Pulsed reduced dose rate radiotherapy: a narrative review.

Background and objective: Pulsed reduced dose rate (PRDR) radiotherapy, also known as pulsed low dose rate (PLDR) radiotherapy, involves delivering radiation at significantly lower dose rates in a pulsed manner (0.1-0.2 Gy/minute for a 3-minute interval resulting in a time-averaged, effective dose rate of 0.0667 Gy/min). This approach enhances tumor sensitivity while minimizing normal tissue damage, presenting a promising strategy for recurrent tumor treatment. This comprehensive review aims to consolidate the biological rationale, clinical applications, and prospects of PRDR radiotherapy across several disease sites.

Methods: We conducted a comprehensive literature search on the Medline database, ClinicalTrials.gov, and Google Scholar using various word combinations in the "title" field, including "PRDR", "Pulsed reduced dose rate", "Pulsed low dose rate", "PLDR" and various types of cancers. There were no limitations on the publication year. All obtained publications were reviewed, and their key references were cross-checked to ensure a balanced and high-quality review.

Key content and findings: PRDR has multiple radiobiologic advantages, including reoxygenation, redistribution, and immune regulation. These factors collectively contribute to PRDR's efficacy and reduced toxicity. PRDR has shown feasibility across multiple treatment modalities, including both intensity-modulated radiotherapy (IMRT) and pencil beam scanning (PBS) proton therapy, demonstrating significant potential in treating a variety of recurrent tumors. Clinical evidence supports its efficacy in central nervous system (CNS) tumors (i.e., glioma, meningioma, ependymoma, and brain metastases), recurrent breast cancer, head and neck cancers, gastrointestinal cancers, and cervical cancers.

Conclusions: PRDR radiotherapy shows promising efficacy and safety across various malignancies, especially in the re-irradiation setting. It is particularly effective for CNS tumors with manageable toxicity and shows potential in recurrent breast, head and neck, and gastrointestinal cancers. Treatment doses typically range from 40 to 66 Gy, depending on tumor type and clinical context. These findings position PRDR as a viable option for patients being considered for re-irradiation above traditional palliative doses. Large-scale clinical trials will likely further validate its efficacy and safety, along with studies aimed at understanding the underlying molecular mechanisms driving its unique therapeutic benefits. The role of PRDR is expected to expand, potentially offering new hope for patients with challenging cancer diagnoses.