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.

PD-1 inhibition combined with intensity-modulated radiotherapy, to better serve patients with retroperitoneal lymph node metastases from gastrointestinal cancer.

Background: Gastrointestinal (GI) cancer is the most frequent kind of cancer to involve the retroperitoneal lymph nodes (RPLNs). Radiotherapy (RT) is common treatment of RPLN metastases in patients with GI cancer, while RT is local. Meanwhile, most patients have extra-retroperitoneal metastases. Immunotherapy plus RT have showed effective in advanced non-small cell lung cancer. However, whether the combination therapy is effective on GI cancer with RPLN metastases. In our study, we would estimate the effect of programmed death-1 (PD-1) inhibition in association with intensity modulated radiation therapy (IMRT). Methods: Metastatic GI cancer patients with RPLN who were treated at a single institution were retrospectively evaluated from October 2016 to April 2023, who all had measurable lesion and received any therapy of PD-1 inhibitors alone, IMRT alone or PD-1 inhibitors plus IMRT. The follow-ups were assessed by abdominal computed tomography (CT) every 2 or 3 months to progression, dose-limiting toxicity or death. Results: Among the 98 patients, 46 were treated by PD-1 inhibitors combined with IMRT, 26 were by PD-1 inhibitors only and 26 were by IMRT only. Of those, the median age 62 years (range, 25-84 years). Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 10.8 months across the 3 therapy groups. Univariate analysis (UVA) indicated that therapy method (P=0.032) and tumor response (P=0.035) were significantly related to PFS. In the PD-1 inhibitors plus IMRT group, 1 patient (2.2%) achieved complete response (CR), 30 (65.2%) had partial remission, and 14 (30.4%) had stable disease. There was no case with CR by IMRT or PD-1 inhibitors alone. Objective response rate (67.4%) and disease control rate (97.8%) were higher in the PD-1 inhibitors combined with IMRT group. In the PD-1 inhibitors plus IMRT and PD-1 inhibitors alone groups, hepatitis B virus (HBV)-positive patients had better OS (P=0.041) on UVA. Meanwhile, in the PD-1 inhibitors plus IMRT group, we observed superior PFS (P=0.041) and OS (P=0.049) in HBV-positive patients on UVA. Conclusions: PD-1 inhibitors plus IMRT may be a better method for advanced GI cancer patients with RPLN metastases. HBV-positive patients can benefit from either PD-1 inhibitors alone or in combination with IMRT.

Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas.

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.

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.

Multi-institutional experience of MR-guided stereotactic body radiation therapy for adrenal gland metastases.

Purpose: While dose escalation is associated with improved local control (LC) for adrenal gland metastases (AGMs), the proximity of gastrointestinal (GI) organs-at-risk (OARs) limits the dose that can be safely prescribed via CT-based stereotactic body radiation therapy (SBRT). The advantages of magnetic resonance-guided SBRT (MRgSBRT), including tumor tracking and online plan adaptation, facilitate safe dose escalation. Methods: This is a multi-institutional review of 57 consecutive patients who received MRgSBRT on a 0.35-T MR linac to 61 AGMs from 2019 to 2021. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and LC, and the Cox proportional hazards model was utilized for univariate analysis (UVA). Results: Median follow up from MRgSBRT was 16.4 months (range [R]: 1.1-39 months). Median age was 67 years (R: 28-84 years). Primary histologies included non-small cell lung cancer (N = 38), renal cell carcinoma (N = 6), and melanoma (N = 5), amongst others. The median maximum diameter was 2.7 cm (R: 0.6-7.6 cm), and most AGMs were left-sided (N = 32). The median dose was 50 Gy (R: 30-60 Gy) in 5-10 fractions with a median BED10 of 100 Gy (R: 48-132 Gy). 45 cases (74 %) required adaptation for at least 1 fraction (median: 4 fractions, R: 0-10). Left-sided AGMs required adaptation in at least 1 fraction more frequently than right-sided AGMs (88 % vs 59 %, p = 0.018). There were 3 cases of reirradiation, including 60 Gy in 10 fractions (N = 1) and 40 Gy in 5 fractions (N = 2). One-year LC, PFS, and OS were 92 %, 52 %, and 78 %, respectively. On UVA, melanoma histology predicted for inferior 1-year LC (80 % vs 93 %, p = 0.012). There were no instances of grade 3+ toxicity. Conclusions: We demonstrate that MRgSBRT achieves favorable early LC and no grade 3 + toxicity despite prescribing a median BED10 of 100 Gy to targets near GI OARs.

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.

AAPM Medical Physics Practice Guideline 14.a: Yttrium-90 microsphere radioembolization.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

MRI-Guided Adaptive Radiation Therapy.

Magnetic resonance imaging-guided radiation therapy (MRIgRT) has improved soft tissue contrast over computed tomography (CT) based image-guided RT. Superior visualization of the target and surrounding radiosensitive structures has the potential to improve oncological outcomes partly due to safer dose-escalation and adaptive planning. In this review, we highlight the workflow of adaptive MRIgRT planning, which includes simulation imaging, daily MRI, identifying isocenter shifts, contouring, plan optimization, quality control, and delivery. Increased utilization of MRIgRT will depend on addressing technical limitations of this technology, while addressing treatment efficacy, cost-effectiveness, and workflow training.

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.

Ablative 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy for Oligometastatic Pancreatic Adenocarcinoma.

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.

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.

Proton Beam Therapy and Photon-Based Magnetic Resonance Image-Guided Radiation Therapy: The Next Frontiers of Radiation Therapy for Hepatocellular Carcinoma.

External beam radiation therapy (EBRT) has increasingly been utilized in the treatment of hepatocellular carcinoma (HCC) due to technological advances with positive clinical outcomes. Innovations in EBRT include improved image guidance, motion management, treatment planning, and highly conformal techniques such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT). Moreover, proton beam therapy (PBT) and magnetic resonance image-guided radiation therapy (MRgRT) have expanded the capabilities of EBRT. PBT offers the advantage of minimizing low- and moderate-dose radiation to the surrounding normal tissue, thereby preserving uninvolved liver and allowing for dose escalation. MRgRT provides the advantage of improved soft tissue delineation compared to computerized tomography (CT) guidance. Additionally, MRgRT with online adaptive therapy is particularly useful for addressing motion not otherwise managed and reducing high-dose radiation to the normal tissue such as the stomach and bowel. PBT and online adaptive MRgRT are emerging technological advancements in EBRT that may provide a significant clinical benefit for patients with HCC.

Tumor treating fields: narrative review of a promising treatment modality for cancer.

BACKGROUND AND OBJECTIVE: Tumor treating fields (TTFields) therapy have emerged as a potentially effective treatment for various malignancies by delivering low-intensity, intermediate-frequency electrical fields that disrupt many processes inside cells, resulting in the interruption of cell division in cancer cells. Additionally, TTFields therapy has been found to be synergistic with existing therapeutic approaches. In this review, we provide an introduction and background to the primary mechanisms of TTFields and discuss the emerging preclinical and clinical outcomes of this novel cancer treatment technology. METHODS: We performed a literature search on PubMed, ClinicalTrials.Gov, and Google Scholar using the terms 'TTFields' and 'cancer'. We included studies, review articles, and editorials published in English from 1st January 2000 to 1st October 2023. All obtained publications were reviewed and their key references are cross-checked to ensure a balanced and high-quality review. KEY CONTENT AND FINDINGS: Clinical studies reported to date have demonstrated the survival advantage of TTFields therapy in newly diagnosed glioblastoma (GBM), non-small cell lung cancer (NSCLC), and meaningful clinical activity in recurrent GBM (rGBM) and malignant pleural mesothelioma. Moreover, TTFields therapy has exhibited promising safety profiles across a diverse range of cancers including pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, NSCLC, and gastric cancer, when combined with cytotoxic chemotherapy and/or immunotherapy regimens, suggesting broad applicability as an added treatment modality. CONCLUSIONS: Based on preclinical and clinical studies, TTFields therapy show promise as a potential treatment option for patients with a number of different malignancies, offering a favorable safety profile and the potential for significant clinical benefit. Further research is warranted to establish the optimal treatment parameters and identify specific patient subgroups that may derive the greatest advantage from this treatment modality.

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.

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.

Neoadjuvant chemotherapy and stereotactic body radiation therapy for borderline resectable pancreas adenocarcinoma: influence of vascular margin status and type of chemotherapy.

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.