This multicohort analysis of 1,107 NSCLC patients (RTOG-0617 phase III trial, n=460; HARVARD-CRT, n=422; HARVARD-DURVA, n=225) examined whether incidental thymic radiation dose — measured as Mean Thymic Dose (MTD) — is independently associated with distant metastasis risk, survival, and immune competence loss in patients treated with chemoradiotherapy, with or without consolidation immunotherapy.
Each 1 Gy increase in MTD was independently associated with a 1.57–4.21% higher risk of distant metastasis across all three cohorts (RTOG-0617: aHR=1.29, P=0.0028; HARVARD-CRT: aHR=1.33, P=0.011; HARVARD-DURVA: aHR=1.95, P=0.007); patients with preserved pre-RT thymic function were most at risk, while 1-year imaging showed dose-dependent declines in thymic health and lower circulating lymphocyte counts.
- Observational cohorts limit causal inference despite confounding adjustments. - Thymic function was estimated via a deep-learning radiographic proxy, not direct immunologic measurement. - The thymic-sparing RT replanning analysis was exploratory and feasibility-only, with no clinical outcome data yet.
Consider the thymus as an organ at risk during RT planning for NSCLC — especially in patients with intact thymic function — as even modest increases in mean thymic dose appear linked to higher metastasis risk. Thymus-sparing RT optimization appears feasible without sacrificing tumor coverage or cardiopulmonary constraints, and merits prospective evaluation.
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