Margin call.

Top Line: Do smaller margins result in less toxicity from prostate SBRT?

The Study: MIRAGE was a single-center (UCLA), randomized trial of 156 patients treated with SBRT for prostate cancer. They were randomized to treatment on a standard LINAC with CT simulation and CT image guidance or a MRI-LINAC with MRI simulation (0.35T) and daily MRI image guidance. Patients in the standard arm had fiducial markers placed while those in the MRI arm did not. All patients had diagnostic 1.5-3T MRI of the prostate that was fused with the simulation CT or MRI for target delineation. The trial was based on the assumption that the advantages of MRI-guided RT allow a reduction in the PTV margin from 4mm to 2mm. These include better soft tissue delineation using MRI-simulation, true soft tissue alignment (rather than fiducial alignment) daily, and greater spatial certainty with the ability to obtain cine MRI images during treatment delivery. In both arms the PTV was prescribed 40 Gy in 5 fractions, and providers were allowed to deliver a SIB to the dominant nodule, treat elective nodes, or give ADT at their discretion. Rectal hydrogel spacer was used in 44%. The rate of acute grade 2+ CTCAE GU toxicity was significantly lower in the MRI arm (24.4% v 43.4%). The rate of acute grade 2+ GI toxicity was also lower (0% v 10.5%). At 1 month, patient-reported GI and GU outcomes were less severe in the MRi arm, but these differences were not significant at 3 months.

TBL: Smaller PTV margins reduce acute toxicity from prostate SBRT. The question is what techniques are necessary to reduce margins without affecting tumor control? In MIRAGE, MRI-guided RT on a MRI-LINAC was necessary to use smaller margins. Could smaller margins be used with CT and fiducial tracking? Longer follow up will tell if late toxicity is reduced or if smaller margins affect the risk of recurrence. | Kishan, JAMA Oncol 2022