Radiotherapy in Patients with Autoimmune Diseases: Risks, Evidence, and Management Strategies

Abstract

Autoimmune diseases affect a substantial proportion of the global population, and affected individuals carry an elevated lifetime risk of developing various malignancies. When radiotherapy is indicated for cancer treatment in these patients, clinicians face the challenge of balancing oncological efficacy against the heightened risk of radiation-induced toxicity in tissues already compromised by chronic immune dysregulation. This review synthesizes the current evidence on the use of radiotherapy in patients with pre-existing autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis, inflammatory bowel disease, and multiple sclerosis. We examine the pathophysiological basis for increased radiosensitivity in autoimmune disease, encompassing impaired DNA repair mechanisms, aberrant cytokine signaling, compromised tissue homeostasis, and the confounding effects of immunosuppressive therapy. The evidence from retrospective cohort studies, case series, and institutional analyses is critically appraised, highlighting that connective tissue disorders, particularly systemic sclerosis and systemic lupus erythematosus, are associated with significantly elevated rates of severe acute and late toxicities, while other autoimmune conditions may confer more moderate risk. Management strategies are discussed in detail, including pre-treatment multidisciplinary assessment, individualized dose and fractionation modifications, advanced radiation delivery techniques to minimize normal tissue exposure, and coordinated immunosuppressive medication management. The role of emerging biomarkers for predicting individual radiosensitivity and the potential impact of modern radiation technologies such as intensity-modulated radiotherapy, stereotactic body radiotherapy, and proton therapy in mitigating toxicity are also reviewed. This article provides a comprehensive framework for evidence-based decision-making to optimize outcomes for autoimmune disease patients requiring radiotherapy in the Asia Pacific region and beyond.