PURPOSE:Radiosurgical treatment of multiple intracranial targets using a single isocenter is more efficient than sequential isocenter treatment. The primary concern with single-isocenter, multitarget (SIMT) stereotactic radiosurgery (SRS) is that rotational error may cause underdosing of peripheral lesions and/or increased normal tissue toxicity, particularly for targets distant from the isocenter. Many centers mitigate this risk by adding a planning target volume (PTV) margin, which increases dose to normal brain tissue. This study examined whether distance from the isocenter affects local tumor control or toxicity in patients treated with SIMT SRS using a 0-mm PTV margin. METHODS AND MATERIALS:We retrospectively evaluated 429 patients with 3039 intracranial tumors treated with SIMT SRS or fractionated SRS using single-isocenter volumetric modulated arc therapy plans with a 0-mm clinical target volume/PTV expansion from gross tumor volume. All treatments used the Varian HD-120 multileaf collimators on a 6-degree-of-freedom couch. Local failure was defined as ≥25% increase in maximum tumor diameter (minimum 3 mm) or viable tumor cells at salvage surgery. Toxicity was defined as National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 central nervous system grade ≥3. RESULTS:Of the 3039 tumors evaluated, 1510 and 1034 tumors had clinical and radiographic follow-up at 6 months and 1 year, respectively. Median distance from the isocenter was 4.9 cm (range, 0.04-13.4 cm) and 70% of tumors in this study were ≥4 cm from the isocenter. One-year local control was 95.1% (95% CI, 94.0-96.1) and freedom from grade ≥3 toxicity was 98.4% (95% CI, 97.8-99.0). Larger tumor volume correlated with both worse local control (hazard ratio, 1.017; 95% CI, 1.000-1.034; P = .047) and higher toxicity (hazard ratio, 1.088; 95% CI, 1.056-1.121; P < .001). Increased distance from the isocenter was not associated with worse local failure or toxicity on multivariable analysis. CONCLUSIONS:In this retrospective analysis of SIMT volumetric modulated arc therapy radiosurgery using HD-120 multileaf collimators, 6-degree-of-freedom couch, intrafraction surface monitoring, and 0-mm clinical target volume/PTV margin, increased distance from the isocenter did not adversely impact short-term local tumor control or increase high-grade toxicity. These findings are currently being tested in a prospective randomized trial.

Background:Brain metastases (BMs) patients often receive multiple courses of radiotherapy (RT). Comparing follow-up imaging with RT plans is time-intensive and currently not possible in picture archiving and communication system (PACS). In this study, we aim to develop an automated tool to overlay pre-RT tumor contours onto follow-up MRI in the PACS to support response assessment and identification of untreated metastases, reducing review complexity and time. Methods:We built an AI-driven workflow that registers planning CT to follow-up MRI and propagates treated-lesion contours; outputs are exported as PACS-compliant DICOM. Performance was evaluated in 40 patients: 20 underwent quantitative comparison between manual and automated registrations using Dice similarity coefficient (DSC) and mean surface distance (MSD), following AAPM TG-132 guidelines; 20 additional patients (5-35 lesions per patient) underwent clinical evaluation of follow-up and pre-RT lesions contours visualization in PACS. Three physicians assessed these cases to measure review time and inter-observer agreement in treatment response classification (improved/stable vs indeterminate). Results:The workflow successfully registered all CT-MRI pairs. Mean DSC/MSD was: brain 0.97 ± 0.01/0.0 ± 0.0 mm, brainstem 0.89 ± 0.03/0.1 ± 0.1 mm, and gross tumor volumes 0.65 ± 0.18/0.6 ± 0.4 mm. Average physician review time per case decreased from 7.97 to 3.95 min with the automated workflow, and full inter-physician agreement increased from 72.4% to 93.5%. Conclusion:We developed and validated an AI-based tool that accurately fuses pre-RT contours with follow-up MRI for BMs, addressing a key gap in current PACS systems. The workflow significantly reduced review time per lesion and enhanced inter-physician agreement, and has the potential to enable faster, more consistent multidisciplinary follow-up assessment.

PURPOSE:Survival for patients with melanoma has recently improved. The propensity of melanoma to metastasize to the brain remains a common and serious feature of this disease. The purposes of this study were to evaluate prognostic factors for patients with newly diagnosed melanoma brain metastases (MBMs) in a large cohort treated with modern multimodal therapies, compare those results with those in prior eras, and update the Melanoma Graded Prognostic Assessment (GPA). METHODS:Univariable and multivariable (MVA) analyses of prognostic factors and treatments associated with survival were performed on 1,796 patients with newly diagnosed MBM treated between January 01, 2015, and December 31, 2021, using a multi-institutional retrospective database. Multiple imputation was used to address missingness of potential predictors. Significant variables in combined MVA were used to update the Melanoma GPA. Comparisons were made with legacy cohorts. RESULTS:Median survivals for cohorts A (1985-2007, n = 481), B (2006-2015, n = 823), and C (2015-2021, n = 1,796) were 6.7, 9.8, and 16.6 months and median follow-up times were 40.1, 43.6, and 48.8 months, respectively. In combined MVA, significant prognostic factors for survival were higher Karnofsky Performance Status, fewer MBMs, absence of extracranial metastases, lower serum lactate dehydrogenase, and no immunotherapy before MBM. These factors were incorporated into the updated Melanoma GPA. The combined median and 3-year survivals for patients with GPA 0-1, 1.5-2, and 2.5-4.0 were 5.4, 13.2, and 43.2 months and 12.4%, 28.8%, and 51.6%, respectively. CONCLUSION:Prognostic factors have changed and survival has improved for patients with MBM but varies widely by GPA. The updated Melanoma GPA calculator (BrainMetGPA), available free online, can be used to estimate survival, individualize treatment, stratify clinical trials, guide surveillance, and augment clinical trial eligibility. Multidisciplinary treatment is essential. Trials are needed to elucidate the optimal sequencing of various therapeutic modalities.

Purpose:Single isocenter stereotactic radiosurgery (SRS) efficiently delivers radiation to patients with multiple brain metastases. Although several fractionated SRS (fSRS) regimens show acceptable local control and toxicity, few studies directly compare them. This retrospective study evaluates 2 common regimens-6 Gy × 5 fractions and 9 Gy × 3 fractions-for their effects on local control and toxicity. Methods and Materials:A retrospective review was conducted of 1215 brain tumors from 251 patients receiving either 9 Gy × 3 fx or 6 Gy × 5 fx fSRS. All tumors were treated with single isocenter volumetric modulated arc therapy. Recurrent tumors and postoperative cavities were excluded from the analysis. Local tumor failure was defined as 25% increase in maximum tumor diameter (minimum 3 mm) or more than scant tumor cells at time of salvage surgery. Toxicity included CTCAE V5.0 central nervous system (CNS) grade 3 or greater events. Local tumor control and freedom from toxicity were calculated using Kaplan-Meier method and Cox regression models. Results:Overall local control was 93% at 1 year and 88% at 2 years. The 3-fraction regimen had superior 1-year local control compared with the 5-fraction regimen (97% vs. 91%, P = .001). Tumors <2 cm had significantly better control with 3 fractions (99% vs. 95%, P = .004), whereas tumors 2-4 cm showed no significant difference. One-year freedom from grade 3+ toxicity was similar between regimens (99% for 3-fx vs. 96% for 5-fx, P = .097). Conclusions:In this study, 9 Gy × 3 fx for brain metastases had improved tumor control and comparable toxicity to 6 Gy × 5, particularly among tumors <2 cm. 9 Gy × 3 fx may be the preferred regimen when treating multiple tumors with one prescription using single isocenter radiosurgery as it improves efficiency and local control while having similar toxicity.

Purpose: Online adaptive radiation therapy (oART) has shown the ability to diminish interfraction variations. However, oART is a time- and labor-intensive process, and the optimal adaptation frequency remains to be determined for lung cancer oART. The purpose of this study was to quantify and assess dosimetric benefits associated with various adaptive frequencies in patients with lung cancer receiving oART. Methods and Materials: This study included 8 patients with lung cancer receiving oART treated on the Ethos platform in 30 or 33 fractions (n = 7 /1). For a total of 243 fractions, daily contours on cone-beam computed tomography (CT) and adaptive/nonadaptive plans on synthetic CT scan were used to simulate 4 different adaptation frequencies: none, single, weekly, and daily adaptation, resulting in 972 unique dose distributions. Dose-volume-histograms of targets and organs-at-risk (OARs) were compared between adaptation frequencies. Besides Dose-volume-histogram analysis, 3 radiation oncologists reviewed and scored 185 total plans, evenly sampling plans from the various adaptive frequencies. A comprehensive plan scorecard was fine-tuned to correlate with physician reviews and subsequently used for interplan comparison. Results: Compared with no adaptation, daily adaptation improved the median clinical target volume V100% by 0.2% (IQR, 0.0-1.0) and the planning target volume D98% by 0.5% (IQR, 2.2 to 3.83). It also reduced the planning target volume D0.03cc by 2.1% (IQR, 0.7-3.2), the lungs-internal target volume V20 Gy by 2.5% (IQR, 1.0-4.5), the heart Dmean by 0.9 Gy (IQR, 0.4-2.6), and the esophagus Dmean by 1.6 Gy (IQR, 0.3-4.3). Single and weekly adaptation presented fewer benefits in OAR sparing and led to target undercoverage compared with daily adaptation. The PlanScoreCard effectively quantified plan quality, showing a positive monotonic correlation to physician scores (R = 0.57-0.87). It revealed that daily adaptation significantly improved total plan quality for 7 out of 8 patients, with improvements exceeding 5% of the plan score compared with no adaptation. In contrast, weekly and single adaptations led to improvements in only 2 and 1 patients, respectively. Conclusions: Online kilovoltage cone-beam CT scan-guided daily adaptation may lead to dosimetric benefits in both target coverage and OAR sparing in patients with lung cancer. Other adaptation frequencies are effective for some patients but tend to lead to target undercoverage compared with daily adaptation. (c) 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Purpose/Objective(s) Cone-beam computed tomography (CBCT)-guided online adaptive radiotherapy (oART) has shown benefits for lung cancer patients, yet the optimal adaptation frequency for oART remains unclear. We hypothesized that the magnitude of benefit from oART correlates with the frequency of adaptation and is patient-dependent for conventionally-fractionated lung cancer treatment. Materials/Methods Eight lung cancer patients treated with daily CBCT-guided oART in 30/33 fractions (n = 7/1) were included in this study. For a total of 243 fractions, daily contours on CBCT and adaptive/non-adaptive plans on synthetic CT (sCT) were used to simulate four different adaptation frequencies: (1) no adaptation; (2) single adaptation (replanning at fraction 21); (3) weekly adaptation (adapted plan used remainder of week); (4) daily adaptation. Dose volume histograms (DVH) from each treatment fraction were compared between adaptation frequencies, and each plan was compared. Patient-specific analysis of different adaptation frequencies was conducted using an open-source PlanScoreCard tool, which quantifies individual plan quality by equally weighting target and OAR dosimetry (50% each). To evaluate the accuracy with which the PlanScoreCard reflected plan quality, three attending radiation oncologists performed manual review of a subset of patients’ plans using a five-point Likert scale. Results Across 972 plans, daily-adaptation significant improved (p≤0.01, Wilcoxon paired test) clinical target volume (CTV) V100%, planning target volume (PTV) D98%, PTV D0.03cc, PTV homogeneity index, lungs-gross tumor volume (GTV) V20%, heart Dmean, and esophagus Dmean, as compared to all other adaptation strategies. Compared to no adaptation, daily adaptation led to mean [range] plan score increase of 12.5% [1.7-29.3%], substantially benefiting 6/8 patients (improvement ≥5.0%). Weekly adaption achieved an increase of 3.3% [-0.9-12.5%], with 3/8 patients receiving nominal benefits. Single-adaptation only showed a mean score increase of 0.5% [-3.6 – 3.3%]. Plan scores showed strong monotonic correlation with Likert ratings (Spearman correlation (R) = [0.67-0.82]). Conclusion Physician reviews indicated that an in-house scorecard was adept at measuring increasing plan quality with adaption frequency. Only daily adaptation consistently achieved initial plan quality and showed improvements compared to no adaptation, while the effectiveness of other adaptation frequencies varied and was patient-dependent.

This study explores the dosimetric benefits of cone-beam computed tomography (CBCT)-based online adaptive radiation therapy (oART) for a non-small-cell lung cancer (NSCLC) patient exhibiting significant tumor shrinkage during ChemoRT. The patient was prescribed 60 Gray (Gy) in 30 fractions and was initially treated with conventional RT. After the delivery of the first four treatment fractions, the patient's treatment course was converted to oART due to tumor shrinkage seen on CBCT. Current oART dose calculations use a synthetic CT (sCT) image derived from deformable image registration (DIR) of the planning CT to the daily CBCT, and, as the tumor regressed, the discrepancy between the CBCT and the sCT increased, leading to a re-simulation after the delivery of the ninth fraction. In this case report, we first investigated dosimetric differences leveraged by converting this patient from conventional RT to oART. With oART using sCT, the patient's target coverage remained consistent with the reference plan while simultaneously changing lung V20 by 7.8 ± 1.4% and heart mean by 3.4 ± 1.5 Gy. Then, using this new simulation CT and comparing it with iterative CBCT (iCBCT) images acquired with the new HyperSight™ (HS) (Varian Medical Systems, Inc., Palo Alto, CA, USA) imaging system on the Ethos, we investigated the impact of direct dose calculation on HS-iCBCT as compared to sCT. The HS-iCBCT generated a dose distribution similar to the CT reference, achieving a 96.01% gamma passing rate using Task Group-218 (TG-218) criteria. Results indicate that HS-iCBCT has the potential to better reflect daily anatomical changes, resulting in improved dosimetric accuracy. This study highlights the advantages of oART in the presence of tumor response to therapy and underscores HS-iCBCT's potential to provide CT-level dose calculation accuracy in oART for NSCLC patients.

Objective. Online adaptive radiotherapy (OART) is a promising technique for delivering stereotactic accelerated partial breast irradiation (APBI), as lumpectomy cavities vary in location and size between simulation and treatment. However, OART is resource-intensive, increasing planning and treatment times and decreasing machine throughput compared to the standard of care (SOC). Thus, it is pertinent to identify high-yield OART candidates to best allocate resources. Approach. Reference plans (plans based on simulation anatomy), SOC plans (reference plans recalculated onto daily anatomy), and daily adaptive plans were analyzed for 31 sequential APBI targets, resulting in the analysis of 333 treatment plans. Spearman correlations between 22 reference plan metrics and 10 adaptive benefits, defined as the difference between mean SOC and delivered metrics, were analyzed to select a univariate predictor of OART benefit. A multivariate logistic regression model was then trained to stratify high- and low-benefit candidates. Main results. Adaptively delivered plans showed dosimetric benefit as compared to SOC plans for most plan metrics, although the degree of adaptive benefit varied per patient. The univariate model showed high likelihood for dosimetric adaptive benefit when the reference plan ipsilateral breast V15Gy exceeds 23.5%. Recursive feature elimination identified 5 metrics that predict high-dosimetric-benefit adaptive patients. Using leave-one-out cross validation, the univariate and multivariate models classified targets with 74.2% and 83.9% accuracy, resulting in improvement in per-fraction adaptive benefit between targets identified as high- and low-yield for 7/10 and 8/10 plan metrics, respectively. Significance. This retrospective, exploratory study demonstrated that dosimetric benefit can be predicted using only ipsilateral breast V15Gy on the reference treatment plan, allowing for a simple, interpretable model. Using multivariate logistic regression for adaptive benefit prediction led to increased accuracy at the cost of a more complicated model. This work presents a methodology for clinics wishing to triage OART resource allocation.

Purpose: Accelerated partial breast irradiation (APBI) is an attractive treatment modality for eligible patients as it has been shown to result in similar local control and improved cosmetic outcomes compared with whole breast radiation therapy. The use of online adaptive radiation therapy (OART) for APBI is promising as it allows for a reduction of planning target volume margins because breast motion and lumpectomy cavity volume changes are accounted for in daily imaging. Here we present a retrospective, single-institution evaluation on the adequacy of kV-cone beam computed tomography (CBCT) OART for APBI treatments. Methods and Materials: Nineteen patients (21 treatment sites) were treated to 30 Gy in 5 fractions between January of 2022 and May of 2023. Time between simulation and treatment, change in gross tumor (ie, lumpectomy cavity) volume, and differences in dose volume histogram metrics with adaption were analyzed. The Wilcoxon paired, nonparametric test was used to test for dose volume histogram metric differences between the scheduled plans (initial plans recalculated on daily CBCT anatomy) and delivered plans, either the scheduled or adapted plan, which was reoptimized using daily anatomy. Results: Median (interquartile range) time from simulation to first treatment was 26 days (21-32 days). During this same time, median gross tumor volume reduction was 16.0% (7.3%-23.9%) relative to simulation volume. Adaptive treatments took 31.3 minutes (27.4-36.6 minutes) from start of CBCT to treatment session end. At treatment, the adaptive plan was selected for 86% (89/103) of evaluable fractions. In evaluating plan quality, 78% of delivered plans met all target, organs at risk, and conformity metrics evaluated, compared with 34% of scheduled plans. Conclusions: Use of OART for stereotactic linac-based APBI allowed for safe, high-quality treatments in this cohort of 21 treatment courses. Although treatment delivery times were longer than traditional stereotactic body treatments, there were notable improvements in plan quality for APBI using OART.

Purpose: The aim of this work was to describe the design and implementation of a more robust workflow for communicating outcomes from a peer-review chart rounds conference. We also provide information regarding cycle times, plan revisions, and other key metrics that we have observed since initial implementation. Methods and Materials: A multidisciplinary team of stakeholders including physicians, physicists, and dosimetrists developed a revised peer-review workflow that addressed key needs to improve the prior process. Consensus terminology was developed to reduce ambiguity regarding the priority of peer-review outcomes and to clarify expectations of the treating physician in response to peer-review outcomes. A custom workflow software tool was developed to facilitate both upstream and downstream processes from the chart rounds conference. The peer-review outcomes of the chart rounds conference and resulting plan changes for the first 18 months of implementation were summarized. Results: In the first 18 months after implementation of the revised processes, 2294 plans were reviewed, and feedback priority levels assigned. Across all cases with feedback, the median time for the treating attending physician to acknowledge conference comments was 1 day and was within 7 calendar days for 89.1% of cases. Conference feedback was acknowledged within 1 day for 74 of 115 (64.3%) cases with level 2 comments and for 18 of 21 (85.7%) cases with level 3 comments (P = .054). Contours were modified in 13 of 116 (11%) cases receiving level 2 feedback and 10 of 21 (48%) cases receiving level 3 feedback (P < .001). The treatment plan was revised in 18 of 116 (16%) cases receiving level 2 feedback and 13 of 21 (61%) cases receiving level 3 feedback (P < .001). Conclusions: We successfully implemented a workflow to improve upstream and downstream processes for a chart rounds conference. Standardizing how peer-review outcomes were communicated and recording physician responses allow for improved ability to monitor conference activities. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

APBI using oART decreased most organs at risk DVH metrics, improved plan quality metrics, and increased target coverage, justifying the use of kV-CBCT-guided oART for APBI.

BackgroundAccelerated partial breast irradiation (APBI) yields similar rates of recurrence and cosmetic outcomes as compared to whole breast radiation therapy (RT) when patients and treatment techniques are appropriately selected. APBI combined with stereotactic body radiation therapy (SBRT) is a promising technique for precisely delivering high levels of radiation while avoiding uninvolved breast tissue. Here we investigate the feasibility of automatically generating high quality APBI plans in the Ethos adaptive workspace with a specific emphasis on sparing the heart.MethodsNine patients (10 target volumes) were utilized to iteratively tune an Ethos APBI planning template for automatic plan generation. Twenty patients previously treated on a TrueBeam Edge accelerator were then automatically replanned using this template without manual intervention or reoptimization. The unbiased validation cohort Ethos plans were benchmarked via adherence to planning objectives, a comparison of DVH and quality indices against the clinical Edge plans, and qualitative reviews by two board-certified radiation oncologists.Results85% (17/20) of automated validation cohort plans met all planning objectives; three plans did not achieve the contralateral lung V1.5Gy objective, but all other objectives were achieved. Compared to the Eclipse generated plans, the proposed Ethos template generated plans with greater evaluation planning target volume (PTV_Eval) V100% coverage (p = 0.01), significantly decreased heart V1.5Gy (p< 0.001), and increased contralateral breast V5Gy, skin D0.01cc, and RTOG conformity index (p = 0.03, p = 0.03, and p = 0.01, respectively). However, only the reduction in heart dose was significant after correcting for multiple testing. Physicist-selected plans were deemed clinically acceptable without modification for 75% and 90% of plans by physicians A and B, respectively. Physicians A and B scored at least one automatically generated plan as clinically acceptable for 100% and 95% of planning intents, respectively.ConclusionsStandard left- and right-sided planning templates automatically generated APBI plans of comparable quality to manually generated plans treated on a stereotactic linear accelerator, with a significant reduction in heart dose compared to Eclipse generated plans. The methods presented in this work elucidate an approach for generating automated, cardiac-sparing APBI treatment plans for daily adaptive RT with high efficiency.

oART for APBI using SBRT for patients with ESBC is clinically feasible and allows for variations in lumpectomy cavity size. Nearly half of patients had no complaints or breast changes at one-month follow-up and the remaining had CTCAE grade 1 toxicities alone.

This study demonstrates that a small and carefully curated dataset can train an autocontouring model that is subjectively useful, time efficient, and objectively accurate. Future studies using the RADCOMP Atlas may benefit from autocontouring to standardize treatment or streamline central verification of treatment planning.

PurposeOnline Adaptive Radiation Therapy (oART) follows a different treatment paradigm than conventional radiotherapy, and because of this, the resources, implementation, and workflows needed are unique. The purpose of this report is to outline our institution's experience establishing, organizing, and implementing an oART program using the Ethos therapy system. MethodsWe include resources used, operational models utilized, program creation timelines, and our institutional experiences with the implementation and operation of an oART program. Additionally, we provide a detailed summary of our first year's clinical experience where we delivered over 1000 daily adaptive fractions. For all treatments, the different stages of online adaption, primary patient set-up, initial kV-CBCT acquisition, contouring review and edit of influencer structures, target review and edits, plan evaluation and selection, Mobius3D 2nd check and adaptive QA, 2nd kV-CBCT for positional verification, treatment delivery, and patient leaving the room, were analyzed. ResultsWe retrospectively analyzed data from 97 patients treated from August 2021-August 2022. One thousand six hundred seventy seven individual fractions were treated and analyzed, 632(38%) were non-adaptive and 1045(62%) were adaptive. Seventy four of the 97 patients (76%) were treated with standard fractionation and 23 (24%) received stereotactic treatments. For the adaptive treatments, the generated adaptive plan was selected in 92% of treatments. On average(+/- std), adaptive sessions took 34.52 +/- 11.42 min from start to finish. The entire adaptive process (from start of contour generation to verification CBCT), performed by the physicist (and physician on select days), was 19.84 +/- 8.21 min. ConclusionWe present our institution's experience commissioning an oART program using the Ethos therapy system. It took us 12 months from project inception to the treatment of our first patient and 12 months to treat 1000 adaptive fractions. Retrospective analysis of delivered fractions showed that the average overall treatment time was approximately 35 min and the average time for the adaptive component of treatment was approximately 20 min.

Purpose/Objective(s)This study reviews a treatment planning system (TPS) that automates both treatment planning and delivery of single-isocenter VMAT radiosurgery (SRS). The TPS was intended for complex multi-metastasis cases, for which it generates high quality, rapidly-deliverable plans. The effectiveness of treating benign intracranial pathologies (BIP) with TPS was unknown. Under an IRB-approved prospective registry, we collected data on the treatment planning and delivery as well as clinical outcomes of BIP managed with SRS since deployment of TPS.Materials/MethodsPatients included received SRS between October 2017 and November 2021 using TPS. Patients with less than 3 months follow-up (FU) were censored. For all targets, full prescription dose was normalized to ≥ 99% of target volume without additional PTV expansion. All treatments were delivered on a linear accelerator with 10MV flattening-filter free beam at 2400 MU/min with high-definition (2.5mm) multi-leaf collimator. Descriptive statistics related to SRS treatment, pathology, and prior therapy determined at the time of or prior to treatment were analyzed. Post-treatment imaging, toxicities, and standard pathology-specific outcomes were assessed during FU visits. Significant toxicity was defined as ≥ Grade 3 by CTCAE.Results245 targets (min=0.1cc, max=58.9cc) in 235 patients (53.5% female, median age=59) were treated with TPS. The most common pathologies were meningiomas (134), AVMs (43), pituitary adenomas (30), and acoustic schwannomas (23). 45% of patients were treated due to recurrent, residual, or persistent disease after prior treatment with 15% having prior radiation. A majority (53.5%) were treated in a single fraction (12-22Gy), and 46.5% were treated with fractionated SRS (24-35Gy). A majority (74%) were treated with 3 arcs with median (MED) total treatment and beam-on time lasting 10.4 and 2.3 minutes, respectively. MED RTOG CI and Paddick GI were 1.12 and 3.28, respectively. MED FU was 1.1 years. Excluding AVMs, 11 of 202 (5.4%) benign tumors progressed on FU imaging. Among those that progressed, MED time to failure was 1.14 years. Of those, 9 were WHO grade 2+ meningiomas with prior surgery. Of all patients, significant CNS toxicity was reported in 13 (5.6%, G3=9, G4=4), most of whom had persistent cerebral edema after steroids. Of those with BIP near cochlea (> 3 Gy dose max) without severe hearing loss prior to SRS (n=65), 14% subjectively reported decreased hearing after SRS and 3.5% did not preserve hearing. Of those with BIP near the optics (> 3 Gy dose max, n=81), visual preservation was 100%.ConclusionAlthough developed for multi-metastasis SRS, TPS is capable of generating and efficiently delivering high quality plans characterized by excellent conformality and rapid fall-off. Early clinical outcomes appear congruent with historical controls.

Brain metastases cause significant morbidity and mortality in patients with advanced cancer. In the era of precision oncology and immunotherapy, there are rapidly evolving systemic treatment options. These novel therapies may have variable intracranial efficacy, and patients with brain metastases remain a population of special interest. Typically, only patients with stable, asymptomatic and/or treated brain metastases are enrolled in clinical trials, or may be excluded altogether, particularly in the setting of leptomeningeal carcinomatosis. Consequently, this leads to significant concerns on the external validity of clinical trial evidence to real-world clinical practice. Here we describe the current trends in cancer clinical trial eligibility for patients with brain metastases in both early and late phase trials, with a focus on targeted and immunotherapies. We evaluate recent newly FDA approved therapies and the clinical trial evidence base leading to approval. This includes analysis of inclusion and exclusion criteria, requirements for baseline screening for brain metastases, surveillance cerebral imaging and incorporation of trial endpoints for patients with brain metastases. Finally, the use of alternative sources of data such as real-world evidence with registries and collaborative studies will be discussed.

Background: For early stage breast cancer, breast conservation is an appealing option for many women. Interest in reducing the duration and volume of RT has continued in the form of accelerated partial breast irradiation (APBI). Recent work demonstrates that for appropriately selected patients, APBI yields equivalent rates of ipsilateral breast tumor recurrence (IBTR) with improvements in patient rated cosmesis compared to whole breast radiotherapy. When using external beam radiotherapy for APBI, appropriate techniques to reduce setup uncertainty and overall treatment volume are critical to reduce long term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is an attractive technique to deliver APBI because of its excellent accuracy and potentially superior sparing of uninvolved breast tissue. We report here the initial results of our IRB-approved prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of daily, 5-fraction SBRT for APBI in women meeting ASTRO consensus suitability criteria for partial breast irradiation. Methods: We enrolled twenty patients with early stage breast cancer after lumpectomy who met APBI suitability. During lumpectomy, a breast surgeon placed a bioabsorbable 3D fixed array tissue marker (BioZorb™, Hologic, Marlborough, MS) for enhanced visualization of the cavity boundaries. We defined the clinical target volume (CTV) as the delineable cavity plus a 1 cm isotropic expansion. We placed a 3mm isotropic planning target volume (PTV) expansion around the CTV. We treated each woman with 3000cGy delivered in 5 consecutive, daily, free-breathed fractions in either prone or supine positioning depending on individual anatomy. Patient treatment position was free-breathing in the prone position for 17 patients and supine in 3 patients using triggered imaging and fiducial tracking. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans used 10MV flattening filter free (FFF) beams delivered on a Varian Edge linear accelerator. We documented the following: adverse events (CTCAE 4.0), causality of the event to SBRT, and nurse- and patient- scored cosmesis (i.e., 1=excellent, 2=good, 3=fair, 4=poor) at pre-treatment baseline, 1 month post-treatment, and at each proceeding 6 month interval. We also clinically surveilled for disease recurrence. Results: We completed accrual and treatment of twenty patients. At time of submission, fourteen patients had completed 6-month follow-up, and eight patients had completed 12-month follow-up. No patients experienced grade ≥3 toxicity. Adverse events reported were mostly grade 1. Eighty-five percent of patient-scored cosmesis were excellent or good at baseline, with no evidence of deterioration at 1-month post-treatment (Baseline = 1.9, 1 month = 1.9; p = 0.914). Eighty-five percent of nurse-scored cosmesis reports were excellent or good at baseline, with no evidence of deterioration between baseline and 1-month post-treatment (Baseline = 1.95, 1 month = 1.90; p = 0.564). Eighty-six percent of patients had excellent or good patient- and nurse-scored cosmesis at 6 months, with either mean score of 1.71. Eighty-eight percent of patients had excellent or good patient- and nurse-scored cosmesis at 12 months, with mean cosmesis score of 1.50 and 1.63, respectively. Local control follow-up is immature, but no patients developed IBTR. Conclusions: Our study demonstrated that consecutive daily 5-fraction breast SBRT for APBI is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering partial breast irradiation in suitable women. As follow-up duration matures, we will report long term cosmetic outcome and recurrence. Citation Format: Yilan Liu, Christopher Veale, Diana Hablitz, Helen Krontiras, Michael Christian Dobelbower, Rachael Lancaster, Markus Bredel, Catherine Parker, Kimberly Keene, Evan Thomas, Drexell Hunter Boggs. Feasibility and short term toxicity of a consecutively delivered 5-fraction stereotactic body radiotherapy in early stage breast cancer patients receiving accelerated partial breast irradiation [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-18.