Hypofractionated radiotherapy across cancer sites: a narrative review of evidence and implementation

Hypofractionated radiotherapy (HFRT), which delivers higher doses per fraction in fewer treatment sessions, represents a practical form of de-escalation in radiation by shortening overall treatment time and reducing patient burden. This narrative review summarizes the current evidence for HFRT across various malignancies. For breast cancer, randomized trials including the START trials and JCOG 0906 have established moderate HFRT (40-42.56 Gy in 15-16 fractions) as standard care after breast-conserving surgery. In localized prostate cancer, multiple trials have demonstrated equivalent biochemical control with moderate HFRT compared to conventional fractionation. For early-stage glottic cancer, HFRT achieves comparable or superior local control with acceptable toxicity. In elderly glioblastoma patients, HFRT with concurrent temozolomide has become a standard treatment option. For vulnerable patients unable to tolerate standard chemoradiotherapy, HFRT provides a valuable alternative, although caution is required when combining with chemotherapy. In palliative settings, single-fraction radiotherapy is established for painful bone metastases, while split-course regimens such as QUAD shot offer effective palliation for bulky tumors. Despite robust evidence, HFRT adoption varies across regions, with barriers including reimbursement structures and institutional capacity. HFRT reduces healthcare costs while maintaining outcomes, making it an attractive option in resource-limited settings. Continued efforts are needed to promote evidence-based HFRT implementation worldwide.