Study Links Thymus Radiation Dose to Poorer Outcomes in Lung Cancer

The thymus is a small immune organ in the upper chest that supports T-cell development into adulthood. Historically it has been considered clinically irrelevant beyond puberty, so it is not routinely spared in radiotherapy planning. A new study shows that higher thymic radiation exposure is linked to worse outcomes in NSCLC, prompting evaluation of thymus-sparing strategies.

Researchers at Harvard University and Mass General Brigham used artificial intelligence (AI) to assess thymic health on routine computed tomography (CT) scans and to quantify radiation dose the organ received during treatment. The AI model generated a thymic health score from size, shape, density, and tissue composition. The analysis found that associations between thymic dose and outcomes were confined to patients with relatively well-preserved thymic tissue before therapy.

The study included 1,107 patients with NSCLC. It combined 460 participants from a randomized, prospective, phase III trial comparing 60 Gy versus 74 Gy carboplatin–paclitaxel chemoradiotherapy with or without cetuximab (RTOG-0617; November 2007 to June 2013) and 647 patients treated in routine practice. The latter comprised 422 who received platinum-based chemoradiotherapy between 2003 and 2014 (HARVARD cohort) and patients treated with chemoradiotherapy followed by durvalumab between 2017 and 2023 (HARVARD-durva cohort).

Across all three groups, higher radiation exposure to the thymus was associated with greater risk of distant metastasis, with relative increases of 29% in RTOG-0617, 33% in the Harvard chemoradiation cohort, and 95% in the cohort receiving chemoradiation followed by durvalumab. Patients with higher thymic doses also showed greater loss of thymic health one year later, and a smaller subgroup exhibited lower lymphocyte counts. The study also reported an increased risk of death in patients whose thymus was irradiated.

The findings, published in Annals of Oncology on August 25, 2026, suggest that thymus-sparing may be feasible using existing radiotherapy planning approaches without compromising tumor coverage or increasing heart or lung dose. The investigators emphasized that the thymus is not routinely considered an organ at risk in adults, highlighted the exploratory nature of a 35 Gy dose threshold used in analyses, and called for prospective validation. Limitations included potential treatment-selection bias and predominantly white patient populations.

“Perhaps most encouragingly, we found that protecting the thymus would not require a new treatment or new technology. Using existing radiotherapy planning techniques, radiation exposure to the thymus could often be substantially reduced without compromising treatment of the cancer or increasing radiation to other important organs. If future studies confirm that this improves outcomes, thymus-sparing could be implemented relatively rapidly in routine cancer care,” said Hugo Aerts, professor at Harvard University and director of the Artificial Intelligence in Medicine program at Mass General Brigham.

“Over the past several decades, radiation oncology has become increasingly successful at protecting healthy organs in the chest like the heart and lungs while maintaining excellent cancer control. Our findings suggest the thymus may deserve consideration alongside those organs. Importantly, this can often be achieved using existing treatment-planning techniques, meaning it could potentially be adopted relatively quickly if confirmed in prospective studies,” said Raymond Mak, radiation oncologist at Mass General Brigham and professor at Harvard Medical School.

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