Radiation biomarkers in body fluids: translational perspectives for precision radiotherapy-a narrative review

Radiotherapy and radionuclide therapy are essential components of modern cancer treatment. Despite substantial advances in radiation delivery and treatment planning, considerable interindividual variability remains in therapeutic response and radiation-induced toxicity. Conventional monitoring approaches, including imaging and routine laboratory tests, often provide limited insight into early or systemic biological responses. Body fluid-based biomarkers may provide accessible molecular readouts of radiation-induced damage, host response, and treatment-related toxicity. This narrative review summarizes radiation biomarkers detectable in body fluids, with emphasis on oxidative stress and cellular damage markers, circulating RNAs and extracellular vesicles, and metabolomic and lipidomic signatures relevant to precision radiation medicine.

A targeted literature search was conducted using PubMed/MEDLINE and Web of Science. Priority was given to primary experimental and clinical studies reporting specific molecular findings, longitudinal biomarker changes, or associations with treatment response and radiation-induced toxicity.

Ionizing radiation induces oxidative stress, DNA damage, inflammatory signaling, metabolic reprogramming, and intercellular communication, generating measurable signals in blood, plasma, serum, and urine. Oxidative DNA damage products such as 8-hydroxy-2'-deoxyguanosine and γ-H2AX-related responses may reflect cellular injury and toxicity risk. Circulating microRNAs and extracellular vesicle-associated cargo may capture transcriptional responses, bystander signaling, and treatment-related systemic changes. Metabolomic and lipidomic studies have identified multimetabolite signatures associated with radiation exposure and normal tissue toxicity. However, most candidate biomarkers remain exploratory, and clinical implementation is limited by variability in sampling, analytical platforms, normalization, and external validation.

Integrated longitudinal assessment of complementary biomarker classes, together with clinical and dosimetric information, may improve toxicity monitoring and treatment personalization. Prospective validation and methodological standardization are required before these biomarkers can support routine treatment adaptation.