Yuki Mizuno1, Atsushi Kudo2, Takumi Akashi3, Keiichi Akahoshi1, Toshiro Ogura1, Kosuke Ogawa1, Hiroaki Ono1, Yusuke Mitsunori1, Daisuke Ban1, Shinji Tanaka4, Ukihide Tateishi5, Minoru Tanabe1. 1. 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. 2. 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. kudomsrg@tmd.ac.jp. 3. Department of Human Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 4. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 5. Department of Diagnostic Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our results indicate that sunitinib is as effective for NET-G3 as for NET-G1/2.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our results indicate that sunitinib is as effective for NET-G3 as for NET-G1/2.
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