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Updated: Feb 12, 2026
Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy
Published on: August 14, 2012
Sunitinib shrinks NET-G3 pancreatic neuroendocrine neoplasms
Yuki Mizuno1, Atsushi Kudo2, Takumi Akashi3
1Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
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.
Insights
Sunitinib shows similar effectiveness for well-differentiated pancreatic neuroendocrine tumors grade 3 (NET-G3) as for NET-G1/2. Poorly differentiated neuroendocrine carcinoma grade 3 (NEC-G3) showed worse progression-free survival with sunitinib treatment.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- The 2017 World Health Organization classification distinguishes pancreatic neuroendocrine neoplasms (Pan-NENs) into NET-G3 and NEC-G3.
- Treatment guidelines for these new classifications, particularly for drug selection, remain unclear.
Purpose of the Study:
- To evaluate the efficacy of sunitinib in patients with unresectable or metastatic Pan-NENs based on the 2017 classification.
- To determine tumor reduction rates, progression-free survival (PFS), and overall survival (OS) for NET-G3 and NEC-G3 treated with sunitinib.
Main Methods:
- A retrospective analysis of 60 patients with unresectable or metastatic Pan-NENs treated with sunitinib (37.5 mg).
- Tumor response was assessed using computed tomography and Response Evaluation Criteria in Solid Tumors (RECIST).
- Prognostic factors for PFS and OS were analyzed using Cox hazard models.
Main Results:
- Sunitinib achieved a median maximum tumor reduction of 18.3%, with partial response in 33.3% and stable disease in 48.3% of patients.
- Histologically poor differentiation (NEC-G3) was a significant negative prognostic factor for PFS (p=0.010).
- Patients with NET-G3 demonstrated significantly better PFS (p=0.005) and OS (p=0.012) compared to NEC-G3, with similar outcomes to NET-G1/2.
Conclusions:
- Sunitinib demonstrates comparable efficacy in well-differentiated pancreatic neuroendocrine tumor grade 3 (NET-G3) as in lower-grade tumors (NET-G1/2).
- Poorly differentiated pancreatic neuroendocrine carcinoma grade 3 (NEC-G3) is associated with poorer outcomes when treated with sunitinib.
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