Risk of subsequent cancer diagnosis in patients treated with 3D conformal, intensity modulated, or proton beam radiation therapy.

Abstract

1503 Background: Approximately half of cancer patients receive radiation therapy (RT). Modern RT modalities (3D conformal [3DCRT], intensity modulated [IMRT], proton beam [PBRT]) have been theorized to pose different risks of second cancers, but the relationship between RT modality and subsequent cancers has been unclear due to their rarity. Methods: Pediatric and adult patients with a first cancer diagnosis who received 3DCRT, IMRT, or PBRT were identified in the National Cancer Database. To analyze a more uniform population, cases were required to be non-metastatic and have at least 2 years of follow-up time. Ten cancer types were included: head/neck, upper gastrointestinal (GI), lower GI, gynecological, lymphoma, non-small cell lung, prostate, breast, bone/soft tissue, and brain/central nervous system. Diagnosis of a subsequent cancer was determined using a variable denoting the sequence of malignant neoplasms over the lifetime of the patient. The risk of subsequent cancer diagnosis was modeled using multivariable logistic regression adjusting for age, follow-up time, cancer type, RT dose, chemotherapy, and other factors. Propensity score matching was additionally used to balance baseline characteristics. Results: In total, 430,866 patients were included (33.4% 3DCRT, 65.1% IMRT, 1.5% PBRT) with median follow-up of 5.0 years and total follow-up period of 2.35 million person-years. In the comparison of IMRT relative to 3DCRT, there was no difference in the risk of subsequent cancer diagnosis (adjusted odds ratio [OR] 1.01; 95% confidence interval [CI] 0.98-1.03; p = 0.62). In contrast, recipients of PBRT had significantly lower risk of subsequent cancer diagnosis relative to IMRT (adjusted OR 0.31; 95% CI 0.26-0.37; p < 0.0001). The benefit associated with PBRT persisted in sensitivity analyses that excluded patients with prostate cancer (71.6% of the PBRT cases), receipt of chemotherapy, and/or follow-up time less than 5 years. Conclusions: Risk of subsequent cancer diagnosis was similar between IMRT and 3DCRT and significantly lower for PBRT. PBRT may be preferred in situations where avoidance of second cancers is paramount, such as pediatrics and young adults.