## 6 Novel Techniques, Dose Escalation and Safety in SBRT  
Magnetic-resonance-guided radiation therapy utilization is rapidly expanding, providing intra-fraction visualization, adaptive re-planning and advanced motion management, which has allowed the delivery of ultra-hypoffractionated regimens. A recent Phase I clinical trial from Washington University [58], Stereotactic MRI-Guided Online Adaptive Radiation Therapy (SMART) trial, evaluated the safety and feasibility of MRI-guided adaptive SBRT for ten patients with oligometastatic ovarian cancer to a dose of 35 Gy in five fractions (BED\({}_{10}\) 59.5) with optional dose escalation up to 50 Gy in five fractions (BED\({}_{10}\) 100), provided organ-at-risk (OAR) constraints were met. Adaptive RT allows for real-time changes to radiation plans as MRI guidance improves visualization of tumors and surrounding OARs. The primary endpoint of this study was feasibility. The average on-table time was 69 and 54 min for plans that were adapted and not, respectively. This is comparable to other radiotherapy procedures, like brachytherapy, and all plans were able to be executed. Fifty-eight percent of fractions were adapted in this study, with the majority adapted for reversal of OAR constraint violations, which mostly occurred in the abdomen or pelvis. A single grade \(\geq\)3 toxicity was observed (duodenal ulcer). Local control at 3 months was 94% and maintained at 1 year. Median PFS was 10.9 months and systemic therapy-free survival was 11.5 months. Further research and technological advances in precision delivery of higher BEDs, while maintaining OAR constraints, could theoretically lead to increased rates and duration of local control, but the effect on overall survival from out-of-field progression is still unknown. Many studies report that SBRT is very well tolerated, with predominantly mild grade 1-2 gastrointestinal-related toxicities [13; 14; 17; 18; 22; 26; 27; 28; 29]. Grade 3-4 toxicities were noted in 2.6-10% of patients within 7/16 studies in the systematic review by [PERSON] et al. [12] that reported grade > 3 toxicities, and no grade 5 toxicities were reported. Acute grade 3 toxicities included duodenal ulcer, esophagitis, hemorrhagic visits, enterovaginal fistula and diarrhea. Late grade 3 toxicities included urethral stricture, ileus, enterocolitis, and small bowl obstructions. Grade 4 toxicities included neutropenia, hypokalemia, hyperbilirubinemia and late rectovaginal fistulas. However, [PERSON] et al. [18] noted a single grade 5 duodenal ulcer in a patient retreated with SBRT for out-of-field recurrence to the porta hepatis (18 Gy in three fractions). Therefore, a second course of SBRT in overlapping treatment areas should be considered with caution, especially in abdominal and pelvic oligometastases. In the study by [PERSON] et al. [22] 16 out of a cohort of 40 patients with endometrial and ovarian oligometastases had a repeat course of SBRT for synchronous or metachronous oligometastatic spread outside of the previously radiated field. This study showed safety in the repeat course of SBRT with no grade \(\geq\) 2 adverse events. Repeat SBRT did not lead to a survival benefit when compared with patients who developed immediate polymetastatic spread, in contrast to lung oligometastatic disease from colorectal primary cancer with sequential oligometastases following SBRT receiving a second course of SBRT, leading to a significantly longer cancer specific survival [59].