our department from April 2013 to November 2017.
Of the 60 cases, 42, 10, and 5 were NET-G1/G2, NET-G3, and NEC-G3, respectively. The prognostic factors were analyzed according to clinicopathological factors using the Cox hazard model. The median observation period was 19 months, and the median duration of sunitinib administration was 7 months. The median maximum reduction rate of sunitinib was 18.3%. Tumor response was classified according to the Response Evaluation Criteria in Solid Tumors: 20 cases (33.3%) showed partial response, 29 cases (48.3%) showed stable disease, and 11 cases (18.3%) showed progressive disease. In a multivariate analysis of factors contributing to progression-free survival from the start of sunitinib administration, only histologically poor differentiation was a significant factor (p = 0.010). Progression-free survival and overall survival were significantly better in patients with NET-G3 than that in patients with NEC-G3 (p = 0.005, p = 0.012), while it was not different between those with NET-G3 and those with NET-G1/2.
Our results indicate that sunitinib is as effective for NET-G3 as for NET-G1/2.
2017 年世界卫生组织修订的胰腺神经内分泌肿瘤分类将传统的 G3 肿瘤分为分化良好型(NET-G3)和分化差型(NEC-G3)肿瘤。然而,2017 年修订版并未制定药物治疗选择的指南。本研究旨在阐明新分类中舒尼替尼的最大肿瘤缓解率、无进展生存期和总生存期。
我们调查了 2013 年 4 月至 2017 年 11 月在我科接受 37.5mg 舒尼替尼治疗的 60 例不可切除或远处转移性胰腺神经内分泌肿瘤患者的 CT 随时间的肿瘤缩小率。
60 例患者中,NET-G1/G2、NET-G3 和 NEC-G3 分别为 42、10 和 5 例。采用 Cox 风险模型根据临床病理因素对预后因素进行分析。中位观察期为 19 个月,舒尼替尼中位治疗时间为 7 个月。舒尼替尼的中位最大缓解率为 18.3%。根据实体瘤反应评价标准(Response Evaluation Criteria in Solid Tumors)对肿瘤反应进行分类:20 例(33.3%)为部分缓解,29 例(48.3%)为稳定疾病,11 例(18.3%)为进展性疾病。在开始舒尼替尼治疗时无进展生存期的多因素分析中,只有组织学分化差是一个显著的因素(p=0.010)。NET-G3 患者的无进展生存期和总生存期明显优于 NEC-G3 患者(p=0.005,p=0.012),而 NET-G3 患者与 NET-G1/2 患者之间则无差异。
我们的结果表明,舒尼替尼对 NET-G3 的疗效与 NET-G1/2 相同。