Case report: Intrafraction dose-guided tracking for gastrointestinal organ-at-risk isotoxicity delivery on an MR-guided radiotherapy system.

In the current era of high-precision radiation therapy, real-time magnetic resonance (MR)-guided tracking of the tumor and organs at risk (OARs) is a novel approach that enables accurate and safe delivery of high-dose radiation. Organ tracking provides a general sense of the need for daily online adaptation but lacks precise information regarding exact dosimetry. To overcome this limitation, we developed the methodology for monitoring intrafraction motion with real-time MR-guided isodose line-based tracking of an OAR in combination with anatomic tumor-based tracking and reported the first case treated with this approach. An isolated para-aortic (PA) nodal recurrence from carcinosarcoma of the endometrium was treated with an ablative dose of 50 Gy in five fractions using MR-guided radiotherapy (MRgRT). This report demonstrates the feasibility, workflow, dosimetric constraints, and treatment paradigm for real-time isodose line-based OAR tracking and gating to enable an isotoxicity delivery approach. This innovative treatment strategy effectively tracked the intrafraction motion of both the target and OAR independently and enhanced the accuracy of structure localization in time and space with a more precise dosimetric evaluation.

Quality assurance of an established online adaptive radiotherapy program: patch and software upgrade.

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.

Clinical application of an institutional fractionated stereotactic radiosurgery (FSRS) program for brain metastases delivered with MRIdianⓇ BrainTx™.

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 BrainTxTM) 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.

Accelerated Hypofractionated Magnetic Resonance Guided Adaptive Radiation Therapy for Ultracentral Lung Tumors.

Radiotherapy for ultracentral lung tumors represents a treatment challenge, considering the high rates of high-grade treatment-related toxicities with stereotactic body radiation therapy (SBRT) or hypofractionated schedules. Accelerated hypofractionated magnetic resonance-guided adaptive radiation therapy (MRgART) emerged as a potential game-changer for tumors in these challenging locations, in close proximity to central organs at risk, such as the trachea, proximal bronchial tree, and esophagus. In this series, 13 consecutive patients, predominantly male (n = 9), with a median age of 71 (range (R): 46-85), underwent 195 MRgART fractions (all 60 Gy in 15 fractions) to metastatic (n = 12) or primary ultra-central lung tumors (n = 1). The median gross tumor volumes (GTVs) and planning target volumes (PTVs) were 20.72 cc (R: 0.54-121.65 cc) and 61.53 cc (R: 3.87-211.81 cc), respectively. The median beam-on time per fraction was 14 min. Adapted treatment plans were generated for all fractions, and indications included GTV/PTV undercoverage, OARs exceeding tolerance doses, or both indications in 46%, 18%, and 36% of fractions, respectively. Eight patients received concurrent systemic therapies, including immunotherapy (four), chemotherapy (two), and targeted therapy (two). The crude in-field loco-regional control rate was 92.3%. No CTCAE grade 3+ toxicities were observed. Our results offer promising insights, suggesting that MRgART has the potential to mitigate toxicities, enhance treatment precision, and improve overall patient care in the context of ultracentral lung tumors.

Commissioning Intracranial Stereotactic Radiosurgery for a Magnetic Resonance-Guided Radiation Therapy (MRgRT) System: MR-RT Localization and Dosimetric End-to-End Validation.

PURPOSE: This is the first reporting of the MRIdian A3iTM intracranial package (BrainTxTM) 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 mm3 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.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study.

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 dose10 [BED10] = 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.

Dosimetric comparison of magnetic resonance-guided radiation therapy, intensity-modulated proton therapy and volumetric-modulated arc therapy for distal esophageal cancer.

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

A multi-centric evaluation of self-learning GAN based pseudo-CT generation software for low field pelvic magnetic resonance imaging.

Purpose/objectives: An artificial intelligence-based pseudo-CT from low-field MR images is proposed and clinically evaluated to unlock the full potential of MRI-guided adaptive radiotherapy for pelvic cancer care. Materials and method: In collaboration with TheraPanacea (TheraPanacea, Paris, France) a pseudo-CT AI-model was generated using end-to-end ensembled self-supervised GANs endowed with cycle consistency using data from 350 pairs of weakly aligned data of pelvis planning CTs and TrueFisp-(0.35T)MRIs. The image accuracy of the generated pCT were evaluated using a retrospective cohort involving 20 test cases coming from eight different institutions (US: 2, EU: 5, AS: 1) and different CT vendors. Reconstruction performance was assessed using the organs at risk used for treatment. Concerning the dosimetric evaluation, twenty-nine prostate cancer patients treated on the low field MR-Linac (ViewRay) at Montpellier Cancer Institute were selected. Planning CTs were non-rigidly registered to the MRIs for each patient. Treatment plans were optimized on the planning CT with a clinical TPS fulfilling all clinical criteria and recalculated on the warped CT (wCT) and the pCT. Three different algorithms were used: AAA, AcurosXB and MonteCarlo. Dose distributions were compared using the global gamma passing rates and dose metrics. Results: The observed average scaled (between maximum and minimum HU values of the CT) difference between the pCT and the planning CT was 33.20 with significant discrepancies across organs. Femoral heads were the most reliably reconstructed (4.51 and 4.77) while anal canal and rectum were the less precise ones (63.08 and 53.13). Mean gamma passing rates for 1%1mm, 2%/2mm, and 3%/3mm tolerance criteria and 10% threshold were greater than 96%, 99% and 99%, respectively, regardless the algorithm used. Dose metrics analysis showed a good agreement between the pCT and the wCT. The mean relative difference were within 1% for the target volumes (CTV and PTV) and 2% for the OARs. Conclusion: This study demonstrated the feasibility of generating clinically acceptable an artificial intelligence-based pseudo CT for low field MR in pelvis with consistent image accuracy and dosimetric results.

Online adaptive radiotherapy: Assessment of planning technique and its impact on longitudinal plan quality robustness in pancreatic cancer.

BACKGROUND AND PURPOSE: Planning on a static dataset that reflects the simulation day anatomy is routine for SBRT. We hypothesize the quality of on-table adaptive plans is similar to the baseline plan when delivering stereotactic MR-guided adaptive radiotherapy (SMART) for pancreatic cancer (PCa). MATERIALS AND METHODS: Sixty-seven inoperable PCa patients were prescribed 50 Gy/5-fraction SMART. Baseline planning included: 3-5 mm gastrointestinal (GI) PRV, 50 Gy optimization target (PTVopt) based on GI PRV, conformality rings, and contracted GTV to guide the hotspot. For each adaptation, GI anatomy was re-contoured, followed by re-optimization. Plan quality was evaluated for target coverage (TC = PTVopt V100%/volume), PTV D90% and D80%, homogeneity index (HI = PTVopt D2%/D98%), prescription isodose/target volume (PITV), low-dose conformity (D2cm = maximum dose at 2 cm from PTVopt/Rx dose), and gradient index (R50%=50% Rx isodose volume/PTVopt volume).A novel global planning metric, termed the Pancreas Adaptive Radiotherapy Score (PARTS), was developed and implemented based on GI OAR sparing, PTV/GTV coverage, and conformality. Adaptive robustness (baseline to fraction 1) and stability (difference between two fractions with highest GI PRV variation) were quantified. RESULTS: OAR constraints were met on all baseline (n = 67) and adaptive (n = 318) plans. Coverage for baseline/adaptive plans was mean ± SD at 44.9 ± 5.8 Gy/44.3 ± 5.5 Gy (PTV D80%), 50.1 ± 4.2 Gy/49.1 ± 4.7 Gy (PTVopt D80%), and 80%±18%/74%±18% (TC), respectively. Mean homogeneity and conformality for baseline/adaptive plans were 0.87 ± 0.25/0.81 ± 0.30 (PITV), 3.81 ± 1.87/3.87 ± 2.0 (R50%), 1.53 ± 0.23/1.55 ± 0.23 (HI), and 58%±7%/59%±7% (D2cm), respectively. PARTS was found to be a sensitive metric due to its additive influence of geometry changes on PARTS' sub-metrics. There were no statistical differences (p > 0.05) for stability, except for PARTS (p = 0.04, median difference -0.6%). Statistical differences for robustness when significant were small for most metrics (<2.0% median). Median adaptive re-optimizations were 2. CONCLUSION: We describe a 5-fraction ablative SMART planning approach for PCa that is robust and stable during on-table adaption, due to gradients controlled by a GI PRV technique and the use of rings. These findings are noteworthy given that daily interfraction anatomic GI OAR differences are routine, thus necessitating on-table adaptation. This work supports feasibility towards utilizing a patient-independent, template on-table adaptive approach.

Characterization of mechanical and radiation isocenter on an MR-guided radiotherapy (MRgRT) Linac.

BACKGROUND AND PURPOSE: In the emerging paradigm of stereotactic radiosurgery being proposed for MR-guided radiotherapy (MRgRT), assessment of mechanical geometric accuracy is critical for the implementation of stereotactic delivery. We benchmarked the mechanical accuracy of an MR Linac system that lacks an onboard detector/array. Our mechanical tests utilize a half beam block (HBB) geometry that takes advantage of the sensitivity of a partially occluded detector. MATERIALS AND METHODS: Mechanical tests benchmarked the couch, MLC, and gantry geometric accuracy for an MR-Linac system. An HBB technique was used to irradiate an ionization chamber profiler (ICP) array with partial occlusion of individual detectors for characterization of MLC skew, beam divergence displacement, and RT isocenter localization. The sensitivity of the partially occluded detector's ICP-X (detector width) and ICP-Y (detector length) was characterized by displacing the detector relative to radiation isocenter by 0.2 mm increments, introduced through couch motion. The accuracy of the HBB ICP technique was verified with a starshot using radiochromic film, and the reproducibility was verified on a conventional C-arm Linac and compared to Winston-Lutz. RESULTS: The sensitivity of the HBB technique as quantified through the dose difference normalized to open field as a function of displacement from RT isocenter was 6.4%/mm and 13.0%/mm for the ICP-X and ICP-Y orientation, respectively, due to the oblong detector orientation. Couch positional accuracy and sag was within ±0.1 mm. Maximum MLC positional displacement was 0.7 mm with mean MLC skew at 0.07°. The maximum beam divergence displacement was 0.03 mm. The gantry angle was within 0.1°. Independent verification of the RT isocenter localization procedure produced repeatable results. CONCLUSION: This work serves for characterizing the mechanical and geometric radiation accuracy for the foundation of an MR-guided stereotactic radiosurgery program, as demonstrated with high sensitivity and independent validation.

Accelerated hypofractionated magnetic resonance-guided adaptive radiotherapy for oligoprogressive non-small cell lung cancer.

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 [D0.03cc]), 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.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

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.

Treatment of glioblastoma using MRIdian® A3i BrainTx™: Imaging and treatment workflow demonstration.

For patients with newly diagnosed glioblastoma, the current standard-of-care includes maximal safe resection, followed by concurrent chemoradiotherapy and adjuvant temozolomide, with tumor treating fields. Traditionally, diagnostic imaging is performed pre- and post-resection, without additional dedicated longitudinal imaging to evaluate tumor volumes or other treatment-related changes. However, the recent introduction of MR-guided radiotherapy using the ViewRay MRIdian A3i system includes a dedicated BrainTx package to facilitate the treatment of intracranial tumors and provides daily MR images. We present the first reported case of a glioblastoma imaged and treated using this workflow. In this case, a 67-year-old woman underwent adjuvant chemoradiotherapy after gross total resection of a left frontal glioblastoma. The radiotherapy treatment plan consisted of a traditional two-phase design (46 Gy followed by a sequential boost to a total dose of 60 Gy at 2 Gy/fraction). The treatment planning process, institutional workflow, treatment imaging, treatment timelines, and target volume changes visualized during treatment are presented. This case example using our institutional A3i system workflow successfully allows for imaging and treatment of primary brain tumors and has the potential for margin reduction, detection of early disease progression, or to detect the need for dose adaptation due to interfraction tumor volume changes.

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy.

Purpose: Nearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival. Methods and Materials: A single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART. Results: A total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy10. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs. Conclusions: To our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.

Considering Lumpectomy Cavity PTV Expansions: Characterization of Intrafraction Lumpectomy Cavity Motion.

PURPOSE: Accelerated partial breast irradiation and lumpectomy cavity boost radiation therapy plans generally use volumetric expansions from the lumpectomy cavity clinical target volume to the planning target volume (PTV) of 1 to 1.5 cm, substantially increasing the volume of irradiated breast tissue. The purpose of this study was to quantify intrafraction lumpectomy cavity motion during external beam radiation therapy to inform the indicated clinical target volume to PTV expansion. METHODS AND MATERIALS: Forty-four patients were treated with a whole breast irradiation using traditional linear accelerator-based radiation therapy followed by lumpectomy cavity boost using magnetic resonance (MR)-guided radiation therapy on a prospective registry study. Two-dimensional cine-MR images through the center of the surgical cavity were acquired during each boost treatment to define the treatment position of the lumpectomy cavity. This was compared with the reference position to quantify intrafraction cavity motion. Free-breathing technique was used during treatment. Clinical outcomes including toxicity, cosmesis, and rates of local control were additionally analyzed. RESULTS: The mean maximum displacement per fraction in the anterior-posterior (AP) direction was 1.4 mm. Per frame, AP motion was <5 mm in 92% of frames. The mean maximum displacement per fraction in the superior-inferior (SI) direction was 1.2 mm. Per frame, SI motion was <5 mm in 94% of frames. Composite motion was <5 mm in 89% of frames. Three-year local control was 97%. Eight women (18%) developed acute G2 radiation dermatitis. With a median follow-up of 32.4 months, cosmetic outcomes were excellent (22/44, 50%), good (19/44, 43%), and fair (2/44, 5%). CONCLUSIONS: In approximately 90% of analyzed frames, intrafraction displacement of the lumpectomy cavity was <5 mm, with even less motion expected with deep inspiratory breath hold. Our results suggest reduced PTV expansions of 5 mm would be sufficient to account for lumpectomy cavity position, which may accordingly reduce late toxicity and improve cosmetic outcomes.

Induction Chemotherapy and Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy for Inoperable Pancreas Cancer.

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 (BED10) was 100 Gy10. 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.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy10 for Non-bone Oligometastases.

Purpose: Randomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and Materials: The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. Results: Ninety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. Conclusions: To our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

Dose-Escalated Magnetic Resonance Image-Guided Abdominopelvic Reirradiation With Continuous Intrafraction Visualization, Soft Tissue Tracking, and Automatic Beam Gating.

PURPOSE: Compared with computed tomography, magnetic resonance (MR) image guidance offers significant advantages for radiation therapy (RT) that may be particularly beneficial for reirradiation (reRT). However, clinical outcomes of MR-guided reRT are not well described in the published literature. METHODS AND MATERIALS: We performed a single-institution retrospective safety and efficacy analysis of reRT patients treated on the MRIdian Linac to targets within the abdomen or pelvis using continuous intrafraction MR-based motion management with automatic beam triggering. Fiducial markers were not used. RESULTS: We evaluated 11 patients who received prior RT to a median of 50 Gy (range, 30-58.8 Gy) in 25 fractions (range, 5-28 fractions). The median interval to reRT was 26.8 months. The most frequently retreated sites were nodal metastases (36.4%) and pancreatic cancer (27.3%). The median reRT dose was 40 Gy (range, 25-54 Gy) in 6 fractions (range, 5-36 fractions); ultrahypofractionation (63.6%) was more common than hyperfractionation (36.4%). Daily on-table adaptive replanning was used for 3 patients (27.3%). With a median of 14 months' follow-up from reRT completion (range, 6-32 months), the median and 1-year freedom from local progression were 29 months and 88.9%, respectively, and the median and 1-year overall survival were 17.5 months and 70.0%, respectively. One patient (9.1%) experienced acute grade 2 toxic effects; there were no acute or late treatment-related toxic effects of grade 3 or greater. CONCLUSIONS: Magnetic resonance-guided reRT appeared to be feasible and may facilitate safe dose escalation. Additional follow-up is needed to better assess long-term efficacy and late toxic effects. Prospective evaluation of this novel treatment strategy is warranted.

CT-guided versus MR-guided radiotherapy: Impact on gastrointestinal sparing in adrenal stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To quantify the indication for adaptive, gated breath-hold (BH) MR-guided radiotherapy (MRgRTBH) 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 MRgRTBH to a median dose of 50 Gy/5 fractions. Each patient was replanned for VMAT CT-IGRTBH and CT-IGRTFB on a c-arm linac. Only CT-IGRTFB 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 (D0.5cc). Adaptive dose for MRgRTBH and predicted dose (i.e., initial plan re-calculated on anatomy of the day) was performed for CT-IGRTBH and MRgRTBH to assess frequency of OAR violations and coverage reductions for each fraction. RESULTS: The more common VMAT CT-IGRTFB, with its significantly larger target volumes, proved inferior to MRgRTBH in mean PTV and ITV/GTV coverage, as well as small bowel D0.5cc. Conversely, VMAT CT-IGRTBH delivered a dosimetrically superior initial plan in terms of statistically significant (p ≤ 0.02) improvements in target coverage, conformality and D0.5cc to the large bowel, duodenum and mean ipsilateral kidney compared to IMRT MRgRTBH. However, non-adaptive CT-IGRTBH had a 71.8% frequency of predicted indications for adaptation and was 2.8 times more likely to experience a coverage reduction in PTV D95% than predicted for MRgRTBH. CONCLUSION: Breath-hold VMAT radiotherapy provides superior target coverage and conformality over MRgRTBH, but the ability of MRgRTBH to safely provide ablative doses to adrenal lesions near mobile luminal OAR through adaptation and direct, real-time motion tracking is unmatched.