R. Mulherkar1, D. Grimm2, P. Sukumvanich3, M. Courtney-Brooks4, M. M. Boisen3, J. L. Berger3, S. Taylor3, J. Lesnock3, S. Rush5, A. Garrett5, H. Mahdi6, J. T. Comerci7, A. Olawaiye5, E. Doraisamy2, M. Hajduk2, C. J. Houser8, H. Kim8, and J. A. A. Vargo IV1; 1UPMC Hillman Cancer Center, Department of Radiation Oncology, Pittsburgh, PA, 2UPMC Hillman Cancer Center, Pittsburgh, PA, 3UPMC Hillman Cancer Center, Department of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 4UPMC Magee Womens Hospital, Pittsburgh, PA, 5UPMC Hillman Cancer Center, Department of Gynecologic Oncology, Pittsburgh, PA, 6University of Pittsburgh, Department of Gynecologic Oncology, Pittsburgh, PA, 7Department of Gynecologic Oncology, Magee-Womens Hospital of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, 8Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA
Purpose/Objective(s): Although dose escalation in gynecologic brachytherapy improves local control, consensus guidelines recommend lower doses for template-based interstitial brachytherapy. Several factors, including tumor size and location, dose heterogeneity in interstitial implants, and twice daily fractionation cause inherent dose-escalation effects, potentially increasing toxicity. This study reports a single-institutional dose escalation experience in twice daily template-based interstitial brachytherapy treatments to demonstrate tumor control and toxicity outcomes, with the hypothesis that with image-based planning dose-escalation with interstitial brachytherapy is safe and meaningful. Materials/
Methods: Patients treated with template-based interstitial brachytherapy at our institution from 2006-2022 were identified. Local control and survival outcomes were analyzed using the Kaplan-Meier method and log-rank test to compare between groups. Formal tumor control probability (TCP) analysis was performed using logistic dose-response modeling. Grade 3+ toxicity (CTCAE version 5) was analyzed with time to event using Kaplan-Meier method and compared against total dose using log rank t-test between groups. Results: 214 patients were identified with median follow-up of 28.1 months (IQR 8.2-58.7). Total HDR dose correlated significantly with local and locoregional control when analyzed as a continuous variable, and when dichotomized around median dose of 25 Gy (p = 0.024). TCP analysis showed a dose-response effect between HR CTV D90 and local control in the entire cohort, and separately in cervical and vaginal cancer subsets. The actuarial 5-year incidence of grade 3 or worse toxicity was 6.1%, and there was no significant association between toxicity and total HDR dose or HR CTV D90. Conclusion: This study challenges recommendations that lower doses are required for interstitial brachytherapy. Local control correlated significantly with total HDR brachytherapy dose. TCP analysis showed dose-response relationship between HR CTV D90 and local control, with no significant correlation between toxicity and HDR brachytherapy dose or HR CTV D90. Dose-escalation with CT image-based planning aiming for HR CTV D90 of 80-85 Gy for cervical cancer and 75-80 Gy for vaginal cancer appears safe, and the higher doses in this range appear to improve local control.
