Researchers at Mass General Brigham found that patients with non-small-cell lung cancer who receive a high incidental dose of radiotherapy to the thymus have an increased risk for metastasis and death, especially if they have preserved thymic function.
The thymus produces and educates T cells, and has traditionally been considered to have limited functional importance in adulthood.
However, recent work showed that many adults retain measurable thymic function throughout life, and that healthier thymuses are associated with lower mortality and improved responses to modern immunotherapies.
The researchers investigated the association between thymic radiation dose and clinical outcomes in patients with locally advanced NSCLC, using data from 1107 patients.
They found that a 1-Gy increase in mean thymic dose was associated with significant increased risks for distant metastases.
In an exploratory analysis, they showed that patients who received a mean thymic dose exceeding 35 Gy had a significant 40% greater risk for distant metastasis.
The association between thymic radiation dose and clinical outcomes was attenuated when the cohort was stratified by thymic health.
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Co-senior author Hugo Aerts noted that thymic health could become another piece of information available when treatment is being planned.
Aerts added that patients with preserved thymic health before treatment generally had the best outcomes overall, but within this group, higher radiation doses to the thymus were associated with a substantially greater risk for distant metastasis.
The researchers also showed that higher mean thymic dose was associated with an increased risk for metastases and death in patients with preserved thymic health but not in those with impaired thymic function.
The researchers are now planning to validate their findings in prospective studies to determine whether deliberately reducing radiation exposure to the thymus preserves thymic and immune function.
In practice, this development could mean that patients with NSCLC receive more personalized treatment plans, taking into account their individual thymic health, leading to better outcomes and improved quality of life.
The study’s findings have significant implications for the treatment of NSCLC, as prioritizing thymic health in radiation planning may reduce the risk of metastasis and improve patient outcomes.
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