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Simple Summary: Magnetic resonance-guided radiotherapy (MRgRT) is expanding worldwide thanks to advances in soft tissue imaging, continuous visualization of the target and normal organs-at-risk during treatment, automated intelligently gated beam delivery within predefined targeting boundaries, and on-table adaptive replanning, all of which permit improved treatment efficacy, toxicity reduction, and shortened fractionation regimens. This, however, is still a nascent technology which can be more time- and resource-intensive than standard radiotherapy, and hence its optimal utilization and deployment remain in constant flux and evolution. We retrospectively analyzed our institutional MRgRT utilization across 823 treatment courses over a 6-year period, which predominantly included abdominal and pelvic tumors treated with dose-escalated ultra-hypofractionation. Background/Objectives: Over the past decade, significant advances have been made in image-guided radiotherapy (RT) particularly with the introduction of magnetic resonance (MR)-guided radiotherapy (MRgRT). However, the optimal clinical applications of MRgRT are still evolving. The intent of this analysis was to describe our institutional MRgRT utilization patterns and evolution therein, specifically as an early adopter within a center endowed with multiple other technology platforms. Materials/Methods: We retrospectively evaluated patterns of MRgRT utilization for patients treated with a 0.35-Tesla MR-Linac at our institution from April 2018 to April 2024. We analyzed changes in utilization across six annualized periods: Period 1 (April 2018–April 2019) through Period 6 (April 2023–April 2024). We defined ultra-hypofractionation (UHfx) as 5 or fewer fractions with a minimum fractional dose of 5 Gy. Electronic health records were reviewed, and data were extracted related to patient, tumor, and treatment characteristics. Results: A total of 823 treatment courses were delivered to 712 patients treated for 854 lesions. The most commonly treated sites were the pancreas (242 [29.4%]), thorax (172; 20.9%), abdominopelvic lymph nodes (107; 13.0%), liver (72; 8.7%), and adrenal glands (68; 8.3%). The median total prescribed dose of 50 Gy in five fractions (fxs) was typically delivered in consecutive days with automatic beam gating in inspiration breath hold. The median biologically effective dose (α/β = 10, BED10) was 94.4 Gy with nearly half (404, 49.1%) of all courses at a prescribed BED10 ≥ 100 Gy, which is widely regarded as a highly effective ablative dose. Courses in Period 6 vs. Period 1 more often had a prescribed BED10 ≥ 100 Gy (60.2% vs. 41.6%; p = 0.004). Of the 6036 total delivered fxs, nearly half (2643, 43.8%) required at least one fx of on-table adaptive radiotherapy (oART), most commonly for pancreatic tumors (1081, 17.9%). UHfx was used in over three quarters of all courses (630, 76.5%) with 472 (57.4%) of these requiring oART for at least one fraction. The relative utilization of oART increased significantly from Period 1 to Period 6 (37.6% to 85.0%; p < 0.001); a similar increase in the use of UHfx (66.3% to 89.5%; p < 0.001) was also observed. The median total in-room time for oART decreased from 81 min in Period 1 to 45 min in Period 6, while for non-oART, it remained stable around 40 min across all periods. Conclusions: Our institution implemented MRgRT with a priority for targeting mobile extracranial tumors in challenging anatomic locations that are frequently treated with dose escalation, require enhanced soft-tissue visualization, and could benefit from an ablative radiotherapy approach. Over the period under evaluation, the use of high-dose ablative doses (BED10 ≥ 100 Gy), oART and UHfx (including single-fraction ablation) increased significantly, underscoring both a swift learning curve and ability to optimize processes to maximize throughput and efficiency. [ABSTRACT FROM AUTHOR]

Background: Emerging data suggest ablative radiation therapy (A-RT) substantially improves long-term local control (LC) for inoperable pancreatic ductal adenocarcinoma (PDAC) and potentially overall survival (OS). However, routine delivery of ablative dose has been limited by conventional image guidance and daily variability in nearby gastrointestinal organs-at-risk. Materials/methods: A single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) on a 0.35T-MR Linac from 2018-2021 without fiducial markers and in breath hold. Elective volume coverage was used in 80.6% of patients and became routine in late 2019 including a margin around the gross tumor volume (GTV), celiac artery, and superior mesenteric artery. RECIST 1.1 and CTCAE v5 criteria were used to evaluate response and toxicity, respectively. Results: 62 patients were evaluated with median age 66 years (range 35-91) and nearly all ECOG 0-1 (96.8%). Tumor location was the head of pancreas (88.7%), otherwise the body (11.3%). Median tumor size was 3.8 cm (range 1.5-6.9). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%) or medically inoperable (4.8%). Median CA19-9 at diagnosis was 168.7 U/mL (range, 1.2-12,868.6). All patients received induction chemotherapy for a median 4.2 months (range, 0.2-13.3), usually FOLFIRINOX (69.4%) otherwise gemcitabine/nab-paclitaxel (24.2%) or gemcitabine alone (6.5%). Median prescribed dose was 50 Gy (range 40-50) and median biologically effective dose (BED10) was 100 Gy10. Therapy after A-SMART included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). 13/14 resected patients had negative margins (92.9%). Median follow-up was 18 months (range 6-44 months) from diagnosis. Median and 2-year estimated LC was not reached and 87.7%, respectively. Median and 2-year estimated progression-free survival (PFS) was 16 months and 25.7%, respectively. Median and 2-year estimated OS was 23 months and 45.5%, respectively. No significant LC/OS difference was observed between surgery versus no surgery after A-SMART. % CA19-9 change after induction chemotherapy was a statistically significant prognostic factor for OS (hazard ratio 1.005; 95% confidence interval 1.001-1.009; P=0.008). Acute/ late grade 3+ toxicity rates were 4.8%/4.8%, respectively. Conclusions: To our knowledge, this is the first analysis of 5-fraction A-SMART for inoperable PDAC in which all patients first received chemotherapy. This novel strategy appears to substantially improve the therapeutic ratio, achieve long-term OS for a subset of patients even without subsequent surgery, and allow for a potentially lengthy chemotherapy-free interval after A-SMART. [ABSTRACT FROM AUTHOR]