Radiotherapeutics, clonal hematopoiesis, and risk of hematologic malignancies: The good, the bad, the ugly

While radiotherapeutics have demonstrated significant clinical benefit across multiple cancer types including thyroid cancer, neuroendocrine tumors, and prostate cancer, hematological toxicities can be frequent and challenging. It remains unknown to what extent the hematologic toxicity is driven by clonal processes that preexist and are selected for by treatment induced selection pressures. In this review, we discuss the background leading to the adoption of radiotherapeutics in the treatment of solid tumor malignancies, the risk of hematologic toxicities and myeloid neoplasms and the evidence pointing to potential precursor lesions that may predispose patients to hematologic toxicities. Additionally, we discuss how prevalent clonal hematopoiesis is among patients with solid tumor malignancies and suggest workflows for patients with cytopenias or clonal hematopoiesis who are receiving or have received radiotherapeutic agents.