Thymic health should be considered for radiotherapy planning

Radiation oncologists may need to consider the thymus when treating lung cancer, according to research published August 25 in Annals of Oncology.  

Researchers led by Hugo Aerts, PhD, from Mass General Brigham in Boston found that unintended radiation exposure to the thymus during lung cancer treatment is tied to worse clinical outcomes. They noted that this is relevant for patients who still have a relatively healthy, preserved thymus. 

“In these patients, higher radiation dose to the thymus was associated with a greater risk of distant cancer spread and poorer overall survival,” Aerts told AuntMinnie. 

Emerging evidence suggests that thymic health may influence oncological outcomes and all-cause mortality risk. However, the researchers noted that current radiotherapy practice does not consider the thymus as an organ of interest. Radiotherapy may expose the thymus to radiation. 

The Aerts team studied whether thymic radiation dose during lung cancer treatment is negatively linked to major clinical outcomes. 

The multicohort study included 1,107 patients with non-small cell lung cancer. Cohorts included the following: the phase III RTOG-0617 trial (n = 460); a real-world cohort of patients treated with chemoradiotherapy alone (Harvard-CRT; n = 422); and a real-world cohort of patients treated with a combination with consolidation immunotherapy (Harvard-Durva; n = 225). The researchers also used a deep learning system to quantify thymic function using radiographic characteristics. 

The team reported associations between incidental thymic irradiation and higher risk of distant metastases after confounding adjustments. It found that a 1-Gy increase in mean thymic dose was tied to an increased distant metastasis risk of 1.57% to 4.21%  

The team also performed a thymic health-stratified analysis. It reported that patients with preserved thymic health before radiotherapy “appeared to be at particularly greater risk,” while not observing any such associations in patients with impaired thymic health.  

One-year follow-up CT exams showed dose-dependent declines in thymic health and lower circulating lymphocyte counts, the researchers wrote. 

Aerts said the practical implication for radiation oncologists is considering the thymus during treatment planning. 

“Just as we routinely try to limit unnecessary radiation exposure to the heart, lungs, and other healthy organs, our findings suggest that in patients with a preserved thymus, we may also want to minimize thymic radiation when this can be done safely without compromising treatment of the tumor,” he told AuntMinnie. 

Aerts said clinicians should identify which patients have a preserved thymus, which could be found through routine CT scans. Treatment planning could then incorporate the thymus as an organ to avoid “when feasible.” 

“In our study, we performed radiation re-planning analyses and found that thymic exposure could often be reduced without compromising tumor coverage or substantially increasing radiation to other critical organs,” Aerts said. “This does not mean radiation oncologists should change practice immediately based on a retrospective study. The priority remains delivering the radiation needed to control the cancer. But our findings provide a strong rationale for prospective studies testing whether thymus-sparing radiation can preserve immune function and ultimately improve outcomes.” 

Aerts said the team is testing new radiation planning techniques and technologies that can further reduce thymic radiation dose exposure, including automated planning and proton therapy. 

“We are also studying how thymic health interacts with different cancer treatments, particularly immunotherapy, and whether it can help identify patients who are most likely to benefit from thymus-sparing approaches,” he said. 

Read the full study here.