1158 - Stereotactic Magnetic Resonance (MR)-Guided Adaptive Radiotherapy (SMART) for Liver Metastases near Critical Organs at Risk: A Phase I Trial and Supplemental Cohort for Feasibility and Safety
Presenter(s)
N. A. Saeed1, P. P. Patel2, D. Ferguson3, S. Tanguturi4, M. A. Huynh5, H. Elhalawani2, K. J. Fitzgerald6, R. H. Mak7, H. J. Mamon8, Z. Han3, J. E. Leeman2, and R. van Dams8; 1Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 2Department of Radiation Oncology, Mass General Brigham, Harvard Medical School, Boston, MA, 3Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 4Department of Radiation Oncology, Mass General Brigham Cancer Institute, Boston, MA, 5Department of Radiation Oncology, Brigham and Women’s Hospital / Dana-Farber Cancer Institute, Boston, MA, 6Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, NY, 7Department of Radiation Oncology, Mass General Brigham/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 8Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA
Purpose/Objective(s): Stereotactic magnetic resonance-guided adaptive radiotherapy (SMART) allows for more precise delivery of radiation due to improved soft tissue contrast, daily plan adaptation, and real-time motion gating without fiducials. Given significant movement with the respiratory cycle, motion management is critical in treating larger liver tumors near sensitive organs at risk (OARs). There is limited data on the role of SMART in treating liver metastases.
Materials/Methods: We conducted a prospective phase I trial of SMART without gadoxetate disodium contrast for liver metastases with primary endpoints of feasibility and safety. Patients treated with SMART on a MRIdian linear accelerator (ViewRay Systems, Inc) for liver metastases off protocol were also included in the analyses. Clinical outcomes included overall survival (OS), local and regional control (LC, RC), and grade 3 toxicities (biliary, gastrointestinal [GI], and hepatic) based on the Common Terminology Criteria for Adverse Events v5. We compared dosimetric data for OAR & planning target volume (PTV) coverage between original, predicted, and adapted treatment plans.
Results: Our cohort included 73 patients (N=10 phase I, N=63 supplemental), with 77 different treatment courses. The most common primary histologies were colorectal (31%) & pancreatic adenocarcinoma (12%). 51% were female. Median age at time of treatment was 67 years. 42% had multiple liver lesions at time of treatment and 5% received prior liver radiation. BED10 ranged from 37.5—100 Gy, with 78% receiving a BED10 of 100. 99% received 5 fractions and 78% received 50 Gy. 8% had multiple metastases treated in a single course. Treated lesions were most commonly in segment 4 (22%), followed by 5 (19%), and 2 (14%). Median pre-treatment tumor size was 2.9 cm (interquartile range [IQR] 1.9-4.6). Only one patient experienced grade 3 biliary toxicity and one had grade 3 bowel toxicity, both in the supplemental cohort. None had grade 3 hepatic toxicity. No grade 4 or 5 events were observed. Median OS was 35.7 months (95% confidence interval [CI] 25.4-51.3) with a median follow up of 24.0 months. Median LC was 24.2 months, and median RC was 9.2 months. 1-year OS, LC, and RC were 70.9% (95% CI 58.5-80.2), 75.3% (95% 62.7-84.2), and 47.6% (95% CI 35.3-58.8) respectively. 1-year LC was significantly worse for tumor sizes >3 cm vs <3 cm (57.2% vs 91.3%, p=0.005). Regarding dosimetry, 50.6% and 38.1% of predicted plans violated a luminal GI OAR 0.03cc and 0.5 cc constraint, respectively; this improved to 0% and 0% after adaptation. Adaptation improved PTV coverage for 66% of fractions.
Conclusion: SMART for liver metastases near luminal GI structures is feasible and associated with promising local control and minimal toxicity. Plan adaptation helps achieve compliance with OAR constraints and in many cases substantially improves PTV coverage. These findings help support the use of SMART in patients with high-risk liver metastases that are larger and in traditionally challenging locations.