Multicohort analysis of impact of thymic radiation on outcomes of patients with non-small cell lung cancer

Emerging evidence indicates the functional importance of the thymus in adult health; yet current radiotherapy (RT) practice does not consider the thymus as an organ of interest. Because RT for non-small cell lung cancer (NSCLC) may incidentally expose the thymus to radiation, the thymic radiation dose may be negatively associated with clinical outcomes. A multicohort analysis included 1107 patients with NSCLC: the phase 3 RTOG-0617 trial (n=460), and two independent real-world cohorts of patients treated with chemoradiotherapy alone (HARVARD-CRT; n=422) or in combination with consolidation immunotherapy (HARVARD-DURVA; n=225). Mean thymic dose (MTD) was used to measure thymic radiation exposure. Incidental thymic irradiation was associated with increased risk of distant metastases after confounding adjustments. 1-Gy increase in MTD was associated with increased distant metastasis risk of 1.57% to 4.21% (RTOG-0617: aHR 1.29; p=0.0028; HARVARD-CRT: aHR 1.33; p=0.011; HARVARD-DURVA: aHR 1.95; p=0.007). In thymic health (TH)-stratified analyses, patients with preserved TH before RT appeared to be at particularly greater risk, whereas no associations emerged in patients with impaired TH. An exploratory feasibility study suggested that reoptimizing RT planning for thymic sparing can be achieved without compromising tumor coverage or cardiopulmonary constraints. The authors conclude that these findings raise awareness toward considering the thymus as an organ of interest in RT for NSCLC (graphical abstract).