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Purpose: Radiation therapy (RT) causes tissue damage and inflammation. Because cytokines play a key role in such processes, their expression levels can be an indicator of cell and tissue toxicity. This critical review aims to explore whether levels of circulating inflammatory biomarkers in peripheral blood are associated with proton- or photon-based therapy in the pelvic area and how these levels vary over time. Further, we investigated whether these levels can be linked to radiation dose, the incidence of toxicity, and changes in toxicity over time.

Methods and Materials: A literature search was conducted in PubMed to find studies involving comparative cohorts of pelvic irradiated patients with cancer. Studies reporting on the association of markers in peripheral blood with inflammatory processes and/or toxicity were included.

Results: We found evidence of associations between changes in inflammatory cytokine levels and the total cumulative dose-volume together with RT-induced toxicity in patients with cancer treated with pelvic RT. Common patient-reported outcomes demonstrate an association between radiation toxicity (eg, genitourinary toxicity) and circulating inflammatory biomarker levels.

Conclusions: This review highlights that the total cumulative dose and irradiated tissue volume are the primary drivers of RT-induced biomarker expression, influencing both early and late toxicity outcomes. The diversity in RT techniques, total dose, and number of treatment sessions across studies likely contributes to the variation in observed results. Circulating cytokine and biomarker levels in the blood can provide valuable monitoring and predictive insights for patients undergoing proton- or photon-based RT of the pelvis. Biomarker analysis in the context of RT offers clinical value by enabling personalized treatment by helping predict which patients are at higher risk for certain toxicities, guiding clinicians in tailoring treatment, optimizing supportive care, and adjusting RT plans. This approach could improve patient outcomes and quality of life by reducing long-term complications from radiation exposure.