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Single-fraction stereotactic radiosurgery (SRS) or fractionated SRS (FSRS) are well established strategies for patients with limited brain metastases. A broad spectrum of modern dedicated platforms are currently available for delivering intracranial SRS/FSRS; however, SRS/FSRS delivered using traditional CT-based platforms relies on the need for diagnostic MR images to be coregistered to planning CT scans for target volume delineation. Additionally, the on-board image guidance on traditional platforms yields limited inter-fraction and intra-fraction real-time visualization of the tumor at the time of treatment delivery. MR Linacs are capable of obtaining treatment planning MR and on-table MR sequences to enable visualization of the targets and organs-at-risk and may subsequently help identify anatomical changes prior to treatment that may invoke the need for on table treatment adaptation. Recently, an MR-guided intracranial package (MRIdian A3i BrainTx TM ) was released for intracranial treatment with the ability to perform high-resolution MR sequences using a dedicated brain coil and cranial immobilization system. The objective of this report is to provide, through the experience of our first patient treated, a comprehensive overview of the clinical application of our institutional program for FSRS adaptive delivery using MRIdian's A3i BrainTx system-highlights include reviewing the imaging sequence selection, workflow demonstration, and details in its delivery feasibility in clinical practice, and dosimetric outcomes., Competing Interests: Conflict of Interest All remaining authors declare no conflicts of interest., (Copyright © 2024 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered., Methods and Materials: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, or 3) based on adequacy. A score of 1 indicated no deviation, 2 indicated minor deviation, and 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score., Results: Forty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic and 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets and 4 for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT and 7 (17.9%) with hypofractionated RT. Five cases (13%) required revision before treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2, and 11 (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded., Conclusions: Despite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. Although clinical outcomes did not appear to have been affected, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This is the first reporting of the MRIdian A3i TM intracranial package (BrainTx TM ) and benchmarks the end-to-end localization and dosimetric accuracy for commissioning an magnetic resonace (MR)-guided stereotactic radiosurgery program. We characterized the localization accuracy between MR and radiation (RT) isocenter through an end-to-end hidden target test, relative dose profile intercomparison, and absolute dose validation., Methods and Materials: BrainTx consists of a dedicated head coil, integrated mask immobilization system, and high-resolution MR sequences. Coil and baseplate attenuation was quantified. An in-house phantom (Cranial phantOm foR magNetic rEsonance Localization of a stereotactIc radiosUrgery doSimeter, CORNELIUS) was developed from a mannequin head filled with silicone gel, film, and MR BB with pinprick. A hidden target test evaluated MR-RT localization of the 1×1×1 mm 3 TrueFISP MR and relative dose accuracy in film for a 1 cm diameter (International Electrotechnical Commission (IEC)-X/IEC-Y) and 1.5 cm diameter (IEC-Y/IEC-Z) spherical target. Two clinical cases (irregular-shaped target and target abutting brainstem) were mapped to the CORNELIUS phantom for feasibility assessment. A 2-dimensional (2D)-gamma compared calculated and measured dose for spherical and clinical targets with 1 mm/1% and 2 mm/2% criteria, respectively. A small-field chamber (A26MR) measured end-to-end absolute dose for a 1 cm diameter target., Results: Coil and baseplate attenuation were 0.7% and 2.7%, respectively. The displacement of MR to RT localization as defined through the pinprick was 0.49 mm (IEC-X), 0.27 mm (IEC-Y), and 0.51 mm (IEC-Z) (root mean square 0.76 mm). The reproducibility across IEC-Y demonstrated high fidelity (<0.02 mm). Gamma pass rates were 97.1% and 95.4% for 1 cm and 1.5 cm targets, respectively. Dose profiles for an irregular-shaped target and abutting organ-at-risk-target demonstrated pass rates of 99.0% and 92.9%, respectively. The absolute end-to-end dose difference was <1%., Conclusions: All localization and dosimetric evaluation demonstrated submillimeter accuracy, per the TG-142, TG-101, MPPG 9.a. criteria for SRS/SRT systems, indicating acceptable delivery capabilities with a 1 mm setup margin., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity., Materials and Methods: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose 10 [BED 10 ] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART., Results: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively., Conclusions: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC)., Methods and Materials: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART., Results: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%., Conclusions: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The influence of chemotherapy type and vascular margin status after sequential chemotherapy and stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic cancer (BRPC) is unknown., Methods: A retrospective review was performed on BRPC patients treated with chemotherapy and 5-fraction SBRT from 2009 to 2021. Surgical outcomes and SBRT-related toxicity were reported. Clinical outcomes were estimated by Kaplan-Meier with log rank comparisons., Results: A total of 303 patients received neoadjuvant chemotherapy and SBRT to a median dose of 40 Gy prescribed to the tumor-vessel interface and median dose of 32.4 Gyto 95% of the gross tumor volume. One hundred and sixty-nine patients (56%) were resected and benefited from improved median OS (41.1 vs 15.5 months, P < 0.001). Close/positive vascular margins were not associated with worse OS or FFLRF. Type of neoadjuvant chemotherapy did not influence OS for resected patients, but FOLFIRINOX was associated with improved median OS in unresected patients (18.2 vs 13.1 months, P = 0.001)., Conclusion: For BRPC, the effect of a positive or close vascular margin may be mitigated by neoadjuvant therapy. Shorter duration neoadjuvant chemotherapy as well as the optimal biological effective dose of radiotherapy should be prospectively explored., Competing Interests: Conflict of interest None to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood., Methods: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5)., Results: A total of 49 patients were evaluated with a median age of 81 years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50 Gy (range, 40-50 Gy) in 5 fractions. 1 Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6 months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively., Conclusions: A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

Introduction: Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease., Methods: We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy., Results: From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1-6 metastases) received SMART to the primary tumor with a median follow-up of 11.2 months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50 Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9 months and 11.6 months, respectively. Calculated from SMART, the median PFS was 2.4 months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity., Conclusion: There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: November 2022 and January 2023, travel expenses were partially supported by View Ray. October 2022, meal expense support from Galera Therapeutics.

Given the positive results from recent randomized controlled trials in patients with oligometastatic, oligoprogressive, or oligoresidual disease, the role of radiotherapy has expanded in patients with metastatic non-small cell lung cancer (NSCLC). While small metastatic lesions are commonly treated with stereotactic body radiotherapy (SBRT), treatment of the primary tumor and involved regional lymph nodes may require prolonged fractionation schedules to ensure safety especially when treating larger volumes in proximity to critical organs-at-risk (OARs). We have developed an institutional MR-guided adaptive radiotherapy (MRgRT) workflow for these patients. We present a 71-year-old patient with stage IV NSCLC with oligoprogression of the primary tumor and associated regional lymph nodes in which MR-guided, online adaptive radiotherapy was performed, prescribing 60 Gy in 15 fractions. We describe our workflow, dosimetric constraints, and daily dosimetric comparisons for the critical OARs (esophagus, trachea, and proximal bronchial tree [PBT] maximum doses [D 0.03cc ]), in comparison to the original treatment plan recalculated on the anatomy of the day (i.e., predicted doses). During MRgRT, few fractions met the original dosimetric objectives: 6.6% for esophagus, 6.6% for PBT, and 6.6% for trachea. Online adaptive radiotherapy reduced the cumulative doses to the structures by 11.34%, 4.2%, and 5.62% when comparing predicted plan summations to the final delivered summation. Therefore, this case study presets a workflow and treatment paradigm for accelerated hypofractionated MRgRT due to the significant variations in daily dose to the central thoracic OARs to reduce treatment-related toxicity associated with radiotherapy., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: To quantify the indication for adaptive, gated breath-hold (BH) MR-guided radiotherapy (MRgRT BH ) versus BH or free-breathing (FB) CT-based image-guided radiotherapy (CT-IGRT) for the ablative treatment of adrenal malignancies., Materials and Methods: Twenty adrenal patients underwent adaptive IMRT MRgRT BH to a median dose of 50 Gy/5 fractions. Each patient was replanned for VMAT CT-IGRT BH and CT-IGRT FB on a c-arm linac. Only CT-IGRT FB used an ITV, summed from GTVs of all phases of the 4DCT respiratory evaluation. All used the same 5 mm GTV/ITV to PTV expansion. Metrics evaluated included: target volume and coverage, conformality, mean ipsilateral kidney and 0.5 cc gastrointestinal organ-at-risk (OAR) doses (D 0.5cc ). Adaptive dose for MRgRT BH and predicted dose (i.e., initial plan re-calculated on anatomy of the day) was performed for CT-IGRT BH and MRgRT BH to assess frequency of OAR violations and coverage reductions for each fraction., Results: The more common VMAT CT-IGRT FB , with its significantly larger target volumes, proved inferior to MRgRT BH in mean PTV and ITV/GTV coverage, as well as small bowel D 0.5cc . Conversely, VMAT CT-IGRT BH delivered a dosimetrically superior initial plan in terms of statistically significant (p ≤ 0.02) improvements in target coverage, conformality and D 0.5cc to the large bowel, duodenum and mean ipsilateral kidney compared to IMRT MRgRT BH . However, non-adaptive CT-IGRT BH had a 71.8% frequency of predicted indications for adaptation and was 2.8 times more likely to experience a coverage reduction in PTV D 95% than predicted for MRgRT BH ., Conclusion: Breath-hold VMAT radiotherapy provides superior target coverage and conformality over MRgRT BH , but the ability of MRgRT BH to safely provide ablative doses to adrenal lesions near mobile luminal OAR through adaptation and direct, real-time motion tracking is unmatched., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Although peer review in radiation oncology (RO) has been recommended to improve quality of care, an analysis of modifications resulting from an RO multidisciplinary presimulation standardized review process has yet to be empirically demonstrated., Methods and Materials: A standardized simulation directive was used for patients undergoing simulation for external beam radiation therapy at a single tertiary care institution. The simulation directives were presented, and all aspects were reviewed by representatives from key RO disciplines. Modifications to the original directives were prospectively captured in a quality improvement registry. Association between key variables and the incidence of modifications were performed using Fisher exact test and t test., Results: A registry of 500 consecutive simulations for patients undergoing radiation therapy was reviewed. A median of 105 simulations occurred per month. All simulation directives were entered by a physician a median of 3 days before simulation (range, 1-76 days). The treatment intent was curative for 269 patients (53.8%), palliative for 203 patients (40.6%), and benign for 3 patients (0.6%). Twenty-five (5%) patients did not have a treatment intent selected. Based on RO multidisciplinary review, 105 directives (21%) were modified from the original intent, with 29 (5.8%) requiring more than 1 modification. A total of 149 modifications were made and categorized as changes to patient positioning and immobilization (n = 100, 20%), treatment site and care path (n = 34, 6.8%), simulation coordination activities (n = 6, 1.2%), and treatment technique and planning instructions (n = 9, 1.8%). A higher proportion of modifications occurred at the time of multidisciplinary review in patients receiving more complex treatments (intensity modulated radiation therapy/stereotactic radiosurgery/stereotactic body radiation therapy [IMRT/SRS/SBRT] vs 3-dimensional radiation therapy [3DCRT] radiation therapy, 25% vs 16%, P < .025)., Conclusions: Given the complexity of radiation therapy simulation, standardization of directives with prospective RO multidisciplinary presimulation peer review is critical to optimizing department processes and reducing errors. Approximately 1 in 5 patients benefits from this peer review process, especially patients treated with IMRT/SRS/SBRT., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Radiation therapy dose escalation using stereotactic body radiation therapy may significantly improve both local control (LC) and overall survival (OS) for patients with inoperable pancreas cancer. However, ablative dose cannot be routinely offered because of the risk of causing severe injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents a novel technique that may achieve safe delivery of ablative dose and improve long-term outcomes., Methods and Materials: We performed a single institution retrospective analysis of 35 consecutive pancreatic cancer patients treated with SMART in mid-inspiration breath hold on an MR-linear accelerator. Most had locally advanced disease (80%) and received induction chemotherapy (91.4%) for a median 3.9 months before stereotactic body radiation therapy. All were prescribed 5 fractions delivered in consecutive days to a median total dose of 50 Gy (BED 10 100 Gy 10 ), typically with a 120% to 130% hotspot. Elective nodal irradiation was delivered to 20 (57.1%) patients. No patient had fiducial markers placed and all were treated with continuous intrafraction MR visualization and automatic beam triggering., Results: With median follow-up of 10.3 months from SMART, acute (2.9%) and late (2.9%) grade 3 toxicities were uncommon. One-year LC, distant metastasis-free survival, progression-free survival, cause-specific survival, and OS were 87.8%, 63.1%, 52.4%, 77.6%, and 58.9%, respectively., Conclusions: To our knowledge, this is the first report of 5-fraction pancreas SMART delivered on an MR-linear accelerator. We observed minimal severe treatment-related toxicity and encouraging early LC. Prospective confirmation of feasibility and long-term clinical outcomes of dose intensified SMART is warranted., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity., Methods and Materials: A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered for resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS)., Results: Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%)., Conclusions: SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer., (Copyright © 2013. Published by Elsevier Inc.)