Redefining Chemotherapy-Related Headaches: From Pathobiology to Differential Diagnosis and Management

Chemotherapy-related headaches pose a significant challenge to the well-being and treatment adherence of cancer patients. Despite their prevalence, the underpinning mechanisms and pathobiology remain elusive, limiting treatment options. Herein, we review emerging causes, molecular and functional processes, and mechanisms at play, and discuss research and clinical gaps. We consider the iatrogenic and psychogenic effects of chemotherapy and highlight the need to distinguish chemotherapy-related headaches from primary headache disorders in cancer patients, including migraines or tension-type headaches. We discuss evolving biomarkers and mechanistic models that could facilitate the differential diagnosis and development of effective interventions. Given the global rise of cancer burden and better outcomes of chemotherapy with longer life expectancy, recognition of the detrimental impact of chemotherapy-related headaches and their integration into management plans are expected to improve treatment adherence and post-treatment life quality.