Artificial intelligence applications in prostate cancer.

Artificial intelligence (AI) applications have enabled remarkable advancements in healthcare delivery. These AI tools are often aimed to improve accuracy and efficiency of histopathology assessment and diagnostic imaging interpretation, risk stratification (i.e., prognostication), and prediction of therapeutic benefit for personalized treatment recommendations. To date, multiple AI algorithms have been explored for prostate cancer to address automation of clinical workflow, integration of data from multiple domains in the decision-making process, and the generation of diagnostic, prognostic, and predictive biomarkers. While many studies remain within the pre-clinical space or lack validation, the last few years have witnessed the emergence of robust AI-based biomarkers validated on thousands of patients, and the prospective deployment of clinically-integrated workflows for automated radiation therapy design. To advance the field forward, multi-institutional and multi-disciplinary collaborations are needed in order to prospectively implement interoperable and accountable AI technology routinely in clinic.

Development of an abdominal dose accumulation tool and assessments of accumulated dose in gastrointestinal organs.

Objective.Online adaptive radiotherapy has demonstrated improved dose conformality in response to inter-fraction geometric variations in the abdomen. The dosimetric impact of intra-fractional variations in anatomic configuration resulting from breathing, gastric contraction and slow configuration motion, however, have been largely ignored, leading to differences between delivered and planned. To investigate the impact of intra-fractional abdominal motions on delivered dose, anatomical deformations due to these three motion modes were extracted from dynamic MRI data using a previously developed hierarchical motion modeling methodology.Approach. Motion magnitudes were extracted from deformation fields between a reference state and all other motion states of the patient. Delivered dose estimates to various gastrointestinal organs (stomach, duodenum, small bowel and colon) were calculated on each motion state of the patient and accumulated to estimate the delivered dose to each organ for the entire treatment fraction.Main results. Across a sample of 10 patients, maximal motions of 33.6, 33.4, 47.6 and 49.2 mm were observed over 20 min for the stomach, duodenum, small bowel and colon respectively. Dose accumulation results showed that motions could lead to average increases of 2.0, 2.1, 1.1, 0.7 Gy to the maximum dose to 0.5cc (D0.5cc) and 3.0, 2.5, 1.3, 0.9 Gy to the maximum dose to 0.1cc (D0.1cc) for these organs at risk. From the 40 dose accumulations performed (10 for each organ at risk), 27 showed increases of modeled delivered dose compared to planned doses, 4 of which exceeded planned dose constraints.Significance. The use of intra-fraction motion measurements to accumulate delivered doses is feasible, and supports retrospective estimation of dose delivery to improve estimates of delivered doses, and further guide strategies for both plan adaptation as well as advances in intra-fraction motion management.

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update.

PURPOSE: This updated report on image guided radiation therapy (IGRT) is part of a series of consensus-based white papers previously published by the American Society for Radiation Oncology addressing patient safety. Since the first white papers were published, IGRT technology and procedures have progressed significantly such that these procedures are now more commonly used. The use of IGRT has now extended beyond high-precision treatments, such as stereotactic radiosurgery and stereotactic body radiation therapy, and into routine clinical practice for many treatment techniques and anatomic sites. Therefore, quality and patient safety considerations for these techniques remain an important area of focus. METHODS AND MATERIALS: The American Society for Radiation Oncology convened an interdisciplinary task force to assess the original IGRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology, and task force members indicated their level of agreement based on a 5-point Likert scale from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who selected "strongly agree" or "agree" indicated consensus. SUMMARY: This IGRT white paper builds on the previous version and uses other guidance documents to primarily focus on processes related to quality and safety. IGRT requires an interdisciplinary team-based approach, staffed by appropriately trained specialists, as well as significant personnel resources, specialized technology, and implementation time. A thorough feasibility analysis of resources is required to achieve the clinical and technical goals and should be discussed with all personnel before undertaking new imaging techniques. A comprehensive quality-assurance program must be developed, using established guidance, to ensure IGRT is performed in a safe and effective manner. As IGRT technologies continue to improve or emerge, existing practice guidelines should be reviewed or updated regularly according to the latest American Association of Physicists in Medicine Task Group reports or guidelines. Patient safety in the application of IGRT is everyone's responsibility, and professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working together to ensure the highest levels of safety.

Real-time prediction of stomach motions based upon gastric contraction and breathing models.

Objective.Precision radiation therapy requires managing motions of organs at risk that occur during treatment. While methods have been developed for real-time respiratory motion tracking, non-breathing intra-fractional variations (including gastric contractile motion) have seen little attention to date. The purpose of this study is to develop a cyclic gastric contractile motion prediction model to support real-time management during radiotherapy.Approach. The observed short-term reproducibility of gastric contractile motion permitted development of a prediction model that (1) extracts gastric contraction motion phases from few minutes of golden angle stack of stars scanning (at patient positioning), (2) estimate gastric phase of real-time sampled data acquired during treatment delivery to these reconstructed phases and (3) predicting future gastric phase by linear extrapolation using estimation results from step 2 to account for processing and system latency times. Model was evaluated on three parameters including training time window for step 1, number of spokes for real-time sampling data in step 2 and future prediction time. Mainresults. The model was tested on a population of 20 min data samples from 25 scans from 15 patients. The mean prediction error with 10 spokes and 2 min training was 0.3 ± 0.1 mm (0.1-0.7 mm) with 5.1 s future time, slowly rising to 0.6 ± 0.2 mm (0.2-1.1 mm) for 6.8 s future time and then increasing rapidly for longer forward predictions, for an average 3.6 ± 0.5 mm (2.8-4.7 mm) HD95 of gastric motion. Results showed that reducing of train time window (5-2 min) does not influence the prediction performance, while using 5 spokes increased prediction errors.Significance. The proposed gastric motion prediction model has sufficiently accurate prediction performance to allow for sub-millimeter accuracy while allowing sufficient time for data processing and machine interaction and shows the potential for clinical implementation to support stomach motion tracking during radiotherapy.

Lutetium-177 Prostate-Specific Membrane Antigen Therapy: A Practical Review.

Prostate-specific membrane antigen is a transmembrane protein found predominately on prostate epithelium and is expressed at high levels in prostate cancer. In this review, we discuss the background, clinical data, patient selection, side effects, and necessary resources to deliver lutetium-177 prostate-specific membrane antigen in the research setting, or as standard of care if approved by the United States Food and Drug Administration. Targeted radionuclide therapeutics require understanding of fundamental principles of radiobiology and physics, and radiation oncologists and medical physicists are well-suited to play an integral role in their delivery and treatment response monitoring as key components of a multidisciplinary care team.

Lutetium-177 DOTATATE: A Practical Review.

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that originate in endocrine tissues throughout the body. Though most are indolent, clinical outcomes vary greatly based on histologic differentiation and grade. Peptide receptor radionuclide therapy has emerged as a promising treatment for patients with locally advanced and/or metastatic disease refractory to standard of care treatment. The phase III NETTER-1 trial found that [177Lu] Lu-DOTA-[Tyr3]-octreotate improved disease-free survival versus octreotide alone for somatostatin receptor-positive gastroenteropancreatic NETs and had a favorable toxicity profile, leading to Food and Drug Administration approval. [177Lu] Lu-DOTA-[Tyr3]-octreotate is an important new treatment that expands the role of radiation in the treatment of NETs. Several important trials are ongoing to better elucidate the role of this treatment.

Rigid and Deformable Image Registration for Radiation Therapy: A Self-Study Evaluation Guide for NRG Oncology Clinical Trial Participation.

PURPOSE: The registration of multiple imaging studies to radiation therapy computed tomography simulation, including magnetic resonance imaging, positron emission tomography-computed tomography, etc. is a widely used strategy in radiation oncology treatment planning, and these registrations have valuable roles in image guidance, dose composition/accumulation, and treatment delivery adaptation. The NRG Oncology Medical Physics subcommittee formed a working group to investigate feasible workflows for a self-study credentialing process of image registration commissioning. METHODS AND MATERIALS: The American Association of Physicists in Medicine (AAPM) Task Group 132 (TG132) report on the use of image registration and fusion algorithms in radiation therapy provides basic guidelines for quality assurance and quality control of the image registration algorithms and the overall clinical process. The report recommends a series of tests and the corresponding metrics that should be evaluated and reported during commissioning and routine quality assurance, as well as a set of recommendations for vendors. The NRG Oncology medical physics subcommittee working group found incompatibility of some digital phantoms with commercial systems. Thus, there is still a need to provide further recommendations in terms of compatible digital phantoms, clinical feasible workflow, and achievable thresholds, especially for future clinical trials involving deformable image registration algorithms. Nine institutions participated and evaluated 4 commonly used commercial imaging registration software and various versions in the field of radiation oncology. RESULTS AND CONCLUSIONS: The NRG Oncology Working Group on image registration commissioning herein provides recommendations on the use of digital phantom/data sets and analytical software access for institutions and clinics to perform their own self-study evaluation of commercial imaging systems that might be employed for coregistration in radiation therapy treatment planning and image guidance procedures. Evaluation metrics and their corresponding values were given as guidelines to establish practical tolerances. Vendor compliance for image registration commissioning was evaluated, and recommendations were given for future development.

Modeling intra-fractional abdominal configuration changes using breathing motion-corrected radial MRI.

Abdominal organ motions introduce geometric uncertainties to gastrointestinal radiotherapy. This study investigated slow drifting motion induced by changes of internal anatomic organ arrangements using a 3D radial MRI sequence with a scan length of 20 min. Breathing motion and cyclic GI motion were first removed through multi-temporal resolution image reconstruction. Slow drifting motion analysis was performed using an image time series consisting of 72 image volumes with a temporal sampling rate of 17 s. B-spline deformable registration was performed to align image volumes of the time series to a reference volume. The resulting deformation fields were used for motion velocity evaluation and patient-specific motion model construction through principal component analysis (PCA). Geometric uncertainties introduced by slow drifting motion were assessed by Hausdorff distances between unions of organs at risk (OARs) at different motion states and reference OAR contours as well as probabilistic distributions of OARs predicted using the PCA model. Thirteen examinations from 11 patients were included in this study. The averaged motion velocities ranged from 0.8 to 1.9 mm min-1, 0.7 to 1.6 mm min-1, 0.6 to 2.0 mm min-1and 0.7 to 1.4 mm min-1for the small bowel, colon, duodenum and stomach respectively; the averaged Hausdorff distances were 5.6 mm, 5.3 mm, 5.1 mm and 4.6 mm. On average, a margin larger than 4.5 mm was needed to cover a space with OAR occupancy probability higher than 55%. Temporal variations of geometric uncertainties were evaluated by comparing across four 5 min sub-scans extracted from the full scan. Standard deviations of Hausdorff distances across sub-scans were less than 1 mm for most examinations, indicating stability of relative margin estimates from separate time windows. These results suggested slow drifting motion of GI organs is significant and geometric uncertainties introduced by such motion should be accounted for during radiotherapy planning and delivery.

A hierarchical model of abdominal configuration changes extracted from golden angle radial magnetic resonance imaging.

Abdominal organs are subject to a variety of physiological forces that superimpose their effects to influence local motion and configuration. These forces not only include breathing, but can also arise from cyclic antral contractions and a range of slow configuration changes. To elucidate each individual motion pattern as well as their combined effects, a hierarchical motion model was built for characterization of these 3 motion modes (characterized as deformation maps between states) using golden angle radial MR signals. Breathing motions are characterized first. Antral contraction states are then reconstructed after breathing motion-induced deformation are corrected; slow configuration change states are further extracted from breathing motion-corrected image reconstructions. The hierarchical model is established based on these multimodal states, which can be either individually shown or combined to demonstrate any arbitrary composited motion patterns. The model was evaluated using 20 MR scans acquired from 9 subjects. Poor reproducibility of breathing motions both within as well as between scan sessions was observed, with an average intra-subject difference of 1.6 cycles min-1 for average breathing frequencies of 12.0 cycles min-1. Antral contraction frequency distributions were more stable than breathing, but also presented poor reproducibility between scans with an average difference of 0.3 cycles min-1 for average frequencies of 3.2 cycles min-1. The magnitudes of motions beyond breathing were found to be significant, with 14.4 and 33.8 mm maximal motions measured from antral contraction and slow configuration changes, respectively. Hierarchical motion models have potential in multiple applications in radiotherapy, including improving the accuracy of dose delivery estimation, providing guidance for margin creation, and supporting advanced decisions and strategies for immobilization, treatment monitoring and gating.

The Fusion of Incident Learning and Failure Mode and Effects Analysis for Data-Driven Patient Safety Improvements.

PURPOSE: Incident learning is a critical part of the quality improvement process for all radiation therapy clinics. Failure mode and effects analysis has also been adopted as a hazard analysis method within the field of radiation oncology based on the recommendations of American Association of Physicists in Medicine Task Group 100. In this work, we demonstrate a fusion of these techniques that is efficient and transferrable to all types of clinics and that allows data-driven targeting of the highest risk error types. METHODS AND MATERIALS: Four clinical physicists recorded safety events detected during physics treatment plan quality assurance over a 27-month period. Events were sorted into the broad categories of either a documentation or plan construction error. Events were further stratified into subcategories until sufficiently discriminated against for analysis. Event risks were quantified using reduced-resolution TG-100 severity scores combined with observed occurrence rates. The highest risk categories were examined for intervention strategies. RESULTS: A total of 871 events were identified over the study period. Of these, 652 (74.9%) were classified as low severity, 178 (20.4%) as medium severity, and 41 (4.7%) as high severity. Four of the top 5 ranked categories could be targeted by a preplanning chart rounds. Several of the categories could be targeted by additional automation in the planning and QA processes. CONCLUSIONS: The retrospective classification and risk analysis of safety events allows clinics to design targeted workflow and quality assurance changes aimed at reducing the occurrence of high-risk events. The method presented here leverages incident learning efforts that many clinics are already performing, allows the severity of events to be efficiently assigned, and generates actionable results without requiring a complete failure mode and effects analysis.

Single-Institution Phase 1/2 Prospective Clinical Trial of Single-Fraction, High-Gradient Adjuvant Partial-Breast Irradiation for Hormone Sensitive Stage 0-I Breast Cancer.

PURPOSE: We sought to evaluate the feasibility and tolerability of a novel accelerated partial breast irradiation regimen delivered in a single fraction postoperatively. METHODS AND MATERIALS: We enrolled 50 patients with low-risk, hormone-sensitive breast cancer from 2015 to 2018 on a prospective phase 1/2 trial to receive single-fraction, high-gradient partial-breast irradiation (SFHGPBI) 2 to 8 weeks after lumpectomy for node-negative, invasive, or in situ breast cancer. The high gradient was achieved by prescribing 20 Gy to the surgical bed and 5 Gy to the breast tissue within 1 cm of the surgical bed simultaneously in 1 fraction using external beam. RESULTS: The median age was 65 (range, 52-84). Ten patients (20%) had small-volume ductal carcinoma in situ while the remainder had stage I disease. At a median follow-up of 25 months, we evaluated toxicity, patient- and physician-reported cosmesis, patient-reported quality of life (QOL), and initial tumor control. There was no Common Terminology Criteria for Adverse Events v4.0 grade 3+ toxicity. Only 34% of patients experienced grade 1 erythema. Good-to-excellent pretreatment cosmesis was present in 100% and 98% per physicians and patients, respectively, and did not change post-SFHGPBI. Quantitative cosmesis by percentage of breast retraction assessment significantly improved over time during the post-SFHGPBI period per mixed repeated measures modeling (P = .0026). QOL per European Organization for Research and Treatment of Cancer QOL Questionnaires C30 and BR-23 did not decline other than temporarily in the systemic therapy effects and hair loss domains, both of which returned to pretreatment values. There was 1 noninvasive in-breast recurrence in a separate untreated quadrant 18 months post-SFHGPBI and 1 isolated axillary recurrence 30 months post-SFHGPBI, both salvaged successfully. There were no distant recurrences or cancer-related deaths observed. CONCLUSIONS: Accelerated partial-breast irradiation delivered in a single fraction postoperatively using external beam techniques is a novel, feasible, well-tolerated regimen. SFHGPBI does not adversely affect cosmesis or QOL as reported by both physicians and patients. Initial tumor control rates are excellent, with longer follow-up required to confirm efficacy.

The Special Medical Physics Consult Process for Reirradiation Patients.

PURPOSE: To present a systematic approach to the reirradiation special medical physics consult (ReRT-SMPC) process. MATERIALS AND METHODS: An in-house reirradiation committee of physicians and physicists was formed to develop a streamlined and well-documented approach to ReRT-SMPCs. Dosimetric goals and considerations for tissue repair were generated by the committee with input from the literature, clinical trial guidelines, and physician experience. Procedural workflow was also defined. RESULTS: The total number of ReRT-SMPCs performed in our department in 2018 was 401, corresponding to 369 unique patients and 16% of the total number of patients receiving external beam radiation in our department that year. This constituted a large increase over the 183 ReRT-SMPCs performed in 2017. We have found that a standardized ReRT-SMPC workflow helps to safeguard patients, documents the clinical decision-making process for medical and legal purposes, and facilitates the peer-review process. The data being collected from each consult along with toxicity and outcomes data can be used to help inform future re-treatment guidelines. CONCLUSIONS: As the number of patients returning for additional courses of radiation continues to increase, a uniform method for the ReRT-SMPC workflow and analysis is a powerful tool for ensuring patient safety, understanding and predicting treatment toxicity, and refining reirradiation dosimetric limits.

Functional Adaptation in Radiation Therapy.

The promise of adaptive therapy to improve outcomes in radiation oncology has been an area of interest and research in the community for many years. One of the sources of data that can be used to drive adaptive therapy is functional information about the tumor or normal tissues. This avenue of adaptation includes many potential sources of data including global markers and functional imaging. Global markers can be assessments derived from blood measurements, patient functional testing, and circulating tumor material and functional imaging data comprises spatial physiological information from various imaging studies such as positron emission tomography, magnetic resonance imaging, and single photon emission computed tomography. The goal of functional adaptation is to use these functional data to adapt radiation therapy to improve patient outcomes. While functional adaptation holds a lot of promise, there are challenges such as quantifying and minimizing uncertainties, streamlining clinical implementation, determining the ideal way to incorporate information within treatment plan optimization, and proving the clinical benefit through trials. This paper will discuss the types of functional information currently being used for adaptation, highlight several areas where functional adaptation has been studied, and introduce some of the barriers to more widespread clinical implementation.

A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy.

PURPOSE: Daily magnetic resonance (MR)-guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment. METHODS AND MATERIALS: Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test. RESULTS: The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively. CONCLUSIONS: This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for Ultracentral Thorax Malignancies: Results of a Phase 1 Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial. METHODS AND MATERIALS: Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded. RESULTS: All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified. CONCLUSIONS: SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.

Stereotactic Body Radiation Therapy for Central Early-Stage NSCLC: Results of a Prospective Phase I/II Trial.

INTRODUCTION: We report results from a prospective phase I/II trial for patients with centrally located, early-stage NSCLC receiving stereotactic body radiation therapy. METHODS: Eligible patients were medically inoperable with biopsy-proven NSCLC within 2 cm of the proximal bronchial tree or 5 mm of the mediastinal pleura or parietal pericardium. Phase I had four dose levels using 5 fractions: 9, 10, 11, and 12 Gy per fraction. The primary phase II objective was to determine if the maximum tolerated dose in phase I achieved local control greater than 80% at 2 years. RESULTS: Seventy-four patients were enrolled; 23 to phase I and 51 to phase II. Two phase I patients treated with 10 Gy × 5 fractions developed unrelated acute grade 3 lung toxicities which resolved. The phase II dose level selected was 11 Gy × 5 fractions. The median follow-up for living phase II patients was 27 months (range, 9 to 58 months). Two-year local control using 11 Gy × 5 fractions was 85% (95% confidence interval [CI]: 62%-95%). Two-year overall survival was 43% (95% CI: 28%-57%). Three patients (6%, 95% CI: 1%-17%) experienced acute grade 3 and 4 cardiac or pulmonary toxicities. Of the 41 patients evaluable for late cardiac and pulmonary toxicity, 11 (27%, 95% CI: 14%-43%) developed grade 3, 5 (12%, 95% CI: 4%-26%) developed grade 4, and 1 (4%, 95% CI: 0%-13%) died of grade 5 toxicity. CONCLUSION: Stereotactic body radiation therapy for central NSCLC using 11 Gy × 5 fractions is tolerable and has excellent local control, but is associated severe late toxicity in some patients.

In Silico Trial of MR-Guided Midtreatment Adaptive Planning for Hypofractionated Stereotactic Radiation Therapy in Centrally Located Thoracic Tumors.

PURPOSE: Hypofractionated (>5 fraction) stereotactic radiation therapy (HSRT) may allow for ablative biologically equivalent dose to tumors with a lower risk of organ-at-risk (OAR) toxicity in central thoracic tumors. Adaptive planning may further improve OAR sparing while maintaining planning target volume (PTV) coverage. We hypothesized that midtreatment adaptive replanning would offer dosimetric advantages during HSRT for central thorax malignancies using magnetic resonance imaging (MRI)-guided radiation therapy. METHODS AND MATERIALS: Twelve patients with central thorax tumors received HSRT using MRI-guided radiation therapy. Clinically delivered regimens were 60 Gy in 12 fractions or 62.5 Gy in 10 fractions, with low-field magnetic resonance (0.35 T) volumetric setup imaging acquired at each fraction. Daily gross tumor volume (GTV) and OARs were retrospectively redefined on fraction 1, 6, and 10 MRIs, and GTV response was recorded. Simulated initial plans prescribed a dose of 60 Gy in 12 fractions based on fraction 1 MRI. Midtreatment adaptive plans were created based on fraction 6 anatomy-of-the-day. All plans were created using an isotoxicity approach with a goal of 95% PTV coverage, subject to hard OAR constraints, to represent clinically ideal OAR sparing. Plans were then compared for projected OAR sparing and PTV coverage. RESULTS: Patients demonstrated significant on-treatment MRI-defined GTV reduction (median 41.8%; range 16.7%-65.7%). At fraction 6, median reduction was 26.7%. All initial plans met OAR constraints. Initial plan application to fraction 6 and fraction 10 anatomy resulted in 8 OAR violations (5 of 13 patients) and 10 OAR violations (6 of 13 patients). All fraction 6 violations persisted at fraction 10. Midpoint adaptive planning reversed 100% of midpoint OAR violations and tended to reduce the magnitude of OAR violations incurred at fraction 10. In 40% of fractions (2 of 5) in which OAR violation resulted from initial plan application to fraction 6 anatomy, PTV coverage was increased concomitant with violation reversal. CONCLUSIONS: Midtreatment adaptive planning based on tumor response may be dosimetrically advantageous for sparing of surrounding critical structures in HSRT for central thorax malignancies and could be applied using either an online or offline paradigm.