Impact of Clonal Hematopoiesis on Solid Tumor Progression Following Radiation Therapy

Clonal hematopoiesis (CH) has been shown to adversely affect outcomes in patients with nonhematologic cancers. However, the effects of CH on response to specific treatments, including radiation therapy (RT), are unknown.

We analyzed patients with solid tumors harboring nonpathogenic somatic or germline ATM mutations (n = 144) and FAT1 mutations (n = 270) who received RT and underwent prospective tumor and matched WBC sequencing using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets assay. CH variants were detected in blood samples using a well-validated CH variant detection pipeline. We compared irradiated tumor progression in patients with and without CH. Nonpathogenic ATM mutations and FAT1 mutations have previously been shown not to be associated with response to RT.

The final cohort consisted of 412 patients who underwent 811 total courses of RT. One hundred sixty-one patients (39.1%) had CH; the most frequently mutated genes were DNMT3A (25.6%), PPM1D (6.2%), TET2 (5.8%), and TP53 (5.0%). Fine-Gray competing-risks analysis, with death treated as a competing event, showed no difference in irradiated tumor progression between patients with and without CH (hazard ratio, 1.09 [95% CI, 0.72 to 1.66]; P = .68). Similarly, subanalyses of CH variant allele frequency and CH mutations in putative cancer drivers did not reveal an association with RT response.

We found no difference in irradiated tumor progression between patients with and without CH. Further studies are warranted to examine the potential clinical implications of CH on treatment responsiveness of solid tumors.