Patient-related risk factors for late toxicity after pelvic cancer radiotherapy

This thesis, Patient-Related Risk Factors for Late Toxicity after Pelvic Cancer Radiotherapy, investigates clinical and genetic determinants of late adverse effects following external beam radiotherapy for pelvic cancer, with a focus on prostate and cervical cancer. Despite technical advances that have reduced exposure to organs at risk such as the bladder and bowel, radiation-induced complications remain a substantial burden, especially as cancer survivorship increases.
A literature review identified smoking, prior surgery, and severe acute toxicity as consistent clinical risk factors, while genetic predisposition emerged as an important yet complex contributor. To assess normal tissue radiosensitivity, we used the γ-H2AX assay to generate a functional marker of DNA repair capacity. Impaired DNA repair, quantified by the γ-H2AX foci decay ratio, was the strongest predictor of late toxicity in prostate cancer, though validation in a broader pelvic cancer cohort was limited by low event rates due to modern treatment techniques.
Patient-reported outcomes were also assessed, revealing that patients generally reported greater symptom severity than clinicians, underscoring the value of integrating both perspectives for comprehensive toxicity assessment.
The findings suggest that as radiotherapy techniques continue to improve, variability in individual radiosensitivity becomes the key driver of late toxicity. Personalized treatment strategies that incorporate both genetic and clinical risk factors hold promise for reducing treatment-related harm. Future clinical trials should explore genetically guided radiotherapy, while actionable factors such as smoking must be routinely addressed in clinical practice.