Treatment Delivery Gating of MRI-Guided Stereotactic Radiotherapy for Prostate Cancer: An Exploratory Analysis of a Phase III Randomized Trial of CT-Vs. MR-Guided Radiotherapy (MIRAGE).

Compared to CT-guided radiotherapy, MRI-guided radiotherapy (MRgRT) has been shown to reduce acute physician-scored and patient-reported gastrointestinal and genitourinary (GU) toxicities associated with prostate stereotactic body radiotherapy (SBRT) in the MIRAGE randomized trial (NCT04384770). We hypothesize that real-time intrafraction tracking/gating is important and is a critical enabler of aggressive margin reduction with MRgRT.

79 patients received MRgRT on the MIRAGE trial with a planning margin of 2mm around the prostate and proximal seminal vesicles, which were treated to 40 Gy in five fractions on an MR-Linac. Tracking was performed at 4 frames/second in the sagittal plane during treatment with a gating boundary of 3mm for automatic beam hold. An in-house tool was developed to extract treatment time and beam gating status based on treatment logs and real-time cine images. The ratio of the time that the target was within the gating window/total time of target inside or outside the gating boundary was defined as the duty cycle (DC). Target contours were extracted from each frame of tracking and overlaid to create a motion-convolved target occupancy map. Minimum isotropic expansions of the prostate to cover 85%, 90% and 95% of the intrafraction motion were calculated with and without gating.

Median treatment time per fraction including image guidance procedure and beam delivery was 24.3 min (IQR: 22.2-27.7 min). The median time for image guidance 5.4 min (IQR: 4.2-6.7 min). A total of 391 treatment fractions were analyzed and the median DC per fraction was 0.974 (IQR: 0.926 -0.983). 89 (22.8%) and 35 (9.0%) of fractions had DC<90% and <80%, respectively, corresponding to 50/79 (62.3%) and 24/79 (30.4%) of patients having at least one fraction with a DC<90% and <80%, respectively. The minimum duty cycle of all fractions was lower among patients with grade ≥2 GU toxicity compared to those with grade 0-1 GU toxicity (mean 79.8% vs. 85.9%, p = 0.06). The proportion of patients with grade ≥2 GU toxicity was also greater in patients with a minimum gating cycle <80% (37.5% vs. 18.2%, p = 0.06). Gating significantly decreased the minimum isotropic expansion of the prostate to cover 85%, 90% and 95% of the intrafraction motion (p<0.0001 for all). Prostate intrafraction motion tended to be along the bladder-rectum axis secondary to bladder filling, rectal gas and bulk motion. Fractions with large prostate motion were mostly stochastic.

A large fraction (30%) of patients had at least of one treatment fraction with DC<80%, which correlated with increased acute GU toxicity. Gating effectively reduces the expansion needed to cover prostate intrafraction motion, and is necessary for real-time motion management given the unpredictable nature of prostate motion.

International journal of radiation oncology, biology, physics. 2023 Oct 01 [Epub]

T M Ma, J P Neylon, R R Savjani, D Low, M L Steinberg, M Cao, A U Kishan

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA., UCLA, Los Angeles, CA., Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA., Department of Radiation Oncology, UCLA, Los Angeles, CA.