D90 and D2CC Dose in Vaginal CTV as Dosimetric Predictors of Late Vaginal Side Effects in Postoperative Vaginal Modern Brachytherapy (Interventional Radiotherapy) After External Beam Irradiation in Endometrial Cancer.

Background/Objectives: To evaluate clinical and dosimetric predictors of vaginal toxicity in patients treated with vaginal-cuff brachytherapy (VCB), with or without external beam radiotherapy (EBRT), and assess the impact of different prescription and optimization strategies on dose-volume parameters. Methods: We retrospectively analyzed 217 patients treated with EBRT combined with VCB (n = 120) or VCB alone (n = 97). In VCB three prescription and optimization strategies (volume-based, graphical optimization, and 5 mm distance-based prescription) were compared to determine differences in dose-volume parameters. In patients who developed late vaginal side effects, the dosimetric parameters were evaluated using descriptive statistics and Cox regression modeling. Kaplan-Meier analysis was performed to assess time to toxicity. Results: In the EBRT+VCB cohort, 34/120 patients (28.3%) developed grade 1-2 vaginal toxicity compared to 35/97 (36%) in the VCB alone cohort. In the EBRT+VCB group, patients with toxicity received a higher D90 per fraction and higher vaginal D2cc. In multivariable analysis, vaginal D2cc (HR = 1.60, 95% CI = 1.01-2.54, p = 0.045) and CTV-DVH (HR = 0.77, 95% CI = 0.61-0.97, p = 0.027) were independently associated with toxicity. No significant dose-toxicity associations were observed in the VCB-alone cohort. Most events occurred within 48 months in both groups. Comparison of prescription strategies showed systematic differences in target and organ-at-risk dose-volume parameters, including vaginal D2cc. The 5 mm distance-based prescription consistently resulted in higher D90, D100, EQD2, and vaginal D2cc values. Conclusions: In patients receiving EBRT combined with VCB, both vaginal D2cc and target dose distribution were associated with vaginal toxicity. The prescription and optimization strategy significantly influenced dose-volume parameters. Planning methodology and dosimetric aspects should be considered when interpreting dose-toxicity relationships in vaginal brachytherapy.