Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2018; 24(40): 4586-4595
Published online Oct 28, 2018. doi: 10.3748/wjg.v24.i40.4586
Second primary malignancy risk after radiotherapy in rectal cancer survivors
Ti-Hao Wang, Chia-Jen Liu, Tze-Fan Chao, Tzeng-Ji Chen, Yu-Wen Hu
Ti-Hao Wang, Department of Radiation Oncology, China Medical University Hospital, Taichung 40447, Taiwan
Chia-Jen Liu, Department of Medicine, Taipei Veterans General Hospital, Division of Hematology and Oncology, Taipei 11217, Taiwan
Tze-Fan Chao, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
Tzeng-Ji Chen, Department of Family Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
Yu-Wen Hu, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
Yu-Wen Hu, Institute of Public Health, National Yang-Ming University, Taipei 11217, Taiwan
Author contributions: Wang TH, Liu CJ, Chao TF, Chen TJ and Hu YW designed research; Wang TH, Liu CJ and Chao TF performed research; Wang TH, Chen TJ and Hu YW contributed new reagents or analytic tools; Wang TH and Hu YW analyzed data; Wang TH wrote the paper.
Institutional review board statement: This study was exempted from full review by the Institutional Review Board (No. 2016-05-007BC).
Conflict-of-interest statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Yu-Wen Hu, MD, Attending Doctor, Department of Oncology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road, Beitou District, Taipei 11217, Taiwan. ywhu@vghtpe.gov.tw
Telephone: +886-2-28757270 Fax: +886-2-28732131
Received: June 30, 2018
Peer-review started: July 2, 2018
First decision: July 18, 2018
Revised: August 14, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: October 28, 2018
ARTICLE HIGHLIGHTS
Research background

Previous literature on second primary malignancy (SPM) risk after radiotherapy in rectal cancer survivors yielded controversial results. Also, lack of comorbidities, chemotherapy, and competing risk adjustment may cause biased conclusion. In addition, whether different radiotherapy regimens results in different SPM risk has not been investigated. In this study, we meticulously collected and analyzed all factors may contribute in SPM, and yielded true radiotherapy effect.

Research motivation

The risk of developing an SPM has received greater attention in clinical practice. Although several studies have investigated the relationship between radiotherapy and SPM in rectal cancer patients, the conclusions have been diverse.

Research objectives

To analyze true radiotherapy effect on developing an SPM in rectal cancer patients.

Research methods

We used Taiwan’s National Health Insurance Research Database to identify rectal cancer patients between 1996 and 2011. The cohort was composed of patients aged 20 years or older who were diagnosed with a first primary rectal cancer. SPM risk was analyzed by competing risk model. The overall and site-specific SPM incidence rates were compared among the radiotherapy groups by multivariate Cox regression, taking chemotherapy and comorbidities into account. Sensitivity tests were performed for attained-year adjustment and long-term survivor analysis.

Research results

In this large-scale population-based cohort study, we found no increase of SPM due to radiotherapy in rectal patients. Different radiotherapy regimens results in same SPM risk. Factors that were significantly associated with a higher risk for SPMs included male sex, age, liver cirrhosis, autoimmune disease, and COPD. Compared with the surgery-only group, a significantly increased HR for SPM in the radiotherapy group was only evident for lung cancer (HR = 1.42, 95%CI: 1.04-1.93; P < 0.001). The risk of bladder, uterus, skin, and hematologic cancer was elevated in irradiated patients, but the difference was not statistically significant.

Research conclusions

This study confirmed no increased risk of SPM due to radiotherapy in rectal patients. Many secondary malignancy may only reflect the patients’ genetic backgrounds, cancer-related treatments, lifestyles, and environmental risk factors. After careful confounder adjustment and appropriate statistical analysis, no radiotherapy effect on SPM can be drawn. This is an important conclusion to both patients and physicians.

Research perspectives

Some comorbidities confounders have profound effects on developing secondary malignancy. Also, death is a strong competing risk need to handle. In future, we need to explore and investigate the mechanism of oncogenic effect of radiotherapy, especially in cancer outside radiation volume.