Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT. METHODS: Three hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator's discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used. DISCUSSION: The MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020. https://clinicaltrials.gov/ct2/show/NCT04384770 PROTOCOL VERSION: Version 2.1, Aug 28, 2020.

Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film.

PURPOSE: Magnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV. METHODS: The motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique. RESULTS: Without gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm. CONCLUSIONS: Our results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study.

Credentialing of stereotactic radiosurgery and stereotactic body radiation therapy programs for quality and safety: The Novalis Certified Program.

The expectation of quality and safety is a fundamental tenet in all areas of healthcare, and a cornerstone of best practice is a process of continuous learning and continuous improvement. Independent audits and peer review of radiotherapy programs are an important mechanism for identifying process or technology gaps, for highlighting areas for improvement, and for incorporating within continuous improvement processes. In the field of radiotherapy, independent certification programs exist within various national and/or professional spheres, yet few focus specifically on specialty procedures such as radiosurgery or brachytherapy, despite several recommendations for such programs. In this manuscript we describe a specialized SRS/SBRT credentialing program founded on national/international standards and guidelines. We also present the results of an anonymous survey from institutions who have completed the program.

Results of an Artificial Intelligence-Based Image Review System to Detect Patient Misalignment Errors in a Multi-institutional Database of Cone Beam Computed Tomography-Guided Radiation Therapy.

PURPOSE: Present knowledge of patient setup and alignment errors in image guided radiation therapy (IGRT) relies on voluntary reporting, which is thought to underestimate error frequencies. A manual retrospective patient-setup misalignment error search is infeasible owing to the bulk of cases to be reviewed. We applied a deep learning-based misalignment error detection algorithm (EDA) to perform a fully automated retrospective error search of clinical IGRT databases and determine an absolute gross patient misalignment error rate. METHODS AND MATERIALS: The EDA was developed to analyze the registration between planning scans and pretreatment cone beam computed tomography scans, outputting a misalignment score ranging from 0 (most unlikely) to 1 (most likely). The algorithm was trained using simulated translational errors on a data set obtained from 680 patients treated at 2 radiation therapy clinics between 2017 and 2022. A receiver operating characteristic analysis was performed to obtain target thresholds. DICOM Query and Retrieval software was integrated with the EDA to interact with the clinical database and fully automate data retrieval and analysis during a retrospective error search from 2016 to 2017 and from 2021 to 2022 for the 2 institutions, respectively. Registrations were flagged for human review using both a hard-thresholding method and a prediction trending analysis over each individual patient's treatment course. Flagged registrations were manually reviewed and categorized as errors (>1 cm misalignment at the target) or nonerrors. RESULTS: A total of 17,612 registrations were analyzed by the EDA, resulting in 7.7% flagged events. Three previously reported errors were successfully flagged by the EDA, and 4 previously unreported vertebral body misalignment errors were discovered during case reviews. False positive cases often displayed substantial image artifacts, patient rotation, and soft tissue anatomy changes. CONCLUSIONS: Our results validated the clinical utility of the EDA for bulk image reviews and highlighted the reliability and safety of IGRT, with an absolute gross patient misalignment error rate of 0.04% ± 0.02% per delivered fraction.

Intraoperative ultrasonography-guided positioning of iodine 125 plaque brachytherapy in the treatment of choroidal melanoma.

PURPOSE: To report intraoperative ultrasonography-guided positioning of iodine 125 (I(125)) plaques for brachytherapy of choroidal melanoma as a quality improvement measure. DESIGN: Retrospective, single-center, consecutive case-cohort study. PARTICIPANTS: One hundred fifty consecutive patients with choroidal melanoma. METHODS: Patients with choroidal melanoma who were treated with I(125) plaque brachytherapy from January 2007 through January 2011 with at least 6 months of clinical follow-up were included. MAIN OUTCOME MEASURES: Patient and tumor characteristics at diagnosis were tabulated. The need for plaque repositioning if intraoperative ultrasonography showed the plaque to be either not centered on the tumor or if there was less than 1.0 mm of plaque margin beyond the tumor border was recorded. The rate of local treatment failure and occurrence of distant metastasis were determined. RESULTS: The average interval from surgery to last follow-up was 21.5 months. Fifty-four (36%) of 150 patients required plaque repositioning. Of tumors located in the macula, equator, and periphery, 15 (36.6%), 26 (36.6%), and 13 (34.2%) required repositioning. There was no case of local treatment failure during a mean follow-up of 21.5 months (range, 6-48 months). Clinical evidence of choroidal melanoma metastasis developed in 9 patients. The cumulative 2-year Kaplan-Meier rate of local treatment failure in the cohort was statistically lower compared with the Collaborative Ocular Melanoma Study, which did not require ultrasonography-guided plaque positioning. CONCLUSIONS: Intraoperative ultrasonography identified the need to reposition I(125) plaques to achieve centration and plaque margin (>1.0 mm) beyond the tumor border in 36% of eyes. Neither tumor size nor tumor location correlated with the need to reposition the plaque. There was no case of local treatment failure during follow-up in this series. Correct plaque position is an essential component of quality outcomes in brachytherapy. Intraoperative ultrasonography reduces geographic errors in placement in eye plaque therapy and may help to reduce local treatment failure in choroidal melanoma.

Prostate-Centric Versus Bony-Centric Registration in the Definitive Treatment of Node-Positive Prostate Cancer with Simultaneous Integrated Boost: A Dosimetric Comparison.

Purpose: To determine the effect of daily shifts based on rigid registration to intraprostatic markers on coverage of boost doses delivered to gross nodal disease for prostate cancer. Methods and Materials: Seventy-five cone beam computed tomographies (CBCTs) from 15 patients treated with definitive radiation for clinically node-positive prostate cancer underwent fiducial-based and pelvic bony-based registration to the initial planning scans. Gross tumor volumes of nodal boost targets were contoured directly on each CBCT registration. The nodal displacement (3-dimensional translation from the node centroid on planning CT to node centroid on registered CBCT) and dose coverage (minimum dose [Dmin], mean dose [Dmean], dose delivered to 95% of the gross tumor volumes [D95]) were calculated for each registration on all nodal targets. All doses for each node were normalized to its intended prescription dose (dose covering 95% of a 3 mm planning target volume [PTV] expansion). Results: Forty-one gross nodal targets were analyzed. Most boosted nodes (80.5%, 33/41) were treated with conventional fractionation using volumetric-arc radiation therapy, and 19.5% (8/41) underwent stereotactic body radiation therapy (SBRT). Dmin, Dmean, and D95 were all significantly lower with fiducial-based registration compared with bony-based registration (P < .0001). Nodal displacement was significantly higher for fiducial-based registrations (P < .0001). The 3-dimensional translation between the fiducial-based and bony-based registrations (bony-to-fiducial vector) was the most significant predictor of nodal displacement (P < .0001). On fiducial-based registrations, a 3 to 5 mm gross nodal PTV margin is sufficient in most directions; however, superior and posterior margins of 8 to 9 mm are required as a result of asymmetrical prostatic motion. Conclusions: Large and anisotropic PTV margins are likely needed to adequately dose gross nodal targets when patient setup is based on rigid registration to intraprostatic markers. Alternative approaches such as adaptive replanning may be required to overcome these limitations.

Practical Considerations for Single Isocenter LINAC Radiosurgery of Multiple Brain Metastases.

The purpose of this paper is to summarize treatment guidelines for the performance of single isocenter LINAC radiosurgery of multiple brain metastases developed and used by 3 experienced centers. This article is not meant to provide consensus guidelines. Rather, this is a practical, "how we do it" reference without substantial discussion. To serve as a treatment reference, the great majority of the information is presented in topic-specific tables.

Intra-Fraction Motion Management for Radiosurgical Treatments of Trigeminal Neuralgia: Clinical Experience, Imaging Frequency, and Motion Analysis.

Purpose The aim of this study is to evaluate the patient positioning and intra-fraction motion management performance of an image-guidance protocol established for radiosurgical treatments of trigeminal neuralgia patients. Specifically, it also aims to analyze patient motion data for the evaluation of current motion tolerance levels and imaging frequency utilized for repositioning patients. Methods A linear accelerator equipped with ExacTrac is used for patient positioning with stereoscopic imaging and treatments. Treatments are delivered with 4-mm conical collimators using seven equally spaced arcs. Arcs are 20 degrees apart and span 100 arc degrees each. Following initial ExacTrac positioning, cone beam computed tomography (CBCT) is obtained for independent confirmation of patient position. Patients are then stereoscopically imaged prior to the delivery of each arc and repositioned when 0.5-mm translational tolerance in any direction is exceeded. After the patient has been repositioned, verification stereoscopic images are obtained. Data from 48 patients with 607 image pairs were analyzed for this study. Results Over the course of 48 patient treatments, the mean magnitude of mean 3D deviations was 0.64 mm ± 0.12 mm (range: 0.07-2.74 mm). With the current 0.50-mm tolerance level for repositioning, patients exceeded the tolerance 51.4% of the time considering only images following an arc segment. For those instances, patients were repositioned with a mean magnitude of 0.85 mm ± 0.15 mm (1 SD). For a 0.25-mm tolerance level, 86.1% of arc segments would have required repositioning following the delivery of an arc segment, with a mean magnitude of 0.68 mm ± 0.12 mm. Conversely, for 0.75-mm and 1.00-mm tolerance levels, the tolerance would have been exceeded only 21.5% and 6.6% of instances following the delivery of an arc segment, with a mean magnitude of 1.08 mm ± 0.21 mm and 1.34 mm ± 0.24 mm, respectively. Each repositioning adds approximately 2 minutes to treatment time, which accounts for parts of the variability in patient treatment times. Following the initial ExacTrac and CBCT, the mean treatment time from first arc to treatment end was 57 minutes (range: 33-63 minutes). Discussions The current 0.50-mm tolerance level results in a clinically manageable but significant number of patient repositions during trigeminal neuralgia treatments. Frequent patient repositioning can result from actual patient motion convolved with the accuracy and precision limitations of the image analysis. Increasing the repositioning tolerance could more selectively correct for actual patient motion and shorten the treatment time at the expense of more variations in patient position. A more lenient tolerance level of 0.75 mm would decrease the repositioning rate by approximately a factor of 2; however, the permissible magnitude of motion will increase, leading to possible dosimetric consequences. Once treatment begins, there was no trend as to when patients exceeded the tolerance. Conclusions Current imaging protocol for patient positioning and intra-fraction motion management fits the clinical workflow with clinically acceptable residual patient motion. The next important step would be to assess how the number of repositions and magnitude of residual movements affect treatment outcomes.

A Framework for Sharing Radiation Dose Distribution Maps in the Electronic Medical Record for Improving Multidisciplinary Patient Management.

Radiation oncology practices use a suite of dedicated software and hardware that are not common to other medical subspecialties, making radiation treatment history inaccessible to colleagues. A radiation dose distribution map is generated for each patient internally that allows for visualization of the dose given to each anatomic structure volumetrically; however, this crucial information is not shared systematically to multidisciplinary medical, surgery, and radiology colleagues. A framework was developed in which dose distribution volumes are uploaded onto the medical center's picture archiving and communication system (PACS) to rapidly retrieve and review exactly where, when, and to what dose a lesion or structure was treated. The ability to easily visualize radiation therapy information allows radiology clinics to incorporate radiation dose into image interpretation without direct access to radiation oncology planning software and data. Tumor board discussions are simplified by incorporating radiation therapy information collectively in real time, and daily onboard imaging can also be uploaded while a patient is still undergoing radiation therapy. Placing dose distribution information into PACS facilitates central access into the electronic medical record and provides a succinct visual summary of a patient's radiation history for all medical providers. More broadly, the radiation dose map provides greater visibility and facilitates incorporation of a patient's radiation history to improve oncologic decision making and patient outcomes. Keywords: Brain/Brain Stem, CNS, MRI, Neuro-Oncology, Radiation Effects, Radiation Therapy, Radiation Therapy/Oncology, Radiosurgery, Skull Base, Spine, Technology Assessment Supplemental material is available for this article. © RSNA, 2021 See also commentary by Khandelwal and Scarboro in this issue.

Simultaneous radiosurgery for multiple brain metastases: technical overview of the UCLA experience.

PURPOSE/OBJECTIVE(S): To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins. MATERIALS/METHODS: Eight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0 mm, 1 mm and 2 mm margins were created, including plans with variable margins, where targets more than 6 cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements. RESULTS: The V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from 0 to 1 mm and tripled when change from 0 to 2 mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6 cm away from the isocenter. With 0.5 mm re-positioning threshold, 57.4% of the time the patients are repositioned. Reducing the threshold to 0.25 mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. The 90th percentile of translational movements in all directions is 0.7 mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2 mm and 0.2 degrees, respectively. CONCLUSIONS: Based on the data presented, we have switched our modus operandi from 2 to 1 mm PTV margins, with an eventual goal of using 0.5 and 1.0 mm variable margins when an automated margin assignment method becomes available. The 0.5 mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements.

Missing the Near Miss: Recognizing Valuable Learning Opportunities in Radiation Oncology.

PURPOSE: "Near miss" events are valuable low-cost learning opportunities in radiation oncology as they do not result in patient harm and are more pervasive than adverse events that do. Near misses vary depending on the presence of a latent error of behavior or process, and the presence of an enabling condition predisposing the patient to harm. These nuanced distinctions across near miss types can elicit different cognitive biases affecting the recognition of near misses as learning opportunities. We define near miss types in radiation oncology and explore the differential perceptions among radiation oncology staff. METHODS AND MATERIALS: Six event types were defined based on attributes of latent error and enabling conditions: "hit," "potential hit," "almost happened," "fortuitous catch," "could have happened," and "process-based catch." These events were illustrated with an example of a patient receiving pacemaker cardiac clearance before radiation treatment. A survey assessing (1) success versus failure of an event and (2) willingness to report the event was administered to a radiation oncology department using the pacemaker example. Mean scores for each near miss type were compared. RESULTS: Ninety-five staff members (74%) completed the survey. Perceived success scores and willing-to-report scores significantly differed by near miss type (P = .042 for success ratings; P < .0001 for willingness to report). "Could have happened" events were viewed as less successful and were more likely to be reported than "almost happened" events (P < .0001). CONCLUSIONS: Cognitive biases appear to influence whether and how near miss types are recognized as report-worthy. Education of near miss types and engaging staff for quality improvement may improve recognition.

Clinical outcomes of stereotactic magnetic resonance image-guided adaptive radiotherapy for primary and metastatic tumors in the abdomen and pelvis.

PURPOSE: Stereotactic body radiotherapy (SBRT) delivers ablative doses with excellent local control. However, implementing SBRT for abdominal and pelvic tumors has been limited by the risk for treatment-related gastrointestinal toxicity. MRI-guided radiotherapy may ameliorate these risks and increase the therapeutic ratio. We report the clinical outcomes of stereotactic MRI-guided adaptive radiotherapy (SMART) for primary and metastatic tumors in the abdomen and pelvis. METHODS: From November 2014 to August 2017, the first 106 consecutive patients with 121 tumors in the abdomen and pelvis were treated with SMART at a single institution. Of the cohort, 41.5%, 15.1%, and 43.4% had primary, locally recurrent, and oligometastatic tumors, respectively. SMART was delivered using a tri-cobalt-60 gantry with on-board 0.35 Tesla MRI with respiratory breath-hold and daily adaptive re-planning when anatomically necessary. A median of 40Gy in five fractions was prescribed. The Common Terminology Criteria for Adverse Events v.4.03 was used to score treatment-related toxicities. Local control (LC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method. RESULTS: Of the 510 treatments, seventy-one (13.9%) were adapted. Fatigue, nausea, and pain were the most common acute toxicities. 0.9 and 0% of patients experienced acute grade three and four toxicities, respectively. 5.2 and 2.1% of patients experienced late grade three and four toxicities, respectively. After a median follow-up of 20.4 months, the 2-year LC rate was 74% on a per-lesion basis. Two-year LC was 96% for lesions that were treated with BED10 ≥100 versus 69% for BED10 <100 (p = 0.02). PFS was significantly different between patients with and without locally controlled tumors (2-year PFS 21 vs. 8%, p = 0.03). Two-year OS was 57% for the entire cohort. CONCLUSIONS: Favorable LC and PFS outcomes were observed with minimal morbidity for tumors in the abdomen and pelvis treated with SMART. Future prospective clinical trials to validate these findings are warranted.

Dosimetric Quality of Online Adapted Pancreatic Cancer Treatment Plans on an MRI-Guided Radiation Therapy System.

PURPOSE: Stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) is an emerging technique that shows promise in the treatment of pancreatic cancer and other abdominopelvic malignancies. However, it is unknown whether the time-limited nature of on-table adaptive planning may result in dosimetrically suboptimal plans. The purpose of this study was to quantitatively address that question through systemic retrospective replanning of treated on-table adaptive pancreatic cancer cases. METHODS AND MATERIALS: Of 74 consecutive adapted fractions, 30 were retrospectively replanned based on deficiencies in planning target volume (PTV) and gross tumor volume (GTV) coverage or doses to organs-at-risk (OARs) that exceeded ideal constraints. Retrospective plans were created by adjusting dose-volume objectives in an iterative fashion until deemed optimized. The goal of replanning was to improve PTV/GTV coverage while keeping the dose to gastrointestinal OARs the same or lower or to reduce OAR doses while keeping PTV coverage the same or higher. The global maximum dose was required to be maintained within 2% of that of the treated adaptive plan to eliminate it as a confounding factor. A threshold of 5% improvement in PTV coverage or 5% decrease in OAR dose was used to define a clinically significant improvement. RESULTS: Of the 30 replans, 7 obtained at least 5% PTV coverage improvement. The average increase in PTV coverage for these plans was 11%. No plans were clinically significantly improved in terms of OAR sparing. Changes in beam-on time did not show any correlation. Statistical analysis via a linear mixed-effects model with a nested random effect suggested that both GTV and PTV coverage were improved over SMART process plans by 0.91 cc (P = .02) and 2.03 cc (P < .001), respectively. CONCLUSIONS: Dosimetric plan quality of at least 10% of SMART fractions may be improved through more extensive replanning than is currently performed on-table. Further work is needed to develop an automated replanning workflow to streamline the in-depth replanning process to better fit into an on-table adaptive workflow.

Linear accelerator-based radiosurgery for trigeminal neuralgia: comparative outcomes of frame-based and mask-based techniques.

OBJECTIVE: Precise and accurate targeting is critical to optimize outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). The aim of this study was to compare the outcomes after SRS for TN in which two different techniques were used: mask-based 4-mm cone versus frame-based 5-mm cone. METHODS: The authors performed a retrospective review of patients who underwent SRS for TN at their institution between 1996 and 2019. The Barrow Neurological Institute (BNI) pain score and facial hypesthesia scale were used to evaluate pain relief and facial numbness. RESULTS: A total of 234 patients were included in this study; the mean age was 67 years. In 97 patients (41.5%) radiation was collimated by a mask-based 4-mm cone, whereas a frame-based 5-mm cone was used in the remaining 137 patients (58.5%). The initial adequate pain control rate (BNI I-III) was 93.4% in the frame-based 5-mm group, compared to 87.6% in the mask-based 4-mm group. This difference between groups lasted, with an adequate pain control rate at ≥ 24 months of 89.9% and 77.8%, respectively. Pain relief was significantly different between groups from initial response until the last follow-up (≥ 24 months, p = 0.02). A new, permanent facial hypesthesia occurred in 30.3% of patients (33.6% in the frame-based 5-mm group vs 25.8% in the mask-based 4-mm group). However, no significant association between the BNI facial hypesthesia score and groups was found. Pain recurrence occurred earlier (median time to recurrence 12 months vs 29 months, p = 0.016) and more frequently (38.1% vs 20.4%, p = 0.003) in the mask-based 4-mm than in the frame-based 5-mm group. CONCLUSIONS: Frame-based 5-mm collimator SRS for TN resulted in a better long-term pain relief with similar toxicity profiles to that seen with mask-based 4-mm collimator SRS.

Dose-response with stereotactic body radiotherapy for prostate cancer: A multi-institutional analysis of prostate-specific antigen kinetics and biochemical control.

BACKGROUND AND PURPOSE: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens. MATERIALS AND METHODS: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS). RESULTS: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21). CONCLUSION: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma.

BACKGROUND: Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. METHODS: 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. RESULTS: Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. CONCLUSIONS: Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.

The Timeliness Initiative: Continuous Process Improvement for Prompt Initiation of Radiation Therapy Treatment.

PURPOSE: The ambulatory patient experience is heavily influenced by wait times for provider care. Delayed patient visit start times may negatively affect overall satisfaction, and increased wait times affect the perception of the information, instructions, and treatment given by health care providers. Improving institutional practices overall requires the determination of the essential quality metrics that will make such an achievement possible. A protracted time leading up to the initiation of radiation therapy may promote poor satisfaction and perceived quality of care for both patients and referring providers alike, which may then create a barrier to patients being treated with radiation therapy. This institution piloted and sucessfully completed a study into improving the timeliness of initiation of patient radiation therapy for our patients. METHODS AND MATERIALS: This work sought to identify inefficiencies in radiation therapy treatment planning to shorten the time each patient waited for treatment. We examined the time between simulation to the start of the first fraction of treatment. This period includes simulation, contouring, treatment planning, and quality assurance of the plan. RESULTS: Before the study, the planning process would typically take 2 weeks. Target and organs-at-risk contouring were found to be the main inefficiency delaying treatment start dates. This delineating process includes drawing contours on radiologic images, typically computed tomography and magnetic resonance imaging. We focused on the time needed for the contouring process to be completed and took steps to increase efficiency. The length of time from simulation to contour approval was decreased by more than 60%, a reduction from an average of more than 4 days to less than 1.5 days. Overall planning time dropped from 2 weeks to less than 5 days. CONCLUSIONS: Process improvements and implementation of task-specific tools improved the timeliness of patient treatments, reducing the overall planning time from simulation to treatments to less than 5 days. Continuous monitoring and modification of these processes revealed that the successes achieved toward better quality of care have been sustained.

Resilience vs. Vulnerability: Psychological Safety and Reporting of Near Misses with Varying Proximity to Harm in Radiation Oncology.

BACKGROUND: Psychological safety, a shared belief that interpersonal risk taking is safe, is an important determinant of incident reporting. However, how psychological safety affects near-miss reporting is unclear, as near misses contain contrasting cues that highlight both resilience ("we avoided failure") and vulnerability ("we nearly failed"). Near misses offer learning opportunities for addressing underlying causes of potential incidents, and it is crucial to understand what facilitates near-miss reporting. METHODS: A survey of radiation oncology department staff in an academic hospital assessed psychological safety and presented five scenarios with varying proximity to patient harm: "standard care" involving no harm, three near misses with varying proximity to harm ("could have happened," "fortuitous catch," "almost happened"), and one "hit" involving harm. Respondents evaluated each event as success or failure and reported willingness to report on a seven-point Likert scale. The analysis employed ordered logistic regression models. RESULTS: A total of 78 staff (61.4%) completed the survey. The odds of reporting "hit" (odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.19-3.23), "almost happened" (OR: 1.60, 95% CI: 1.07-2.37), and "fortuitous catch" (OR: 1.60, 95% CI: 1.10-2.33) improved with an increase in psychological safety. The relationship of psychological safety to reporting "standard care" and "could have happened" was not statistically significant. The odds of reporting were higher when a near miss was discerned as failure (vs. success). CONCLUSION: Near misses are not processed and reported equally. The effect of psychological safety on reporting near misses becomes stronger with their increasing proximity to a negative outcome. Educating health care workers to properly identify near misses and fostering psychological safety may increase near-miss reporting and improve patient safety.

Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) is an effective treatment of spinal metastases in the vertebral body. However, variation has existed between practitioners regarding the appropriate target delineation. As such, we compared the tumor control, rates of compression fractures, and pain control for patients who had undergone SBRT for spinal metastases to either the lesion only (LO) or the full vertebral body (FVB). METHODS: A total of 126 spinal metastases in 84 patients had received single-fraction SBRT from January 2009 to February 2015. Of the 126 lesions, 36 (29%) were in the FVB group and 90 were in the LO group. The SBRT plans were reviewed to determine the treatment volume. Odds ratios were used to compare the rates of compression fracture and local failure. Regression analysis was performed to identify the predictors of outcome. RESULTS: A total of 5 failures had occurred in the FVB group and 14 in the LO group; however, the difference was not statistically significant (P = 0.5). No difference was found in pain reduction between the 2 groups (P = 0.9). Seven post-treatment compression fractures occurred in the LO group and four in the FVB group; however, the difference was not statistically significant (P = 0.6). The minimum dose to the planning target volume, patient age, and planning target volume size were the only significant factors predicting for local failure, vertebral body fracture, and pain control, respectively. CONCLUSIONS: Given that we found no difference in tumor control, pain reduction, or fracture rate between patients treated to the FVB versus the. LO, it might be reasonable to consider SBRT to the LO for select patients.

Time-Driven Activity-Based Costing Comparison of CT-Guided Versus MR-Guided SBRT.

PURPOSE: Magnetic resonance-guided radiation therapy (MRgRT) has recently become commercially available, offering the opportunity to accurately image and target moving tumors as compared with computed tomography-guided radiation therapy (CTgRT) systems. However, the costs of delivering care with these 2 modalities remain poorly described. With localized unresectable hepatocellular carcinoma as an example, we were able to use time-driven activity-based costing to determine the cost of treatment on linear accelerators with CTgRT compared with MRgRT. MATERIALS AND METHODS: Process maps, informed via interviews with departmental personnel, were created for each phase of the care cycle. Stereotactic body radiation therapy was delivered at 50 Gy in 5 fractions, either with CTgRT using fiducial placement, deep inspiration breath-hold (DIBH) with real-time position management, and volumetric-modulated arc therapy, or with MRgRT using real-time tumor gating, DIBH, and static-gantry intensity-modulated radiation therapy. RESULTS: Direct clinical costs were $7,306 for CTgRT and $8,622 for MRgRT comprising personnel costs ($3,752 v $3,603), space and equipment costs ($2,912 v $4,769), and materials costs ($642 v $250). Increased MRgRT costs may be mitigated by forgoing CT simulation ($322 saved) or shortening treatment to 3 fractions ($1,815 saved). Conversely, adaptive treatment with MRgRT would result in an increase in cost of $529 per adaptive treatment. CONCLUSION: MRgRT offers real-time image guidance, avoidance of fiducial placement, and ability to use adaptive treatments; however, it is 18% more expensive than CTgRT under baseline assumptions. Future studies that elucidate the magnitude of potential clinical benefits of MRgRT are warranted to clarify the value of using this technology.