Radiation to the Thymus Linked to Worse Outcomes in Lung Cancer Patients

Radiation reaching the thymus during treatment for non-small cell lung cancer (NSCLC) is associated with worse outcomes, according to a study of 1,107 patients published in the journal Annals of Oncology. The thymus, a small immune organ in the upper chest that helps produce and train T cells essential for fighting infection and cancer, was long thought to be of little use beyond puberty because it shrinks and is gradually replaced by fat with age.

The study's senior author, Hugo Aerts, a professor at Harvard University and director of the Artificial Intelligence in Medicine program at Mass General Brigham, said recent work by the same research team, published in two Nature papers, found that some adults retain substantially more functional thymic tissue than others, and that this remaining function is linked to greater T-cell diversity, better longevity, less cancer and improved outcomes after immunotherapy.

In the new study, researchers used artificial intelligence to analyze routine CT scans of 1,107 NSCLC patients from three groups — including 460 from the RTOG-0617 clinical trial and 647 treated in routine practice — to score the health of each patient's thymus before radiotherapy, then calculated how much radiation reached the organ during treatment. Among patients whose thymus was relatively healthy before treatment, higher thymic radiation doses were associated with a 29% higher risk of the cancer spreading to distant parts of the body in the RTOG-0617 trial, a 33% higher risk in one Harvard cohort, and a 95% higher risk in a cohort treated with chemoradiotherapy followed by the immunotherapy drug durvalumab.

Patients who received higher thymic radiation doses also showed a greater loss of thymic health a year later, and in a smaller subgroup tended to have lower lymphocyte counts, supporting the idea that radiation may directly damage the organ, Aerts said. Raymond Mak, a radiation oncologist at Mass General Brigham and co-senior author, said protecting the thymus could often be achieved using existing radiotherapy planning techniques, without compromising cancer treatment or raising radiation to other organs — though further studies are needed before doctors change how they plan treatment.