The impact of breast radiation technique on secondary lung cancer risk modeling: An analysis based on clinically delivered lung doses of various modern radiation techniques and target volumes.

Abstract

To estimate the projected lifetime risk of secondary lung cancer associated with breast radiotherapy based on actual clinically delivered lung doses for various modern radiation techniques and target volumes. Four cohorts consisting of Korean early-stage breast cancer patients were analyzed, treated with either stereotactic partial breast irradiation (S-PBI), 3D-conformal PBI (3D-PBI), VMAT whole breast irradiation (VMAT-WBI), or 3D-conformal WBI (3D-WBI). Using the clinically delivered mean lung dose (MLD) from CT-based dose planning, converted to biologically effective dose (EQD2, α/β = 3 Gy), we modeled the excess lifetime risk (ELR) and relative risk (RR) of secondary lung cancer using the RadRAT online calculator. Individual-level model uncertainty was propagated via bootstrap resampling. Age at exposure and treatment year were fixed at 50 years and 2026 (primary analysis); an as-treated analysis served as secondary. A total of 1,690 patients were included, among whom 3.8% (n = 68) were current or former smokers. Bootstrap-based median ELR of secondary lung cancer were 2,003, 1,931, 2,843, and 3,738 cases per 100,000 patients in the S-PBI, 3D-PBI, VMAT-WBI, and 3D-WBI cohorts, respectively. Both PBI groups had significantly lower ELR and RR than the two WBI groups (Bonferroni-corrected p < 0.05), whereas the two PBI groups did not differ significantly from each other; these findings remained consistent in the secondary as-treated analysis. The RR ranged from 1.54 to 2.05, raising the total lifetime risk from a baseline of 3.6% to 5.5-5.6% in the PBI groups and 6.4-7.3% in the WBI groups. Model-based projections suggest that adjuvant radiotherapy in early-stage breast cancer patients is associated with a dose-dependent increase in the risk of developing lung cancer during the remaining lifetime in Korean patients. A lower risk for secondary lung cancer is one of many factors to consider when deciding between PBI and WBI in low-risk breast cancer.