3344 - A Phase I/II Dose-Escalation Study Evaluating the Safety of 21 Gy, 23 Gy, and 25 Gy for High Dose Rate (HDR) Prostate Brachytherapy: An Interim Report
Presenter(s)
D. Hong1, A. Willett1, M. J. Padgett2, K. Chen1, W. Liu1, J. Mikell1, M. B. Altman1, J. L. Garcia-Ramirez1, A. Guta1, E. Jeong2, P. D. H. Wall1, S. Edward2, J. E. Zoberi1, A. K. Bhatt1, M. Mahmood1, I. C. J. Hsu3, and H. A. Gay1; 1WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 2WashU Medicine, Department of Radiation Oncology, Saint Louis, MO, 3University of California San Francisco, Department of Radiation Oncology, San Francisco, CA
Purpose/Objective(s): Fractionated high–dose–rate (HDR) brachytherapy is an established treatment approach for low- to favorable intermediate-risk prostate cancer but is logistically complex. Single-fraction regimens may offer increased convenience and access to treatment, but 19-20.5 Gy have yielded suboptimal control. We aimed to determine whether dose-escalated single fraction HDR above 21Gy is safe and efficacious as this remains unknown.
Materials/Methods: We conducted a single-institution phase I/II dose-escalation trial of single-fraction HDR brachytherapy at 21 Gy, 23 Gy, and 25 Gy in patients with low- or favorable intermediate-risk prostate adenocarcinoma. The primary endpoint was biochemical recurrence–free survival (BRFS). Secondary endpoints included local control, patient-reported American Urological Association (AUA) scores, and acute and late common terminology criteria for adverse events (CTCAE) V5.0 toxicities. Longitudinal AUA scores were evaluated using a linear mixed-effects model with random patient intercepts by treatment arm. Biochemical and local disease-free survival metrics were estimated using Kaplan Meier models.
Results: Twenty-two patients were treated: nine received 21 Gy, eight received 23 Gy, and five received 25 Gy, with median (interquartile range) follow-up of 68 (67-71), 49 (45-55), and 12 (4-21) months, respectively. BRFS at 1 year was 100% across all arms; at 3 years, BRFS was 77.8% (95% CI, 54.9–100%) for 21 Gy and 90.0% (95% CI, 73.2–100%) for 23/25 Gy. The singular failure in the 23/25 Gy arm was under-staged, with seminal vesicle involvement at diagnosis and did not have any new areas of disease at time of biochemical failure and successfully salvaged. Local control is 100% to date across the dose-escalated cohort. (23/25 Gy) The time to nadir was statistically shorter for the 25 Gy (Median: 0.69 years, IQR: 0.63-0.98 years) group in relation to the 23 Gy (Median: 2.53 years, IQR: 1.87-3.60 years) and 21 Gy arms (Median: 1.41 years, IQR: 0.95-3.61, p<0.01). No grade 3 acute toxicities and no late grade =2 toxicities were observed. AUA scores decreased across arms over time ([-0.61] points per year, 95% CI: [-1.00] – [-0.22], p < 0.01).
Conclusion: At doses =23 Gy, local control within treatment field has been 100% to date, with statistically significant improvement in urinary symptoms, and no high-grade toxicities. Additional follow-up is necessary to establish the long-term efficacy of dose escalated regimens.