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Introduction: The ability to dynamically adjust target contours, derived Boolean structures, and ultimately, the optimized fluence is the end goal of online adaptive radiotherapy (ART). The purpose of this work is to describe the necessary tests to perform after a software patch installation and/or upgrade for an established online ART program., Methods: A patch upgrade on a low-field MR Linac system was evaluated for post-software upgrade quality assurance (QA) with current infrastructure of ART workflow on (1) the treatment planning system (TPS) during the initial planning stage and (2) the treatment delivery system (TDS), which is a TPS integrated into the delivery console for online ART planning. Online ART QA procedures recommended for post-software upgrade include: (1) user interface (UI) configuration; (2) TPS beam model consistency; (3) segmentation consistency; (4) dose calculation consistency; (5) optimizer robustness consistency; (6) CT density table consistency; and (7) end-to-end absolute ART dose and predicted dose measured including interruption testing. Differences of calculated doses were evaluated through DVH and/or 3D gamma comparisons. The measured dose was assessed using an MR-compatible A26 ionization chamber in a motion phantom. Segmentation differences were assessed through absolute volume and visual inspection., Results: (1) No UI configuration discrepancies were observed. (2) Dose differences on TPS pre-/post-software upgrade were within 1% for DVH metrics. (3) Differences in segmentation when observed were small in general, with the largest change noted for small-volume regions of interest (ROIs) due to partial volume impact. (4) Agreement between TPS and TDS calculated doses was 99.9% using a 2%/2-mm gamma criteria. (5) Comparison between TPS and online ART plans for a given patient plan showed agreement within 2% for targets and 0.6 cc for organs at risk. (6) Relative electron densities demonstrated comparable agreement between TPS and TDS. (7) ART absolute and predicted measured end-to-end doses were within 1% of calculated TDS., Discussion: An online ART QA program for post-software upgrade has been developed and implemented on an MR Linac system. Testing mechanics and their respective baselines may vary across institutions, but all necessary components for a post-software upgrade QA have been outlined and detailed. These outlined tests were demonstrated feasible for a low-field MR Linac system; however, the scope of this work may be applied and adapted more broadly to other online ART platforms., Competing Interests: The listed authors have received past funding from ViewRay Inc. Mittauer, Chuong, Kotecha, Bayouth, Mittauer, Bassiri. The listed authors have received honoraria in the past from ViewRay Inc. Chuong, Kotecha, Mittauer. The listed authors have had ownership stakes in past in companies that provided consulting services in image guided radiation therapy Mittauer, Bayouth. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bassiri, Bayouth, Chuong, Kotecha, Weiss, Mehta, Gutierrez and Mittauer.)

Purpose/objective: Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes., Materials/methods: Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin et al. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used., Results: From 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and proton therapy (19%). 61 patients had major CPTTB (score ≥ 70). Increasing CPTTB was predictive of decreased OS (p<0.001), lengthier post-esophagectomy length of stay (LOS, p<0.001), and death or readmission within 60 days of surgery (DR60, p<0.001). Major CPTTB was also predictive of decreased OS (hazard ratio = 1.70, 95% confidence interval: 1.17-2.47, p=0.005). The RPA-based risk score included: age ≥ 65, grade ≥ 2 nausea or esophagitis attributed to chemoradiation, and grade ≥ 3 hematologic toxicity attributed to chemoradiation. Patients treated with 3D radiotherapy had inferior OS (p=0.010) and increased major CPTTB (18.5% vs. 6.1%, p<0.001)., Conclusion: CPTTB predicts for OS, LOS, and DR60. Patients with 3D radiotherapy or age ≥ 65 years and chemoradiation toxicity are at highest risk for major CPTTB, predicting for higher short and long-term morbidity and mortality. Strategies to optimize medical management and reduce toxicity from chemoradiation should be strongly considered., Competing Interests: The spouse of RK is a senior technical product manager for GE Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kowalchuk, Spears, Morris, Owen, Yoon, Jethwa, Chuong, Ferris, Haddock, Hallemeier, Wigle, Lin and Merrell.)

Purpose/objectives: Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children., Materials/methods: All patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonance-guided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments., Results: Between 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a non-adaptive workflow. Two patients received fractionated MRgRT for an ALK-rearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments., Conclusions: In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing., Competing Interests: Author MH reports grants from the Florida Department of Health Live Like Bella Pediatric Cancer Research Initiative, personal fees from Ion Beam Associates (IBA), outside the submitted work. Author KM reports personal fees and nonfinancial support from ViewRay, other from MR Guidance, LLC, outside the submitted work. Author RK reports personal fees and non-financial support from Elekta, grants from Novocure, personal fees from Accuray, grants from Blue Earth Diagnostics, grants from Medtronic, grants from AstraZeneca, grants from Exelixis, personal fees from ViewRay, outside the submitted work. Author AG reports personal fees and non-financial support from ViewRay, outside the submitted work. Author MC reports grants, personal fees and non-financial support from ViewRay, personal fees from Sirtex, grants from Novocure, personal fees from Advanced Accelerator Applications, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hall, Mittauer, Herrera, Von Werne, Kotecha, Kalman, McCulloch, Alvarez, McAllister, Doty, Rzepczynski, Deere, Gutierrez and Chuong.)

Background: Radiation therapy (RT) dose for inoperable pancreatic ductal adenocarcinoma (PDAC) has historically been non-ablative to avoid injuring gastrointestinal (GI) organs at risk (OARs). Accruing data suggest that dose escalation, in select patients, may significantly improve clinical outcomes. Early results of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) have been encouraging, although long-term outcomes are not well understood., Methods: A single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction A-SMART on a 0.35T-MR Linac from 2018-2021., Results: Sixty-two patients were evaluated with a median age of 66 years (range 35-91) and nearly all achieved Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (96.8%). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%), or medically inoperable (4.8%). All received induction chemotherapy for a median 4.2 months (range, 0.2-13.3) most commonly FOLFIRINOX (n=43; 69.4%). Median prescribed dose was 50 Gy (range 40-50); median biologically effective dose (BED 10 ) was 100 Gy 10 . The median local control (LC), progression-free survival (PFS), and overall survival (OS) from diagnosis were not reached, 20 months, and 23 months, respectively. Also, 2-year LC, PFS, and OS were 68.8%, 40.0%, and 45.5%, respectively. Acute and late grade 3+ toxicity rates were 4.8% and 4.8%, respectively., Conclusions: To our knowledge, this is the largest series of induction chemotherapy followed by ablative 5-fraction SMART delivered on an MR Linac for inoperable PDAC. The potential for this novel treatment strategy is to achieve long-term LC and OS, compared to chemotherapy alone, and warrants prospective evaluation., Competing Interests: RK reports personal fees and non-financial support from Elekta, grants from Novocure, personal fees from Accuray, grants from Blue Earth Diagnostics, grants from Medtronic, grants from AstraZeneca, grants from Exelixis, personal fees from ViewRay, outside the submitted work. AG reports personal fees and non-financial support from ViewRay, outside the submitted work. DA reports grants from Sirtex, outside the submitted work. MC reports grants, personal fees and non-financial support from ViewRay, personal fees from Sirtex, grants from Novocure, personal fees from Advanced Accelerator Applications, outside the submitted work. KM reports personal fees and non-financial support from ViewRay, other from MR Guidance, LLC, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chuong, Herrera, Kaiser, Rubens, Romaguera, Alvarez, Kotecha, Hall, McCulloch, Ucar, DeZarraga, Aparo, Joseph, Asbun, Jimenez, Narayanan, Gutierrez and Mittauer.)

Radiation therapy (RT) is an integral component of potentially curative management of esophageal cancer (EC). However, RT can cause significant acute and late morbidity due to excess radiation exposure to nearby critical organs, especially the heart and lungs. Sparing these organs from both low and high radiation dose has been demonstrated to achieve clinically meaningful reductions in toxicity and may improve long-term survival. Accruing dosimetry and clinical evidence support the consideration of proton beam therapy (PBT) for the management of EC. There are critical treatment planning and delivery uncertainties that should be considered when treating EC with PBT, especially as there may be substantial motion-related interplay effects. The Particle Therapy Co-operative Group Thoracic and Gastrointestinal Subcommittees jointly developed guidelines regarding patient selection, treatment planning, clinical trials, and future directions of PBT for EC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chuong, Hallemeier, Li, Zhu, Zhang, Tryggestad, Yu, Yang, Choi, Kang, Liu, Knopf, Meijers, Molitoris, Apisarnthanarax, Giap, Hoppe, Lee, Chang, Simone and Lin.)

An international group of 22 liver cancer experts from 18 institutions met in Miami, Florida to discuss the optimal utilization of proton beam therapy (PBT) for primary and metastatic liver cancer. There was consensus that PBT may be preferred for liver cancer patients expected to have a suboptimal therapeutic ratio from XRT, but that PBT should not be preferred for all patients. Various clinical scenarios demonstrating appropriateness of PBT vs. XRT were reviewed.