3293 - Phase I Dose-Escalation of Hypofractionated Pelvic Nodal Proton Radiotherapy with Simultaneous Integrated Prostate Boost
Presenter(s)
Y. Khamis1,2, K. Sun3, C. Eggleston3, A. N. Patel3,4, Z. H. Rana5, D. Kunaprayoon6, E. Straub3, Y. Kwok3, J. K. Molitoris3, S. M. Bentzen7, and M. V. Mishra3; 1University of Maryland, Department of Radiation Oncology, Baltimore, MD, 2Department of clinical oncology and nuclear medicine, Faculty of Medicine, Alexandria University, Alexandria, MD, 3Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 4Chesapeake Oncology Hematology Associates, Baltimore, MD, 5University of Maryland Medical Center, Baltimore, MD, 6University of Maryland, Department of Radiation Oncology, Baltimore, Maryland, USA, baltimore, MD, 7Department of Epidemiology and Public Health, Biostatistics and Bioinformatics Division, University of Maryland School of Medicine, Baltimore, MD
Purpose/Objective(s):
Hypofractionated radiotherapy may improve treatment efficiency while preserving oncologic outcomes in localized prostate cancer. Escalating the biologically effective dose (BED) to the prostate requires careful evaluation to limit gastrointestinal and genitourinary toxicity, particularly when pelvic nodal irradiation is included for node-positive disease. We hypothesized that progressively shortened hypofractionated proton therapy with a simultaneous integrated prostate boost (SIB) could safely escalate prostate BED while maintaining normal tissue BED constraints. Proton therapy was selected to further characterize pelvic dose deposition in the setting of hypofractionated nodal irradiation with SIB, where clinical data remain limited.Materials/Methods:
This single-institution phase I trial used a modified 3+3 dose-escalation design (2020 -2024). Patients with localized unfavorable intermediate- or high-risk prostate cancer received hypofractionated accelerated pelvic nodal proton radiotherapy with prostate SIB across three sequential dose levels (50 Gy/20 fractions, 58.4 Gy/16 fractions, and 52.2 Gy/12 fractions). Dose-limiting toxicity (DLT) was defined as any treatment-related CTCAE v5.0 grade =3 gastrointestinal, genitourinary, hematologic, or neurologic toxicity, or any grade 5 adverse event occurring during radiotherapy or within 90 days of treatment completion. Dose escalation proceeded if < 33% of patients experienced DLT. Toxicities were summarized descriptively by cohort. Median follow-up was estimated using the reverse Kaplan–Meier method. Biochemical progression free survival (bPFS) was calculated using Kaplan–Meier analysis from treatment initiation to biochemical failure, death, or last follow-up.Results:
Ten patients were treated across three dose levels (20 fractions, n=3; 16 fractions, n=3; 12 fractions, n=4), with a median age of 71 years; most had high-risk disease (9/10). No treatment-related DLT occurred. Acute and late adverse events were primarily grade 1–2 genitourinary symptoms, with no grade =3 treatment-related toxicities, and escalation proceeded through the final cohort. At a median follow-up of 30.7 months (95% CI, 20.9–39.1; range, 6.7-46), two events were observed (one biochemical recurrence and one non–prostate cancer death). Median bPFS was 46 months (95% CI, 28–64).Conclusion:
Hypofractionated accelerated pelvic nodal proton radiotherapy with a SIB prostate demonstrated favorable early safety across all evaluated dose levels. Delivery of 4.35 Gy per fraction over 12 fractions was feasible without dose-limiting toxicity. Longer follow-up is ongoing, and a phase II study is underway to further assess efficacy and late toxicity| Dose Level | RT Schedule | Total dose (Gy) | BED1.5 (Gy) Tumor | BED3 (Gy) Normal Tissue | |
| 1 | Nodal RT | 2.5 Gy x 20 | 50 | 133 | 93 |
| Prostate SIB | 3.15 Gy x 20 | 63 | 195 | 129 | |
| 2 | Nodal RT | 2.95 Gy x 16 | 47.2 | 140 | 93 |
| Prostate SIB | 3.65 Gy x 16 | 58.4 | 201 | 129 | |
| 3 | Nodal RT | 3.55 Gy x 12 | 42.6 | 143 | 93 |
| Prostate SIB | 4.35 Gy x 12 | 52.2 | 204 | 128 |