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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Active surveillance in metastatic pancreatic neuroendocrine tumors: A 20-year single-institutional experience
He-Li Gao, Wen-Quan Wang, Hua-Xiang Xu, Chun-Tao Wu, Hao Li, Quan-Xing Ni, Xian-Jun Yu, Liang Liu
He-Li Gao, Wen-Quan Wang, Hua-Xiang Xu, Chun-Tao Wu, Hao Li, Quan-Xing Ni, Xian-Jun Yu, Liang Liu, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
He-Li Gao, Wen-Quan Wang, Hua-Xiang Xu, Chun-Tao Wu, Hao Li, Quan-Xing Ni, Xian-Jun Yu, Liang Liu, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
He-Li Gao, Wen-Quan Wang, Hua-Xiang Xu, Chun-Tao Wu, Hao Li, Quan-Xing Ni, Xian-Jun Yu, Liang Liu, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
He-Li Gao, Wen-Quan Wang, Hua-Xiang Xu, Chun-Tao Wu, Hao Li, Quan-Xing Ni, Xian-Jun Yu, Liang Liu, Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
Author contributions: Gao HL, and Wang WQ contributed equally to this work, in conducting clinical observations, analyzing the data, and writing the manuscript; Xu HX, Li H, Wu CT, Zhang WH, and Ni QX performed the research; Yu XJ, and Liu L contributed equally to this work, in designing the research, revising the manuscript, and providing valuable suggestions for this study.
Supported by the National Natural Science Foundation of China, No. 81802675, No. 81871941, No. 81872366, No. 81827807, and No. 81702341; the National Science Foundation for Distinguished Young Scholars of China, No. 8162500008; the Outstanding Academic Leader Program of the Technological Innovation Action Plan in Shanghai Science and Technology Commission, China, No. 18XD1401200; and the Young Talented Specialist Training Program of Shanghai, China, No. 19ZR1410800.
Institutional review board statement: This study was reviewed and approved by the Human Research Ethics Committee of Fudan University Shanghai Cancer Center.
Informed consent statement: Written informed consent was acquired from each patient.
Conflict-of-interest statement: The authors have no financial disclosures or conflicts of interest related to this submission.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Liang Liu, MD, PhD, Professor, Surgeon, Surgical Oncologist, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong An Road, Shanghai 200032, China.
liuliang@fudanpci.org
Received: February 29, 2020
Peer-review started: February 29, 2020
First decision: April 2, 2020
Revised: May 9, 2020
Accepted: August 9, 2020
Article in press: August 9, 2020
Published online: September 6, 2020
Processing time: 188 Days and 1.4 Hours
BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous and indolent; systemic therapy is not essential for every patient with metastatic PanNET. The National Comprehensive Cancer Network guidelines state that delaying treatment is an option for PanNET with distant metastasis, if the patient has stable disease. However, specific factors that influence surveillance were not mentioned. In addition, data regarding the period of active surveillance in patients with metastatic PanNET are lacking.
AIM
To specifically determine factors influencing active surveillance in patients with liver metastatic nonfunctioning PanNETs (NF-PanNETs).
METHODS
Seventy-six patients with liver metastatic NF-PanNETs who received active surveillance from a high-volume institution were enrolled. Time to disease progression (TTP) and time to initiation of systemic therapy were determined.
RESULTS
Thirty-one (40.8%) patients had recurrent liver disease after R0 resection; 45 (59.2%) were diagnosed with liver metastasis. The median follow-up period was 42 mo and 90.7% patients were observed to have disease progression. The median TTP (mTTP) was 10 mo. Multivariate analysis showed that the largest axis of the liver metastasis > 5 mm (P = 0.04), non-resection of the primary tumor (P = 0.024), and T3-4 stage (P = 0.028) were associated with a shorter TTP. The mTTP in patients with no risk factors was 24 mo, which was significantly longer than that in patients with one (10 mo) or more (6 mo) risk factors (P < 0.001). A nomogram with three risk factors showed reasonable calibration, with a C-index of 0.603 (95% confidence interval: 0.47-0.74).
CONCLUSION
Active surveillance may only be safe for metastatic NF-PanNET patients with favorable risk factors, and other patients progressed rapidly without treatment. Further studies with a larger sample size and a control group are needed.
Core tip: Experience in active surveillance of metastatic pancreatic neuroendocrine tumors (PanNETs) is insufficient in clinical practice. This study includes the experience of active surveillance in 76 patients with liver metastatic nonfunctioning PanNETs (NF-PanNETs) over 20 years. We demonstrated that largest axis of the liver metastasis > 5 mm, non-resection of the primary tumor and T3-4 stage are poor prognostic factors and affect the survival of PanNET patients with liver metastasis. Patients with favorable factors had a time to progressive disease of more than two years without systemic treatment. This subset of PanNET patients with liver metastasis should undergo active surveillance.
