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or females. Radiodynamic therapy (RDT) involves administration of a radiosensitizing agent and its subsequent activation by ionizing radiation for destruction of neoplastic cells. A comprehensive evaluation of the literature was performed to review the history of RDT using porphyrins for solid tumors, the cellular mechanisms of action, immunomodulatory effects, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). This manuscript was prepared in accordance with the PRISMA guidelines. A total of 271 articles