1005 - Acute Toxicity Following Dose-Escalated MRI-Guided SBRT vs. Adapted Dose-Painted MRI-Guided SBRT: A Pooled Comparison of Prospective Trials

08:30am - 08:35am PT

Room 307/308

Presenter(s)

Patrick Courtney, MD, MAS - UCLA David Geffen School of Medicine/UCLA Medical Center, Los Angeles, CA

P. T. Courtney¹, J. Pham¹, T. Romero², D. Karasik³, L. Valle¹, M. Casado¹, M. Ghafarian⁴, J. Calais⁵, K. H. Sung⁶, T. C. Wu¹, J. M. Lamb¹, M. Cao⁷, M. L. Steinberg¹, and A. U. Kishan¹; ¹Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, ²Department of Medicine, University of California, Los Angeles, Los Angeles, CA, ³UCLA Radiation Oncology, Los Angeles, CA, ⁴University of California Los Angeles, Los Angeles, CA, United States, ⁵Ahmanson Translational Theranostics Division, University of California, Los Angeles, Los Angeles, CA, ⁶UCLA, Los Angeless, CA, ⁷Department of Radiation Oncology, University of California San Francisco, San Francisco, CA

Purpose/Objective(s): The MIRAGE trial (NCT04384770) demonstrated improved acute genitourinary (GU) and gastrointestinal (GI) toxicities in patients with prostate cancer treated with aggressive planning target volume (PTV) margin reduction using MRI-guided stereotactic body radiotherapy (MRgSBRT). It is unknown whether adaptive dose painting (increasing dominant intraprostatic lesion (DIL) dose, decreasing the PTV dose) can maintain similar toxicity as compared with homogenous, dose-escalated prostate SBRT, as used on MIRAGE. We compared acute toxicity between patients receiving MRgSBRT on MIRAGE and patients receiving adaptive, dose-painted MRgSBRT on the HEATWAVE trial (NCT06067269).

Materials/Methods:

MIRAGE enrolled patients with localized prostate cancer of any NCCN risk group and utilized non-adaptive, MRgSBRT with a PTV dose of 40 Gy in 5 fractions. HEATWAVE is enrolling patients with NCCN unfavorable intermediate risk prostate cancer and utilizes 5-fraction adaptive, dose-painted MRgSBRT with clinical target volume (CTV), PTV, and DIL doses of 38 Gy, 36.25 Gy, and 50 Gy, respectively. Both trials used 2mm PTV margins. While the primary endpoint is the efficacy of concomitant apalutamide monotherapy, a pre-specified secondary endpoint is acute toxicity, particularly compared to standard MRgSBRT. We compared acute (<90 days from SBRT) physician-scored GU and GI CTCAE toxicity and patient-reported outcomes (IPSS and EPIC-26 bowel) between the two trials with Fisher’s test.

Results: The MIRAGE cohort included 78 patients and the HEATWAVE cohort included 23 patients. Similar proportions of patients took urinary medications at baseline (HEATWAVE 17% v MIRAGE 37%, p=0.08) and had pre-existing GI comorbidities (HEATWAVE 22% v MIRAGE 14%, p=0.51). Physician-scored acute grade =2 GU toxicity rates were significantly higher in HEATWAVE (70% v 24%, p<0.01), as were acute =2 GI toxicity rates (17% v 0%, p<0.01). Rates of clinically significant increases in IPSS (=15) were not significantly different between HEATWAVE and MIRAGE at 1 (13% v 7%, p=0.39) or 3-months (4% v 8%, p=1). Rates of clinically significant decreases in EPIC-26 bowel scores (=12) were not significantly different between HEATWAVE and MIRAGE at 1 (17% v 30%, p=0.29) or 3-months (9% v 24%, p=0.14). Comparison of plan dosimetry did not reveal any dosimetric differences between the two groups.

Conclusion: Patients receiving adaptive, dose-painted MRgSBRT had higher physician-scored acute GU and GI toxicity than those receiving non-adaptive, homogeneous MRgSBRT. However, patient-reported outcomes were similar. Given that similar planning constraints were used and met for both trials, the etiology of this increased acute toxicity is unclear though likely related to currently unmeasured dosimetric endpoints. CTV/PTV dose-reduction alone may not lead to lower toxicity, even with adaptive radiotherapy, when using extremely dose-escalated DIL boosts. Further investigation is warranted as the trial continues to enroll.