Purpose/Objective(s) Magnetic resonance (MR)-guided stereotactic body radiation therapy (MR-SBRT) facilitates dose escalation to oligometastatic targets in close proximity to gastrointestinal organs-at-risk (OARs) given excellent soft tissue visualization, automatic beam gating, and on-table adaptive workflow to account for interfraction anatomic change. The objective of this study was to report the outcomes of patients treated with MR-SBRT in the infra-diaphragmatic (ID) region to characterize dose-response relationships associated with tumor control, characterize patterns of failure, and report on long-term treatment-related toxicities. Materials/Methods We retrospectively evaluated patients ≥18 years old treated for up to 5 oligometastases (OM) treated with MR-SBRT between May 2018 and August 2023. Patients were categorized as oligorecurrent, oligoprogressive, or oligopersistent. Local control (LC) and distant progression-free survival (DPFS) from the time of MR-SBRT were calculated using the Kaplan-Meier method. Results In total, 143 patients were prescribed a median 50 Gy in 5 fractions (Range: 25-60 Gy; 1-6 fractions) to 181 targets over 170 SBRT courses. On-table treatment adaptation was required for 635/860 (73.8%) of delivered fractions. The most common primary tumors were lung (37.7%), colorectal (18.2%), and gynecologic (14%). Target lesions mainly included lymph nodes (LNs) or peritoneal implants (39.2%), adrenal glands (30.4%), and liver (21%). Most patients (46.1%) presented with oligorecurrent disease, followed by oligoprogressive (42.0%) and oligopersistent disease (11.9%). The 1-, 2-, and 3-year actuarial LC rates were 89.3% (95% CI: 84-94.6%), 78% (95% CI: 69.7-86.1%), and 73.1% (95% CI: 63.1-83.1%), respectively. Longer median DPFS trended towards significance for non-oligoprogressive vs. oligoprogressive OM (10.9 vs. 5.9 months), P = 0.062. The prescribed dose for colorectal and non-colorectal cancers was similar; the prescribed median BED10 was 101.1 Gy (Range: 38.9-225.5) vs. 103.2 Gy (Range: 39.6-184.2), respectively, and 2-year LC was 77.7% (95% CI: 60-94%) and 77.6% (95% CI: 68.2-87%), respectively. Almost all patients with local failure also had concurrent distant failure (DF) (21/22, 95%). Grade 3 or higher late toxicity was uncommon, with a 1 to 3-year actuarial rate of 1.4% (95% CI: 0-4.1%). Conclusion In this large and heterogenous cohort of patients with ID metastases treated with ablative intent MR-SBRT, we found high and durable rates of local control regardless of histology, modest DPFS rates, and an excellent toxicity profile. Adaptive replanning was frequently required due to anatomically unfavorable target lesion locations. Expectedly, DF continues to be an important issue in the management of oligo-progressive patients.

Background: Neoadjuvant chemotherapy coupled with radiotherapy (RT) may provide survival benefits when compared to upfront surgery in patients with borderline resectable pancreatic cancer. It is hypothesized that delivering precise, ablative doses of radiation allows for improved outcomes without increasing significant treatment-related toxicity. The purpose of the present study is to evaluate the safety and feasibility of surgical resection after neoadjuvant ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) in patients with pancreatic cancer.

This isthe first evaluation of IAC effects on predicted GI OAR dose for 5-fx CT- vs. MR-guided SBRT. Although VMAT arcs facilitated higher target coverage in the initial CT plans, GI OAR constraint violations were observed in 85-88% of CT/MR plans. Although on-table adaptive replanning is routine on MR-guided Linacs it is not commonly available on CT-guided Linacs. As such, ablative 5-fx SBRT delivered with CT guidance is expected to result in significant toxicity due to exceeding GI OAR constraints for most delivered fractions.

This study represents the first patterns of LRF analysis after ablative 5-fraction SBRT for PDAC. Although EC is not currently endorsed by published pancreas SBRT guidelines, our low LRF incidence especially involving the CA/SMA demonstrates that EC should be considered, even when delivering ablative dose. Furthermore, given that nearly all LRF were M or OOF we have considered expanding our institutional elective volumes. While the optimal EC dose is uncertain, 33-35 Gy appears effective in limiting IF LRF and therefore has been standardized within ongoing ablative SBRT trials for PDAC at our institution.

Purpose/Objective(s) Despite frequent dosimetric advantages to proton therapy over photon therapy in head and neck (H&N) cancers, there is concern for end of range biologic dose enhancement and subsequent increased mucosal toxicity with proton therapy. Herein, we evaluated differences in mucosal FDG avidity on post-treatment FDG PET-CTs between proton and photon therapy patients, as persistent activity is a surrogate for residual mucosal toxicity. Materials/Methods The cohort comprised ten proton and ten photon patients who received ≥40 Gy to a mucosal oropharyngeal site with curative intent after initial surgery and who remained loco-regional disease free ≥6 months post-treatment. All patients underwent follow-up PET-CT scans 3 months post-radiotherapy. Images centered over the treated primary were acquired 60 minutes after intravenous administration of 10 mCi of FDG. CT-based attenuation correction was applied to the data sets. The PET-CTs were fused to the planning CT using deformable registration using a commercial treatment planning system (TPS). Contours were generated in the deformed PET datasets using a 1.5 × LiverSUV threshold, i.e., 50% above background; these uptake areas were later intersected with the mucosal CTV plus a 5 mm margin to create the region of interest (ROI). SUV maximum (SUVMAX) values based on lean body mass were extracted for this ROI. Results The SUVMAX values found in the post-treatment PET-CTs in the intersected ROI for the proton group ranged between 7.08 and 9.38, whereas in the photon group, SUVMAX values ranged from 3.89 and 6.49. The likelihood of having SUVMAX values above the 1.5 × LiverSUV threshold was higher in the proton group (4 of 10 patients) compared to the photon group (2 of 10 patients). Clinically, an ulcer was visible in one proton patient at the area of FDG avidity. Conclusion Our results indicate that post-radiotherapy FDG avidity was more commonly observed in proton patients, which correlated with clinical mucosal toxicity.

Purpose/Objective(s)Implanted metallic devices are a potential contraindication to MR-guided radiotherapy (MRgRT). The safety and feasibility of treating patients with a cardiac implantable electronic device (CIED), such as a pacemaker/defibrillator/loop recorder, is not well understood. We developed an institutional CIED MRgRT workflow for patient triage/evaluation and treatment on a 0.35 T MR Linac.Materials/MethodsPatients (including pacemaker dependent) with MR-compatible CIEDs were prospectively evaluated according to an institutional MRgRT CIED workflow. This workflow includes prior to simulation: (1) MR patient screening form at consultation to identify CIED; (2) Medical necessity for MRgRT determined by clinician and approved by MRgRT director. If medical necessity not established, patient is triaged to non-MR RT; (3) Cardiologist to complete CIED programming orders; (4) Medical physicist to verify that MR-compatible CIED matches vendor's records; (5) Chest X-ray to be reviewed to ensure no extenders, adaptors, or abandoned leads and to confirm radiopaque CIED ID; (6) Patient to consent for off-label CIED according to risk assessment. The workflow for MRgRT treatment includes: (1) Crash cart, pulse oximetry, and electrocardiogram availability/use; (2) Cardiology present; (3) CIED pacemaker and defibrillator interrogated for lead impedance, battery voltage, and pacing threshold; (4) CIED programmed according to orders; (5) Vitals monitored during MRgRT using in-vault camera; (6) Post-treatment, CIED returned to normal pacing and interrogated. (7) All patients monitored for cardiac events throughout the course of treatment.ResultsFive different CIED models in 12 patients (9 pacemaker, 2 loop recorder, 1 defibrillator) were encountered in patients with cancers of the pancreas (5), kidney (2), lung (2), adrenal (1), bile duct (1), oligometastases (1). Patients received a median dose of 50 Gy (range 25-60 Gy) in 5 fractions (fx) (range 1-5); 80% of patients were adaptively replanned on-table. Maximum CIED dose was < 2 Gy for all patients. No intra- or interfraction CIED change was noted for lead impedance, pacing threshold voltage, and battery voltage. With median follow up of 5.2 months, no patient experienced a cardiac event or CIED malfunction.ConclusionWe developed a thorough and efficient workflow for management of CIED in patients receiving MRgRT. Safety of consecutive use of MR imaging up to 6 sessions (i.e., simulation and treatment) was shown. Under controlled conditions and monitoring, low-field MRgRT, with cumulative device dose < 2 Gy, may be used without adverse events in patients with CIEDs, including high-risk patients. Ultra-hypofractionation (1-3 fxns) may be considered to further reduce patient risk and departmental resources.

Purpose/Objective(s) Ablative RT doses ∼100Gy BED10 are associated with improved overall survival (OS) in patients with locally advanced unresectable pancreatic cancer (LAPC), but the optimal fractionation scheme remains unknown. Materials/Methods We performed a retrospective analysis of consecutive LAPC patients treated at 2 high-volume institutions with either 50 Gy in 5 fractions using a 0.35T MR Linac and online adaptive replanning between 2018-2021 or 67.5-75 Gy in 15-25 fractions using CBCT guidance and selective offline adaptive replanning between 2016-2019. All were treated with breath hold or gating. Elective nodal coverage was used in 94%. Clinical characteristics between the groups were compared using Fisher's exact test. Freedom from local progression (FFLP) by RECIST and OS were estimated from time of RT with the Kaplan-Meier method. Log-rank test and Cox proportional hazards regression model were used for univariate (UVA) and multivariate (MVA) analyses. Results 183 patients were evaluated including 62 (34%) treated with 50 Gy in 5 fractions, 23 (123%) treated with 67.5 Gy in 15 fractions, and 98 (54%) treated with 75 Gy in 25 fractions. Median age was 67 years (range 35 to 91), 53% were male, 72% had a head tumor location, 81% were T3/4 with a median tumor size of 3.8 cm (range 1.4-7.4 cm) and 38% were lymph node positive. Patients receiving 5 fractions were more likely to be N0 than patients receiving 15-25 fractions (69.3% vs 44.6%, p=0.0219), and there were no other clinical differences between the groups. 98% received induction chemotherapy for a median of 3.9 months (FOLFIRINOX 61%, Gemcitabine/Nab-paclitaxel 29%, other 10%). Median follow-up was 38 months. Median FFLP and OS were 31 and 18 months, with 2-yr FFLP and 2-yr OS of 62.9% (95%CI 47.9 – 69.3%) and 36.2% (26.0 – 40.9%), respectively. There were no significant differences in FFLP (HR= 1.493, 95%CI 0.8030 – 2.775, p=0.1598) or OS (HR=1.321, 95%CI 0.8835 – 1.974, p=0.1580) between patients receiving 5 vs 15-25 fractions, respectively, on UVA. Likewise, after adjusting for T stage, nodal status, tumor size, chemotherapy type and duration, there were no significant differences in OS between the groups on MVA (HR=1.234, 95%CI 0.8151 – 1.833, p=0.3070). The rate of grade 3+ GI bleeding was 4.8% and 8% (p=0.5476) in patients receiving 5 vs 15-25 fractions, respectively. Conclusion In appropriately selected LAPC patients, ablative RT (BED10 ∼100 Gy) in 5 fractions delivered with MR guidance and online adaptive replanning or 15-25 fractions delivered with CT guidance and selective offline adaptive replanning both appear to achieve excellent efficacy and minimal severe toxicity. Choice of fractionation scheme should be based on anatomical considerations and available technology.

Purpose/Objective(s) MR-guided radiotherapy (MRgRT) provides longitudinal MR images during RT, and enables the evaluation of potential imaging biomarkers of treatment response (TR). We investigated whether interfraction tumor volumetric changes correlated with ultimate radiographic response. Materials/Methods 131 patients underwent daily adaptive MRgRT of the pancreas (n=71), adrenal (n=27), abdominal lymph node (LN) (n=19), and pelvic LN (n=14) to a median of 50 Gy/5 fractions (fxs). For each adaptive fx, the simulation GTV was compared to the daily GTV on the 0.35 T TRUFI MR. GTV change (ΔGTV) was quantified as the % difference in GTV of the adapted fx compared to simulation. To ensure robustness, a minimum ΔGTV > ±1 cc was required for TR-correlation on post-RT diagnostic MR. Patients were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), using RECIST criteria, and TR was correlated to fx with the largest ΔGTV. Results Median follow up was 22.5 months. Numerically (not statistically significant) the largest interfraction ΔGTV for the entire cohort was observed at fx 3 (14.2%) compared to 6.8, 10.2, 8.9, and 13.1% for fxs 1, 2, 4, and 5, respectively. For pancreas, adrenal, abdominal LN, and pelvic LN, the median ΔGTV at fx 3 (ΔGTVfx3) was -5.1, 20.8, 27.5, and 3.4%, respectively; meaning GTV increased, on average, for all sites except pancreas. ΔGTVfx3 as a function of TR is displayed in the Table. ΔGTVfx3 for pancreas and pelvic LN was <10%. For adrenals achieving post-RT CR, PR, SD, larger ΔGTVfx3 were observed, with median of 23.8, 20.8, and 26.3%, respectively, with extreme case of 41% increase in a patient achieving a subsequent CR. For PD adrenal lesions, the ΔGTVfx3 is 0. These findings putatively suggest an acute SBRT-related inflammatory response resulting in subsequent disease stability or regression. In contrast, for abdominal LN, no such significant ΔGTVfx3 is noted for CR, PR, or SD, but for PD, the ΔGTVfx3 increases substantially to 39.1%. Conclusion Daily adaptive MRgRT enabled interfraction tracking of ΔGTV that was retrospectively correlated to TR. Numerically, we observed the greatest ΔGTV at fx 3. However, this change was seen primarily in adrenal and abdominal nodal lesions, and not other sites. The significance of this change is non-uniform, in that for adrenal lesions, responders were more likely to have volumetric increase, whereas for abdominal LN, progressors were more likely to have volumetric increase. These preliminary findings are being rigorously tested through a retrospective, multi-observer blinded contouring exercise, and also being extended to other disease sites, prior to formulating a clinically actionable hypothesis.

Purpose/Objective(s) Several variables result in patient treatment delays in day-to-day radiotherapy operations that may cause patient dissatisfaction, inefficient machine utilization, and ad-hoc scheduling practices. Such challenges are magnified in larger centers offering multi-technology treatment platforms. Conventional approaches to manage machine times by examining beam-on time, or tracking the number of patients treated per day on each unit often, fail to provide a realistic picture for departmental capacity and staffing. As a result, we initiated a wearable tracking device project to better evaluate and document total time spent by each patient at each treatment unit for every fraction. Materials/Methods In 2022, a patient-specific, Real-Time Location System (RTLS) wearable device project was implemented to examine patient throughput, flows and delays within a single institution. The RTLS device is a small, clip-on location transponder provided to every patient at check-in for each visit. The total treatment time (TTT) required for the completion of each fraction was obtained by subtracting vault entry times (Ventry) from vault exit times (Vexit) as recorded by RTLS transponder sensors at the entrance of each vault. These times were then compared to scheduled Ventry, Vexit, and TTT for each fraction to examine variances. Results During a 3-week period dedicated to testing feasibility, a total of 2,298 fractions were delivered using 7 photon and 3 proton external beam radiation units. RTLS tracking data was successfully obtained for 678 fractions (30% of total fractions). Overall, 63.8% of tracked fractions started more than 5 min after their scheduled time and 31.2% of tracked fractions were completed after their scheduled allotted time. Median differences between scheduled and actual times for all machines were -10.1 min (-17.0 to 6.8 min), -6.6 min (-32.2 to 5.8 min), and 5.0 min (-19.0 to 8.0 min) for Ventry, Vexit and TTT, respectively. When comparing photon versus proton units, photon patients experienced longer delays with vault entry times (median: -13.0 vs -8.0 min). Conclusion Initial data support feasibility with 1/3 of all patients successfully tracked using RTLS within only 3 weeks of its implementation. The acquired baseline data demonstrate considerable variance between scheduled and actual times for radiation delivery, providing early insight for opportunities to improve efficiency and treatment timeliness. Future efforts will focus on methods to increase RTLS usage to over 90% through patient and staff education. The next phase of RTLS implementation will also examine the root causes of delayed fractions for schedule optimization and capacity modelling.

PBT achieves considerably smaller volumes of pelvic OARs receiving low and moderate dose compared to VMAT, with AP/PA plans achieving the best overall sparing and lowest probability of HT3+. Clinical outcomes of PBT for AC remain poorly understand with little published data, and prospective evaluation of this novel treatment approach is needed.

MR real-time visualization of the patient's intrinsic laryngeal muscles during MRgRT provides a method of gating treatment during patient swallowing. Robust intrafraction target tracking appears to enable higher confidence in reducing the treatment volume for early larynx cancers such that improvements in preservation of voice quality and deglutition capabilities are possible without sacrificing local control. A clinical trial is planned to examine such volume reduction and its effect on patient quality of life and function.

BD enhancement was observed at the periphery of mucosal targets in these patients. An additional study is needed to evaluate the correlation of this dose enhancement with clinical/radiologic outcomes. In the future, use of additional beam angles and/or incorporating LET in treatment planning may mitigate this effect.

To our knowledge, this is the first analysis of cumulative TV dose from 5-fraction SMART for PCa. While use of ENI is controversial, moderate and statistically significant correlations were noted between LRF and ENI, in addition to PTV volume and maximum dose. Additional investigation is warranted to better understand whether specific dose thresholds exist for gross disease and electively treated volumes with respect to long-term LC and OS.

The greater relative size reduction in parotids versus SMGs was consistent with previous photon data. The mean increase in SMG volume could represent post-treatment functional compensation in preserved glands, but this requires additional investigation. Also, determination of the effect of proton dose on salivary gland volume change requires further analysis. Currently, no conclusions can be drawn whether salivary glands are equally or differentially sensitive to proton therapy relative to photon therapy.