Total Body Irradiation and Smoking Interact to Increase Lung Cancer Risk after Blood or Marrow Transplantation

We evaluated the role of total body irradiation (TBI) and its interaction with smoking in increasing the risk of subsequent lung cancer after blood or marrow transplantation (BMT) leveraging the BMT Survivor Study. Participants included individuals who underwent BMT (1974-2014) at three centers and survived ≥2y. The impact of TBI and smoking was evaluated using Fine-Gray sub-distribution hazard models. Standardized incidence ratios were calculated using age- and sex-specific incidence rates obtained from the Surveillance, Epidemiology, and End Results Program. Of 6,981 BMT survivors (median age 46y, 58.5% male), 113 developed subsequent lung cancer at a median of 7y post-BMT, representing a 40% higher risk vs. the general population (95%CI=1.2-1.7). In the sub-cohort with smoking data (N=3,767), there was a significant TBI*smoking interaction (P<0.0001). Compared to no TBI never-smokers, the risk was increased among TBI-exposed ≥10y smokers (asHR=3.9; 95%CI=3.0-8.9), and no TBI ≥10y smokers (asHR=3.0; 95%CI=1.3-5.6). Among <10y smokers, the risk was not increased regardless of TBI-exposure (TBI: asHR=1.4; 95%CI=0.9-3.5; no TBI: asHR=1.1; 95%CI=0.3-4.3; reference: no TBI never-smokers). TBI-exposure in the absence of smoking did not increase subsequent lung cancer risk (asHR=0.6;95%CI=0.2-1.7). Additional risk factors include older age at BMT, male sex, and pre-BMT exposure to anthracyclines and/or topoisomerase II inhibitors. While BMT survivors who received TBI and smoked for ≥10y were at increased risk, TBI in the absence of cigarette smoking was not associated with increased risk. These findings support personalized surveillance for BMT survivors at heightened risk of subsequent lung cancer.