Second cancer risk after primary cancer treatment with three‐dimensional conformal, intensity‐modulated, or proton beam radiation therapy

Abstract

Background The comparative risks of a second cancer diagnosis are uncertain after primary cancer treatment with 3‐dimensional conformal radiotherapy (3DCRT), intensity‐modulated radiotherapy (IMRT), or proton beam radiotherapy (PBRT). Methods Pediatric and adult patients with a first cancer diagnosis between 2004 and 2015 who received 3DCRT, IMRT, or PBRT were identified in the National Cancer Database from 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system. The diagnosis of second cancer was modeled using multivariable logistic regression adjusting for age, follow‐up duration, radiotherapy (RT) dose, chemotherapy, sociodemographic variables, and other factors. Propensity score matching also was used to balance baseline characteristics. Results In total, 450,373 patients were identified (33.5% received 3DCRT, 65.2% received IMRT, and 1.3% received PBRT) with median follow‐up of 5.1 years after RT completion and a cumulative follow‐up period of 2.54 million person‐years. Overall, the incidence of second cancer diagnosis was 1.55 per 100 patient‐years. In a comparison between IMRT versus 3DCRT, there was no overall difference in the risk of second cancer (adjusted odds ratio [OR], 1.00; 95% CI, 0.97‐1.02; P = .75). By comparison, PBRT had an overall lower risk of second cancer versus IMRT (adjusted OR, 0.31; 95% CI, 0.26‐0.36; P < .0001). Results within each tumor type generally were consistent in the pooled analyses and also were maintained in propensity score‐matched analyses. Conclusions The risk of a second cancer diagnosis was similar after IMRT versus 3DCRT, whereas PBRT was associated with a lower risk of second cancer risk. Future work is warranted to determine the cost‐effectiveness of PBRT and to identify the population best suited for this treatment.

Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions

“…This difference allows for more precise targeting of protons to the malignancy and reduces potential damage to organs at risk, such as salivary glands. In a recent study comparing the development of secondary tumors following 3D-CRT, IMRT or PBRT, 3D-CRT and IMRT had similar rates of cancer recurrence, whereas PBRT showed reduced recurrence across cancer types [191]. Unfortunately, proton therapy is currently expensive and understudied, making it a less ideal option for most clinicians and patients [192].…”

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era

“…This requires a longer beam-on time and results in larger low dose volumes and more out-of-field ionizing dose to peripheral healthy tissue further away from the target (1,2). It is therefore increasingly recognized that modern RT might result in excess DNA damage in peripheral tissues, potentially increasing the risk of SPC, especially for young patients with favorable survival (3)(4)(5). To date, there are insufficient clinical data to draw firm conclusions about the impact modern RT has on SPC risks (6,7).…”

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study

“…Although VMAT signi cantly increased the dose delivered to the contralateral breast compared with that delivered by 3DCRT, the mean dose difference between these techniques was approximately 1 Gy. According to a recent study based on the National Cancer Database, which includes data regarding breast cancer and other tumor types, the relative risk of secondary cancer associated with IMRT is similar to that associated with 3DCRT [26], suggesting that these dose differences may not translate to clinically relevant outcomes in most middle-age and older women.…”