Radiation to the thymus was found to be associated with worse outcomes in patients with non–small cell lung cancer (NSCLC), leading to an increased risk of metastasis, according to findings published in the Annals of Oncology.
“The thymus is currently not routinely treated as an important organ during radiation planning in adults. More broadly, our findings raise the possibility that preserving immune health during medical treatment may become a new principle of medicine. Modern oncology increasingly depends on the patient’s immune system, particularly as immunotherapies become part of standard treatment across many cancers. As we continue to improve cancer treatment, we may need to think not only about protecting organs such as the heart, lungs and spinal cord, but also about preserving the immune system itself. If confirmed in prospective studies, the thymus could become one of the first immune organs routinely protected during treatment planning,” said senior study author Hugo J. W. L. Aerts, PhD, Professor at Harvard University and Director of the Artificial Intelligence in Medicine (AIM) Program at Mass General Brigham.
Background and Study Methods
Emerging evidence, including two papers published in Nature by Dr. Aerts' team, has revealed the role of the thymus in adult health and how it can impact cancer outcomes.
“The thymus is a small immune organ located in the upper chest that helps produce and train T cells, which are essential for recognizing infections and fighting cancer. It is most active early in life and gradually shrinks with age when functional tissue is replaced by fat. For many years, people interpreted this as meaning the adult thymus was essentially irrelevant,” Dr. Aerts said.
His team conducted a multicohort analysis of patients with NSCLC (n = 1,107) who were treated with chemoradiotherapy or chemoradiotherapy plus consolidation immunotherapy. The participating patients came from the phase III RTOG-0617 trial and two independent real-world cohorts. Using deep learning, the researchers analyzed radiographic characteristics of the thymus in computed tomography (CT) scans as a marker for thymic function.
Mean thymic dose was used to measure the quantity of thymic radiation exposure.
Key Findings
The researchers found that incidental irradiation of the thymus was connected with a higher risk for distant metastasis, even after account for confounding factors.
A 1-Gy increase in the mean thymic dose was associated with higher risks of distant metastasis, ranging from 1.57% to 4.21%. In the RTOG-0617 cohort, the adjusted hazard ratio (aHR) was 1.29 (P = .0028), 1.33 in the real-world chemoradiotherapy cohort (P = .011), and 1.95 in the added immunotherapy real-world cohort (P = .007). “In all three patient groups, we found that higher radiation exposure to the thymus was consistently associated with a greater risk of the cancer spreading to distant parts of the body,” Dr. Aerts said.
Patients with preserved thymic health prior to radiation exposure had a greater risk compared with patients with impaired thymic health before radiation therapy.
One year after radiation, follow-up imaging showed dose-dependent declines in thymic health and lower circulating lymphocyte counts. The researchers thought that this could be due to a possible biological link between radiation to the thymus and loss of immune competence.
They then conducted an exploratory feasibility study, which suggested that reoptimizing radiation therapy planning to spare the thymus could be achieved without compromising tumor coverage or constraints around cardiopulmonary radiation.
“Perhaps most encouragingly, we found that protecting the thymus would not require a new treatment or new technology,” Dr. Aerts commented. “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.”
“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,” added co-senior study author Raymond H. Mak, MD, a radiation oncologist at Mass General Brigham Cancer Institute and a professor at Harvard Medical School.
DISCLOSURES: This work was supported by the National Institutes of Health National Cancer Institute, the European Union–European Research Council, the Deutsche Forschungsgemeinschaft, the Lundbeck Foundation, the Novo Nordisk Foundation, and a Savvaerksejer Jeppe Juhl og Hustru Ovita Juhl research stipend. For full disclosures of the study authors, visit annalsofoncology.org.
