Clonal Hematopoiesis of Indeterminate Potential After Radiation Therapy

PURPOSE: Clonal hematopoiesis of indeterminate potential (CHIP) is a condition associated with increased risk of hematologic malignancies and cardiovascular diseases. Although radiation therapy has been identified as a risk factor for CHIP, specific radiation factors that influence the development of CHIP remain unclear. METHODS AND MATERIALS: We identified 489 patients with cancer who underwent radiation therapy (RT) at least 6 months prior to blood samples being deposited in an institutional biorepository. Patients with prior hematologic malignancy diagnosis or cytotoxic chemotherapy exposure were excluded. Targeted DNA sequencing of the blood samples was performed to detect mutations in CHIP-associated genes. CHIP prevalence was compared with a control cohort of 854 cancer patients without exposure to RT or chemotherapy. RT parameters, including dose, technique, and irradiated site, were characterized and examined for association with CHIP prevalence. RESULTS: CHIP was detected in 23% of patients who received RT. The probability of CHIP was increased in patients who received RT compared with the patients who did not (odds ratio, 1.49; 95% confidence interval, 1.08-2.05), after adjusting for age, sex, race, smoking status, and metastatic disease status. The risk of CHIP positively correlated with the biologically equivalent dose (Pearson correlation coefficient, r = 0.64, P < .001). CHIP was associated with the stereotactic technique (OR, 2.56; 95% CI, 1.01-6.34) and was more prevalent in patients with primary lung cancer and patients who received radiation to the spine. We observed 5 cases of subsequent myelodysplastic syndrome and 1 case of subsequent acute myeloid leukemia in the RT cohort with a median interval of 6.3 years between RT and diagnosis, and 1 case of myelodysplastic syndrome in the control cohort, 7.5 years after blood sample collection. CONCLUSIONS: In this cohort study, prior RT was associated with an increased risk of clonal hematopoiesis, particularly among patients receiving higher biologically equivalent radiation doses, stereotactic techniques, or treatment to the spine.