Seizure outcomes following single-fraction versus hypofractionated radiosurgery for brain metastases: a single-center experience.

OBJECTIVE: Although seizures are a relatively common phenomenon in the setting of brain metastases (BMs), there are no discrete recommendations regarding the use of antiepileptic drugs (AEDs) in this population, either in general or in the context of treatment. The authors' aim was to better understand the underlying pathological factors as well as the therapeutic techniques that may lead to seizures following the radiosurgical treatment of BMs with the goal of guiding appropriate AED prophylaxis. METHODS: Adult patients with BMs diagnosed from 2013 to 2020 at a single academic institution and treated with radiation therapy were included in this study. The authors evaluated factors associated with the incidence of seizures throughout the disease course, with a focus on seizures in the 90-day period following stereotactic radiosurgery (SRS). RESULTS: Four hundred forty-four patients with newly diagnosed BMs were identified, 10% of whom had seizures at the time of presentation and 28% of whom had a seizure at any point during the study period. Tumor histology was significantly associated with initial seizure risk. AED use was highly variable. In the 90-day post-SRS period, the summed total planning target volume (PTV) was independently predictive of post-SRS seizures, regardless of the fractionation scheme (single fraction vs hypofractionated) and other clinical factors. The number of supratentorial BMs was not predictive of post-SRS seizures. CONCLUSIONS: PTV is a superior predictor of post-SRS seizures relative to the number of supratentorial BMs, as it serves as a volumetric proxy for intracranial disease burden. A larger PTV, alongside tumor histology and prior seizure history, should be considered in the decision-making process for AED use following radiosurgery.

Retrospective examination of pseudoprogression in IDH mutant gliomas.

Background: Tumor surveillance of isocitrate dehydrogenase (IDH) mutant gliomas is accomplished via serial contrast MRI. When new contrast enhancement (CEnew) is detected during postsurgical surveillance, clinicians must assess whether CEnew indicates pseudoprogression (PsP) or tumor progression (TP). PsP has been better studied in IDH wild-type glioblastoma but has not been well characterized in IDH mutant gliomas. We conducted a retrospective study evaluating the incidence, predictors, natural history, and survival of PsP patients in a large cohort of IDH mutant glioma patients treated at a single institution. Methods: We identified 587 IDH mutant glioma patients treated at UCLA. We directly inspected MRI images and radiology reports to identify CEnew and categorized CEnew into TP or PsP using MRI or histopathology. Results: Fifty-six percent of patients developed CEnew (326/587); of these, 92/326 patients (28% of CEnew; 16% of all) developed PsP and 179/326 (55%) developed TP. All PsP patients had prior radiation, chemotherapy, or chemoradiotherapy. PsP was associated with longer overall survival (OS) versus TP patients and similar OS versus no CEnew. PsP differs from TP based on earlier time of onset (median 5.8 vs 17.4 months from treatment, P < .0001) and MRI features that include punctate enhancement and enhancement location. Conclusion: PsP patients represented 28% of CEnew patients and 16% of all patients; PsP patients demonstrated superior outcomes to TP patients, and equivalent survival to patients without CEnew. PsP persists for <1 year, occurs after treatment, and differs from TP based on time of onset and radiographic features. Poor outcomes after CEnew are driven by TP.

Experience of Telemedicine Visits in Radiation Oncology During the COVID-19 Pandemic: A US National Survey and Lessons Learned for Incorporating Telemedicine Post-COVID-19.

Purpose: We sought to survey the attitudes and perceptions of US radiation oncologists toward the adoption of telemedicine during the COVID-19 pandemic and offer suggestions for its integration in the postpandemic era. Methods and Materials: A 25-question, anonymous online survey was distributed nationwide to radiation oncologists. Results: One hundred and twenty-one respondents completed the survey, with 92% from academia. Overall, 79% worked at institutions that had implemented a work-from-home policy, with which 74% were satisfied. Despite nearly all visit types being conducted in-person before COVID-19, 25%, 41%, and 5% of the respondents used telemedicine for more than half of their new consultations, follow-up, and on-treatment visits, respectively, during the COVID-19 pandemic. Most (83%) reported being comfortable integrating telemedicine. Although telemedicine was appreciated as being more convenient for patients (97%) and reducing transmission of infectious agents (83%), the most commonly perceived disadvantages were difficulty in performing physical examinations (90%), patients' inability to use technology adequately (74%), and technical malfunctions (72%). Compared with in-person visits, telemedicine was felt to be inferior in establishing a personal connection during consultation (90%) and assessing for toxicity while on-treatment (88%) and during follow-up (70%). For follow-up visits, genitourinary and thoracic were perceived as most appropriate for telemedicine while gynecologic and head and neck were considered the least appropriate. Overall, 70% were in favor of more telemedicine, even after pandemic is over. Conclusions: Telemedicine will likely remain part of the radiation oncology workflow in most clinics after the pandemic. It should be used in conjunction with in-person visits, and may be best used for conducting follow-up visits in certain disease sites such as genitourinary and thoracic malignancies.

Relapse patterns and radiation dose exposure in IDH wild-type glioblastoma at first radiographic recurrence following chemoradiation.

PURPOSE: To quantify the radiation dose distribution and lesion morphometry (shape) at baseline, prior to chemoradiation, and at the time of radiographic recurrence in patients with glioblastoma (GBM). METHODS: The IMRT dose distribution, location of the center of mass, sphericity, and solidity of the contrast enhancing tumor at baseline and the time of tumor recurrence was quantified in 48 IDH wild-type GBM who underwent postoperative IMRT (2 Gy daily for total of 60 Gy) with concomitant and adjuvant temozolomide. RESULTS: Average radiation dose within enhancing tumor at baseline and recurrence was ≥ 60 Gy. Centroid location of the enhancing tumor shifted an average of 11.3 mm at the time of recurrence with respect to pre-IMRT location. A positive correlation was observed between change in centroid location and PFS in MGMT methylated patients (P = 0.0007) and Cox multivariate regression confirmed centroid distance from baseline was associated with PFS when accounting for clinical factors (P = 0.0189). Lesion solidity was higher at recurrence compared to baseline (P = 0.0118). Tumors that progressed > 12 weeks after IMRT were significantly more spherical (P = 0.0094). CONCLUSION: Most GBMs recur local within therapeutic IMRT doses; however, tumors with longer PFS occurred further from the original tumor location and were more solid and/or nodular.

Germline biomarkers predict toxicity to anti-PD1/PDL1 checkpoint therapy.

BACKGROUND: There is great interest in finding ways to identify patients who will develop toxicity to cancer therapies. This has become especially pressing in the era of immune therapy, where toxicity can be long-lasting and life-altering, and primarily comes in the form of immune-related adverse effects (irAEs). Treatment with the first drugs in this class, anti-programmed death 1 (anti-PD1)/programmed death-ligand 1 (PDL1) checkpoint therapies, results in grade 2 or higher irAEs in up to 25%-30% of patients, which occur most commonly within the first 6 months of treatment and can include arthralgias, rash, pruritus, pneumonitis, diarrhea and/or colitis, hepatitis, and endocrinopathies. We tested the hypothesis that germline microRNA pathway functional variants, known to predict altered systemic stress responses to cancer therapies, would predict irAEs in patients across cancer types. METHODS: MicroRNA pathway variants were evaluated for an association with grade 2 or higher toxicity using four classifiers on 62 patients with melanoma, and then the panel's performance was validated on 99 patients with other cancer types. Trained classifiers included classification trees, LASSO-regularized logistic regression, boosted trees, and random forests. Final performance measures were reported on the training set using leave-one-out cross validation and validated on held-out samples. The predicted probability of toxicity was evaluated for its association, if any, with response categories to anti-PD1/PDL1 therapy in the melanoma cohort. RESULTS: A biomarker panel was identified that predicts toxicity with 80% accuracy (F1=0.76, area under the curve (AUC)=0.82) in the melanoma training cohort and 77.6% accuracy (F1=0.621, AUC=0.778) in the pan-cancer validation cohort. In the melanoma cohort, the predictive probability of toxicity was not associated with response categories to anti-PD1/PDL1 therapy (p=0.70). In the same cohort, the most significant biomarker of toxicity in RAC1, predicting a greater than ninefold increased risk of toxicity (p<0.001), was also not associated with response to anti-PD1/PDL1 therapy (p=0.151). CONCLUSIONS: A germline microRNA-based biomarker signature predicts grade 2 and higher irAEs to anti-PD1/PDL1 therapy, regardless of tumor type, in a pan-cancer manner. These findings represent an important step toward personalizing checkpoint therapy, the use of which is growing rapidly.

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.

Voxelwise Prediction of Recurrent High-Grade Glioma via Proximity Estimation-Coupled Multidimensional Support Vector Machine.

PURPOSE: To provide early and localized glioblastoma (GBM) recurrence prediction, we introduce a novel postsurgery multiparametric magnetic resonance-based support vector machine (SVM) method coupling with stem cell niche (SCN) proximity estimation. METHODS AND MATERIALS: This study used postsurgery magnetic resonance imaging (MRI) scans from 50 patients with recurrent GBM, obtained approximately 2 months before clinically diagnosed recurrence. The main prediction pipeline consisted of a proximity-based estimator to identify regions with high risk of recurrence (HRRs) and an SVM classifier to provide voxelwise prediction in HRRs. The HRRs were estimated using the weighted sum of inverse distances to 2 possible origins of recurrence-the SCN and the tumor cavity. Subsequently, multiparametric voxels (from T1, T1 contrast-enhanced, fluid-attenuated inversion recovery, T2, and apparent diffusion coefficient) within the HRR were grouped into recurrent (warped from the clinical diagnosis) and nonrecurrent subregions and fed into the proximity estimation-coupled SVM classifier (SVMPE). The cohort was randomly divided into 40% and 60% for training and testing, respectively. The trained SVMPE was then extrapolated to an earlier time point for earlier recurrence prediction. As an exploratory analysis, the SVMPE predictive cluster sizes and the image intensities from the 5 magnetic resonance sequences were compared across time to assess the progressive subclinical traces. RESULTS: On 2-month prerecurrence MRI scans from 30 test cohort patients, the SVMPE classifier achieved a recall of 0.80, a precision of 0.69, an F1-score of 0.73, and a mean boundary distance of 7.49 mm. Exploratory analysis at early time points showed spatially consistent but significantly smaller subclinical clusters and significantly increased T1 contrast-enhanced and apparent diffusion coefficient values over time. CONCLUSIONS: We demonstrated a novel voxelwise early prediction method, SVMPE, for GBM recurrence based on clinical follow-up MR scans. The SVMPE is promising in localizing subclinical traces of recurrence 2 months ahead of clinical diagnosis and may be used to guide more effective personalized early salvage therapy.

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.

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.

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.

Treating Glioblastoma Multiforme (GBM) with super hyperfractionated radiation therapy: Implication of temporal dose fractionation optimization including cancer stem cell dynamics.

PURPOSE: A previously developed ordinary differential equation (ODE) that models the dynamic interaction and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC) was used to explain the definitive treatment failure in Glioblastoma Multiforme (GBM) for conventionally and hypo-fractionated treatments. In this study, optimization of temporal dose modulation based on the ODE equation is performed to explore the feasibility of improving GBM treatment outcome. METHODS: A non-convex optimization problem with the objective of minimizing the total cancer cell number while maintaining the normal tissue biological effective dose (BEDnormal) at 100 Gy, equivalent to the conventional 2 Gy × 30 dosing scheme was formulated. With specified total number of dose fractions and treatment duration, the optimization was performed using a paired simulated annealing algorithm with fractional doses delivered to the CSC and DCC compartments and time intervals between fractions as variables. The recurrence time, defined as the time point at which the total tumor cell number regrows to 2.8×109 cells, was used to evaluate optimization outcome. Optimization was performed for conventional treatment time frames equivalent to currently and historically utilized fractionation schemes, in which limited improvement in recurrence time delay was observed. The efficacy of a super hyperfractionated approach with a prolonged treatment duration of one year was therefore tested, with both fixed regular and optimized variable time intervals between dose fractions corresponding to total number of fractions equivalent to weekly, bi-weekly, and monthly deliveries (n = 53, 27, 13). Optimization corresponding to BEDnormal of 150 Gy was also obtained to evaluate the possibility in further recurrence delay with dose escalation. RESULTS: For the super hyperfractionated schedules with dose fraction number equivalent to weekly, bi-weekly, and monthly deliveries, the recurrence time points were found to be 430.5, 423.9, and 413.3 days, respectively, significantly delayed compared with the recurrence time of 250.3 days from conventional fractionation. Results show that optimal outcome was achieved by first delivering infrequent fractions followed by dense once per day fractions in the middle and end of the treatment course, with sparse and low dose treatments in the between. The dose to the CSC compartment was held relatively constant throughout while larger dose fractions to the DCC compartment were observed in the beginning and final fractions that preceded large time intervals. Dose escalation to BEDnormal of 150 Gy was shown capable of further delaying recurrence time to 452 days. CONCLUSION: The development and utilization of a temporal dose fractionation optimization framework in the context of CSC dynamics have demonstrated that substantial delay in GBM local tumor recurrence could be achieved with a super hyperfractionated treatment approach. Preclinical and clinical studies are needed to validate the efficacy of this novel treatment delivery method.

Quantitative Characterization of Tumor Proximity to Stem Cell Niches: Implications on Recurrence and Survival in GBM Patients.

PURPOSE: Emerging evidence has linked glioblastoma multiforme (GBM) recurrence and survival to stem cell niches (SCNs). However, the traditional tumor-ventricle distance is insufficiently powered for an accurate prediction. We aimed to use a novel inverse distance map for improved prediction. METHODS AND MATERIALS: Two T1-magnetic resonance imaging data sets were included for a total of 237 preoperative scans for prognostic stratification and 55 follow-up scans for recurrent pattern identification. SCN, including the subventricular zone (SVZ) and subgranular zone (SGZ), were manually defined on a standard template. A proximity map was generated using the summed inverse distances to all SCN voxels. The mean and maximum proximity scores (PSm-SCN and PSmax-SCN) were calculated for each primary/recurrent tumor, deformably transformed into the template. The prognostic capacity of proximity score (PS)-derived metrics was assessed using Cox regression and log-rank tests. To evaluate the impact of SCNs on recurrence patterns, we performed group comparisons of PS-derived metrics between the primary and recurrent tumors. For comparison, the same analyses were conducted on PS derived from SVZ alone and traditional edge/center-to-ventricle metrics. RESULTS: Among all SCN-derived features, PSm-SCN was the strongest survival predictor (P < .0001). PSmax-SCN was the best in risk stratification, using either evenly sorted (P = .0001) or k-means clustering methods (P = .0045). PS metrics based on SVZ only also correlated with overall survival and risk stratification, but to a lesser degree of significance. In contrast, edge/center-to-ventricle metrics showed weak to no prediction capacities in either task. Moreover, PSm-SCN,PSm-SVZ, and center-to-ventricle metrics revealed a significantly closer SCN distribution of recurrence than primary tumors. CONCLUSIONS: We introduced a novel inverse distance-based metric to comprehensively capture the anatomic relationship between GBM tumors and SCN zones. The derived metrics outperformed traditional edge or center distance-based measurements in overall survival prediction, risk stratification, and recurrent pattern differentiation. Our results reveal the potential role of SGZ in recurrence aside from SVZ.

A Practical Guide for Navigating the Design, Build, and Clinical Integration of Electronic Patient-Reported Outcomes in the Radiation Oncology Department.

The development and integration of electronic patient-reported outcomes (ePROs) into the radiation oncology clinic workflow provide novel opportunities, accompanied by unique design considerations and implementation challenges. The processes required for implementation of ePROs are entirely distinct from standard paper-based surveys, with the majority of time devoted to conception and design before initiating questionnaire build, detailed workflow process mapping including development of new workflows, comprehensive communication of the vision between providers and the information technology team, and quality assurance. Based on our experience with implementation of ePROs in our radiation oncology department, we developed a stepwise framework for approaching ePRO conceptual design, build, workflow integration, and the electronic health record interface. Here, we provide a guide for the numerous considerations, decision points, and solutions associated with the implementation of ePROs in the radiation oncology department setting. Although various ePRO tools and electronic health record capabilities impose different requirements, opportunities, and limitations, the conceptual processes and many of the electronic build considerations are broadly applicable.

Time-Driven Activity-Based Costing Analysis of Telemedicine Services in Radiation Oncology.

PURPOSE: Health systems have increased telemedicine use during the SARS-CoV-2 outbreak to limit in-person contact. We used time-driven activity-based costing to evaluate the change in resource use associated with transitioning to telemedicine in a radiation oncology department. METHODS AND MATERIALS: Using a patient undergoing 28-fraction treatment as an example, process maps for traditional in-person and telemedicine-based workflows consisting of discrete steps were created. Physicians/physicists/dosimetrists and nurses were assumed to work remotely 3 days and 1 day per week, respectively. Mapping was informed by interviews and surveys of personnel, with cost estimates obtained from the department's financial officer. RESULTS: Transitioning to telemedicine reduced provider costs by $586 compared with traditional workflow: $47 at consultation, $280 during treatment planning, $237 during on-treatment visits, and $22 during the follow-up visit. Overall, cost savings were $347 for space/equipment and $239 for personnel. From an employee perspective, the total amount saved each year by not commuting was $36,718 for physicians (7243 minutes), $19,380 for physicists (7243 minutes), $17,286 for dosimetrists (7210 minutes), and $5599 for nurses (2249 minutes). Patients saved $170 per treatment course. CONCLUSIONS: A modified workflow incorporating telemedicine visits and work-from-home capability conferred savings to a department as well as significant time and costs to health care workers and patients alike.

Targeted Radiation Therapy Can Treat Myxomatous Cerebral Aneurysms.

BACKGROUND: Neoplastic cerebral aneurysms are rare presentations of cardiac myxomas. The natural history of such aneurysms is not well understood, and the optimal treatment strategy remains unclear. Clipping and coiling are effective, although can carry significant morbidity. Chemotherapy and radiation can theoretically be effective, although their clinical efficacy remains to be proven. CASE DESCRIPTION: Here we describe a patient with cardiac myxoma presenting with multiple progressively fusiform aneurysms. These aneurysms were noted to be growing during conservative monitoring given the eloquent location. Subsequently, the patient underwent multiple sessions of targeted radiation therapy, which lead to obliteration, shrinkage, or halting in growth of these aneurysms. CONCLUSIONS: Low-dose targeted radiation therapy can be safe and effective in treatment of neoplastic myxomatous aneurysms.

Time-Driven Activity-Based Costing Comparison of Stereotactic Radiosurgery to Multiple Brain Lesions Using Single-Isocenter Versus Multiple-Isocenter Technique.

PURPOSE: Stereotactic radiosurgery (SRS) historically has been used to treat multiple brain lesions using a multiple-isocenter technique-frequently associated with significant complexity in treatment planning and long treatment times. Recently, given innovations in planning algorithms, patients with multiple brain lesions may now be treated with a single-isocenter technique using fewer total arcs and less time spent during image guidance (though with stricter image guided radiation therapy tolerances). This study used time-driven activity-based costing to determine the difference in cost to a provider for delivering SRS to multiple brain lesions using single-isocenter versus multiple-isocenter techniques. METHODS AND MATERIALS: Process maps, consisting of discrete steps, were created for each phase of the SRS care cycle and were based on interviews with department personnel. Actual treatment times (including image guidance) were extracted from treatment record and verify software. Additional sources of data to determine costs included salary/benefit data of personnel and average list price/maintenance costs for equipment. RESULTS: Data were collected for 22 patients who underwent single-isocenter SRS (mean lesions treated, 5.2; mean treatment time, 30.2 minutes) and 51 patients who underwent multiple-isocenter SRS (mean lesions treated, 4.4; mean treatment time, 75.2 minutes). Treatment time for multiple-isocenter SRS varied substantially with increasing number of lesions (11.8 minutes/lesion; P < .001), but to a much lesser degree in single-isocenter SRS (1.8 minutes/lesion; P = .029). The resulting cost savings from single-isocenter SRS based on number of lesions treated ranged from $296 to $3878 for 2 to 10 lesions treated. The 2-mm planning treatment volume margin used with single-isocenter SRS resulted in a mean 43% increase of total volume treated compared with a 1-mm planning treatment volume expansion. CONCLUSIONS: In a comparison of time-driven activity-based costing assessment of single-isocenter versus multiple-isocenter SRS for multiple brain lesions, single-isocenter SRS appears to save time and resources for as few as 2 lesions, with incremental benefits for additional lesions treated.

Diffusion MRI changes in the anterior subventricular zone following chemoradiation in glioblastoma with posterior ventricular involvement.

INTRODUCTION: There is growing evidence that the subventricular zone (SVZ) plays a key role in glioblastoma (GBM) tumorigenesis. However, little is known regarding how the SVZ, which is a harbor for adult neural stem cells, may be influenced by chemoradiation. The current diffusion-weighted imaging (DWI) study explored ipsilateral and contralateral alterations in the anterior SVZ in GBM patients with posterior enhancing lesions following chemoradiation. METHODS: Forty GBM patients with tumor involvement in the posterior SVZ (mean age = 57 ± 10; left-hemisphere N = 25; right-hemisphere N = 15) were evaluated using DWI before and after chemoradiation. Regions-of-interest were drawn on the ipsilesional and contralesional anterior SVZ on apparent diffusion coefficient (ADC) maps for both timepoints. ADC histogram analysis was performed by modeling a bimodal, double Gaussian distribution to obtain ADCL, defined as the mean of the lower Gaussian distribution. RESULTS: The ipsilesional SVZ had lower ADCL values compared to the contralesional SVZ before treatment (mean difference = 0.025 µm2/ms; P = 0.007). Following chemoradiation, these changes were no longer observed (mean difference = 0.0025 µm2/ms; P > 0.5), as ADCL values of the ipsilesional SVZ increased (mean difference = 0.026 µm2/ms; P = 0.037). An increase in ipsilesional ADCL was associated with shorter progression-free (P = 0.0119) and overall survival (P = 0.0265). CONCLUSIONS: These preliminary observations suggest baseline asymmetry as well as asymmetric changes in the SVZ proximal (ipsilesional) to the tumor with respect to contralesional SVZ regions may be present in GBM, potentially implicating this region in tumorigenesis and/or treatment resistance.

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.