3258 - Stereotactic Magnetic Resonance-Guided Adaptive Radiation Therapy (SMART) for Pelvic Reirradiation: A Phase 1/2 Trial
Presenter(s)
A. Droznin1, P. J. Catalano2, S. Chirmade3, M. Kinz4, G. Benham3, B. Zhai5, P. L. Nguyen6, M. T. King4, A. V. DAmico7, N. E. Martin3, Z. Han4, J. Kukluk8, K. Singhrao4, R. van Dams9, R. H. Mak10, and J. E. Leeman7; 1Brigham and Women's Hospital/ Dana Farber Cancer Institute, Boston, MA, 2Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, 3Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 4Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 5Brigham & Women's Hospital, Boston, MA, 6Mass General Brigham Cancer Institute, Boston, MA, 7Department of Radiation Oncology, Mass General Brigham, Harvard Medical School, Boston, MA, 8Brigham and Women's Hospital, Boston, MA, 9Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, 10Department of Radiation Oncology, Mass General Brigham/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Purpose/Objective(s):
Conventional external beam reirradiation (reRT) of the pelvis is associated with significant risk of urinary and rectal complications. We hypothesized that stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) minimizes risk of toxicity by allowing for improved precision of treatment delivery to previously irradiated pelvic tumors.
Materials/Methods:
This prospective phase 1/2 clinical trial was a sub-protocol of a prospective master protocol evaluating SMART with a 0.35T MR-Linac for multiple oncologic indications. Enrolled patients had biopsy-proven or strong clinical/radiographic evidence of pelvic recurrence within a previous radiation field. The primary endpoints for the phase 1 were feasibility and safety of SMART reRT of pelvic tumors and for the phase 2 was CTCAE v5.0 grade 3+ toxicity. Secondary endpoints included rates of disease control, overall survival, patient-reported outcome measures (PROMs), dosimetry metrics, and MR-Linac gating duty cycle.
Results:
Thirty patients with prostate adenocarcinoma were enrolled and treated between 1/2022 and 6/2024 (n=10 phase 1, n=20 phase 2). Six were treated to the prostate, 16 were treated to the prostate/seminal vesicle bed and 8 were treated to pelvic lymph nodes. The median prior RT dose was 68.4 Gy (range, 40.0–108.4 Gy) at a mean time from prior RT to study enrollment of 9.3 ± 5.2 years. The median prescribed dose of SMART was 35 Gy (range, 30–40 Gy) in 5 fractions. Fifteen patients (50%) had high isodose overlap (>80%) between the gross target volume centroid and prior RT field and 4 patients (13.3%) had marginal overlap (20%–80%). The median follow-up time after completion of study RT was 24.4 months (IQR, 23.6–24.9 months). No grade 3+ toxicities related to study treatment were observed. Two-year local control, regional control, and overall survival rates were 96.7%, 76.7%, and 100%, respectively. PROMs scores (EPIC-26, PROMIS-10) were not significantly changed over the study period. Across 160 total fractions, 99.4% of fractions benefited significantly from online adaptive planning to either meet OAR hard constraints (80.0%) or improve PTV coverage by >5% (19.4%). Analysis of intrafraction cine MR imaging revealed a mean duty cycle (% beam-on time) per fraction of 94.3% (range 44–100%), with significant intrafraction motion (duty cycle <90%) noted in 14.4% of fractions.
Conclusion:
The trial met its primary endpoints, demonstrating that SMART is feasible and safe for pelvic reRT of radiorecurrent prostate cancer, with robust local control and minimal high grade toxicity at a median follow up of 2 years. Daily plan adaptation and MR tracking provided considerable benefits in achieving safety goals and improving coverage for several patients. These findings support further study and clinical use of SMART for pelvic reRT and as a salvage therapy for radiorecurrent prostate cancer.