Phase I Trial Of MRI-Linac Based Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost For Localized Prostate Cancer (NCT03664193)

Abstract

The treatment paradigm for localized prostate cancer (PCa) can potentially be improved by utilizing recent advances in MRI-based radiation approaches (MRI-Linac) to deliver precise, individualized therapy to areas at greatest risk of disease recurrence while avoiding adjacent normal organs. A phase I feasibility and safety study was designed to deliver MRI-Linac based SBRT with a simultaneous integrated boost (SIB) for PCa patients with dominant intraprostatic nodule (DIN)s on PSMA PET or MRI imaging. The study has completed accrual and we now report our outcomes. From 11/2018- 10/2019, 30 patients with localized PCa and DIN(s) were enrolled. SBRT dose of 36.25 Gy was prescribed. The DIN was defined on PSMA PET and/or MRI and boosted to 37.5 -45 Gy while meeting normal tissue constraints. Use of rectal spacer and PSMA PET was optional. All patients were treated on an MRI-Linac (MRIdian Viewray) with live MRI guidance. Adaptive planning was allowed. Acute toxicity was assessed using CTCAE 5.0. Baseline and follow up sexual, GI and GU patient reported outcomes were assessed. A total of 30 patients (median age 73) were treated on this study, categorized as low, intermediate, and high risk PCa (27%, 63%, and 10% respectively). A mean dose of 40 Gy was delivered to the DIN (range, 37.5 – 45 Gy), demonstrating feasibility of our approach. A total of 23/30 patients had a rectal spacer placed, which did not reduce the maximum rectal dose, but decreased rectal D1cc. Six patients had PSMA PET/MR imaging available. Alterations in prostate volume were recorded on MR. The median prostate volume by the end of treatment increased by 6.1 cm3 corresponding to a significant volumetric change of 20.8% compared to baseline (Range -3.9% to 30.5%). As a result of these volumetric changes, the D95 decreased by median of 9.6%. There were no G3 or higher acute treatment related toxicities. Acute G2 GU and GI toxicity was noted in 27% (n = 8) and 7% (n = 2) of patients, respectively. Evaluable patients (22 out of 30) demonstrate that 91% have IPSS scores back or below baseline (+/- 1 pt) by 3 months follow up, with no significant change in the EPIC urinary or bowel domain. MRI-Linac based SBRT with SIB is a feasible and safe approach to treat localized PCa, maximizing dose to regions at greatest risk while minimizing toxicity to adjacent organs. MRI imaging during treatment demonstrates that the prostate undergoes enlargement and subsequent contracture during SBRT, suggesting size fluctuations must be accounted for. The addition of PSMA PET/MR improves both staging and delineation of the DIN, and may be an elegant partner to MRI-Linac based prostate SBRT with SIB. A Phase II study to test the efficacy of PSMA PET/MR based, MRI-Linac SBRT with SIB with option of adaptive replanning, has received funding to open in the near future as a subsequent protocol.