Published online Oct 28, 2018. doi: 10.3748/wjg.v24.i40.4586
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
Processing time: 119 Days and 3.1 Hours
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.
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.
To analyze true radiotherapy effect on developing an SPM in rectal cancer patients.
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.
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.
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.
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.