Baseline Karnofsky performance status is independently predictive of death within 30 days of intracranial radiation therapy completion for metastatic disease.

INTRODUCTION: For patients with brain metastases, palliative radiation therapy (RT) has long been a standard of care for improving quality of life and optimizing intracranial disease control. The duration of time between completion of palliative RT and patient death has rarely been evaluated. METHODS: A compilation of two prospective institutional databases encompassing April 2015 through December 2018 was used to identify patients who received palliative intracranial radiation therapy. A multivariate logistic regression model characterized patients adjusting for age, sex, admission status (inpatient versus outpatient), Karnofsky Performance Status (KPS), and radiation therapy indication. RESULTS: 136 consecutive patients received intracranial palliative radiation therapy. Patients with baseline KPS <70 (OR = 2.2; 95%CI = 1.6-3.1; p < 0.0001) were significantly more likely to die within 30 days of treatment. Intracranial palliative radiation therapy was most commonly delivered to provide local control (66% of patients) or alleviate neurologic symptoms (32% of patients), and was most commonly delivered via whole brain radiation therapy in 10 fractions to 30 Gy (38% of patients). Of the 42 patients who died within 30 days of RT, 31 (74%) received at least 10 fractions. CONCLUSIONS: Our findings indicate that baseline KPS <70 is independently predictive of death within 30 days of palliative intracranial RT, and that a large majority of patients who died within 30 days received at least 10 fractions. These results indicate that for poor performance status patients requiring palliative intracranial radiation, hypofractionated RT courses should be strongly considered.

Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol.

INTRODUCTION: Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates. METHODS: This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0-2 cm lesions, 14 Gy for 2.1-3 cm lesions, and 12 Gy for 3.1-4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90-05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria. DISCUSSION: This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).

Impact of the American Tax Payer Relief Act on stereotactic radiosurgery utilization in the United States.

INTRODUCTION: Single-fraction stereotactic radiosurgery (SRS) is delivered predominantly via two modalities: Gamma Knife, and linear accelerator (LINAC). Implementation of the American Tax Payer Relief Act (ATRA) in 2013 represented the first time limitations specifically targeting SRS reimbursement were introduced into federal law. The subsequent impact of the ATRA on SRS utilization in the United States (US) has yet to be examined. METHODS: The National Cancer Database from 2010-2016 identified brain metastases patients from non-small cell lung cancer throughout the US having undergone SRS. Utilization between GKRS and LINAC was assessed before (2010-2012), during (2013-2014) and after (2015-2016) ATRA implementation. RESULTS: In 2013, there was a substantial decrease of LINAC SRS in favor of GKRS in non-academic centers. Over the 3-year span immediately preceding ATRA implementation, 39% of all eligible SRS cases received LINAC. There was a modest decrease in LINAC utilization over the 2 years immediately following ATRA implementation (35%), followed by an increase over the next two years (40%). SRS modality showed differences over the three time periods (unadjusted, p = 0.043), primarily in non-academic centers (unadjusted, p = 0.003). CONCLUSIONS: ATRA implementation in 2013 caused an initial spike in Gamma Knife SRS utilization, followed by a decline to rates similar to the years before implementation. These findings indicate that the ATRA provision mandating Medicare reduction of outpatient payment rates for Gamma Knife to be equivalent with those of LINAC SRS had a significant short-term impact on the radiosurgical treatment of metastatic brain disease throughout the US, serving as a reminder of the importance/impact of public policy on treatment modality utilization by physicians and hospitals.

Analysis of Retrospective Versus Prospective Peer Review in a Multisite Academic Radiation Department.

Purpose: Our multisite academic radiation department reviewed our experience with transitioning from weekly primarily retrospective to daily primarily prospective peer review to improve plan quality and decrease the rate of plan revisions after treatment start. Methods and Materials: This study was an institutional review board-approved prospective comparison of radiation treatment plan review outcomes of plans reviewed weekly (majority within 1 week after treatment start) versus plans reviewed daily (majority before treatment start, except brachytherapy, frame-based radiosurgery, and some emergent plans). Deviations were based on peer comments and considered major if plan revisions were recommended before the next fraction and minor if modifications were suggested but not required. Categorical variables were compared using χ2 distribution tests of independence; means were compared using independent t tests. Results: In all, 798 patients with 1124 plans were reviewed: 611 plans weekly and 513 plans daily. Overall, 76 deviations (6.8%) were noted. Rates of any deviation were increased in the daily era (8.6% vs 5.2%; P = .026), with higher rates of major deviations in the daily era (4.1% vs 1.6%; P = .012). Median working days between initial simulation and treatment was the same across eras (8 days). Deviations led to a plan revision at a higher rate in the daily era (84.1% vs 31.3%; P < .001). Conclusions: Daily prospective peer review is feasible in a multisite academic setting. Daily peer review with emphasis on prospective plan evaluation increased constructive plan feedback, plan revisions, and plan revisions being implemented before treatment start.

Literature review of management of brain metastases from germ cell tumors.

OBJECTIVE: In this review article, we discuss the role of chemotherapy, surgery, and radiation therapy in the treatment of brain metastases from germ cell tumors (GCT). BACKGROUND: GCT rarely metastasize to the brain and there is limited data to guide management. Most instances of brain metastases occur in patients with non-seminomatous germ cell tumors (NSGCT). METHODS: We searched PubMed using the terms 'central nervous system (CNS) metastases' or 'brain metastases' and 'germ cell' from 2011 through August 2021. Review articles and prospective trials related to the treatment of brain metastases in GCT were included in addition to articles obtained by hand search of the references and clinical practice guidelines. CONCLUSIONS: We highlight the importance of using chemotherapy as first-line therapy in most situations. We discuss the very minimal data regarding surgery and its primary role when there is significant mass effect or brain shift. We also compare whole brain radiation therapy (WBRT) with the use of radiosurgery. We then provide overall recommendations based on the reviewed data and our experience as a referral center for GCT.

Discovery of increased number or interval growth of brain metastases on same-day GammaKnife™ planning MRI: Predicting factors and patient outcomes.

Purpose: To determine factors associated with increased risk of finding new and/or enlarged brain metastases (BM) on GammaKnife™ (GK) MRI and their impact on patient outcomes. Results: 43.9% of patients showed BM growth, 32.9% had additional brain metastases (aBM), and 18.1 % had both. Initial brain metastasis velocity (iBMV) was associated with finding aBM. Time between diagnostic MRI (dMRI) and GK MRI was associated with interval growth and each day increased this risk by 2%. Prior brain metastasectomy and greater time between either dMRI or latest extracranial RT and GK MRI predicted both aBM and BM growth. aBM and/or BM growth led to management change in 1.8% of cases and were not associated with OS or incidence of distant intracranial failure. Conclusions: Number of metastases seen on dMRI and iBMV predicted both aBM and/or BM growth, however, these factors did not significantly affect survival or incidence of distant intracranial failure.

Safety and efficacy of GammaTile intracranial brachytherapy implanted during awake craniotomy.

INTRODUCTION: GammaTile intracranial brachytherapy (cesium-131 seeds) has demonstrated encouraging safety and local control results, and recently received Food and Drug Administration clearance for newly diagnosed and recurrent brain tumors. The authors present the first reported case of GammaTile intraoperative brachytherapy performed during an awake craniotomy. METHODS: A 50-year-old man had a biopsy-proven, 2.8 cm left lateral frontal glioblastoma lesion nearing Broca's area on MRI. Despite several interventions (craniotomy, adjuvant chemoradiation, tumor treating fields) tumor progression occurred near the left parietal resection cavity. Re-resection was planned with awake craniotomy and language mapping. A preoperative planning session involving Radiation Oncology and Neurosurgery identified the area of the expected postoperative bed, and consequently five GammaTiles were ordered, each containing 4 cesium-131 3.5 U seeds. RESULTS: During surgery, tumor mapping and bipolar stimulation were performed while the patient spoke in complete sentences. Speech arrest occurred upon stimulation at the posterior edge of the gyrus, indicative of language cortex. Microsurgical maximal safe resection subsequently occurred, and areas at risk for residual/recurrence disease were determined in consultation with Radiation Oncology. Subsequently, Neurosurgery placed all five GammaTiles (20 cesium-131 seeds total) after which closure was completed and radioactive surveys of the room remained within state statue. Postoperative dosimetry yielded excellent coverage. CONCLUSIONS: The first reported case of GammaTile intraoperative brachytherapy during awake craniotomy supports the safety and feasibility of this treatment strategy. This case indicates that for patients with tumors adjacent to eloquent cortex, awake craniotomy can allow for custom implantation of intraoperative brachytherapy following maximum safe resection.

Analysis of Virtual Versus In-Person Prospective Peer Review Workflow in a Multisite Academic Radiation Oncology Department.

PURPOSE: In radiation oncology, peer review is a process where subjective treatment planning decisions are assessed by those independent of the prescribing physician. Before March 2020, all peer review sessions occurred in person; however due to the COVID-19 pandemic, the peer-review workflow was transitioned from in-person to virtual. We sought to assess any differences between virtual versus in-person prospective peer review. METHODS AND MATERIALS: Patients scheduled to receive nonemergent nonprocedural radiation therapy (RT) were presented daily at prospective peer-review before the start of RT administration. Planning software was used, with critical evaluation of several variables including treatment intent, contour definition, treatment target coverage, and risk to critical structures. A deviation was defined as any suggested plan revision. RESULTS: In the study, 274 treatment plans evaluated in-person in 2017 to 2018 were compared with 195 plans evaluated virtually in 2021. There were significant differences in palliative intent (36% vs 22%; P = .002), but not in total time between simulation and the start of treatment (9.2 vs 10.0 days; P = .10). Overall deviations (8.0% in-person vs 2.6% virtual; P = .015) were significantly reduced in virtual peer review. CONCLUSIONS: Prospective daily peer review of radiation oncology treatment plans can be performed virtually with similar timeliness of patient care compared with in-person peer review. A decrease in deviation rate in the virtual peer review setting will need to be further investigated to determine whether virtual workflow can be considered a standard of care.

Predictors of linear accelerator versus Gamma Knife stereotactic radiosurgery use for brain metastases in the United States.

INTRODUCTION: Stereotactic radiosurgery (SRS) for brain metastases is predominantly delivered via single-fraction Gamma Knife SRS (GKRS) or linear accelerator (LINAC) in up to five fractions. Predictors of SRS modality have been sparsely examined on a nationwide level. METHODS: An observational cohort study was performed on patients receiving SRS for brain metastases from non-small cell lung cancer from 2010 to 2016 at Commission on Cancer-accredited hospitals throughout the United States (US). A multivariable logistic regression model characterized SRS receipt, adjusting for patient age, dose, geographic location of treatment, facility type, and distance from treatment facility. RESULTS: A total of 2,684 patients received GKRS, while 1,643 patients received LINAC SRS. After adjusting for significant covariates, treatment at non-academic facilities was associated with increased LINAC SRS receipt, most prominently in the Midwestern (OR=6.23;p<0.001), Northeastern (OR=4.42;p<0.001), and Southern US (OR=1.96;p<0.001). Compared to patients receiving 12-17 Gy, patients receiving doses of 18-19 Gy (OR=1.42;p=0.025), 20-21 Gy (OR=1.82;p<0.001), and 22-24 Gy (OR=3.11;p<0.001) were more likely to receive LINAC SRS; similarly, patients located within 20 miles of a radiation treatment facility were more likely to receive LINAC SRS (OR=1.27;p=0.007). CONCLUSIONS: Despite Gamma Knife being more prominently used over LINAC for SRS, patients treated at a non-academic facility outside of the Western US or requiring increased radiation dose were substantially more likely to receive LINAC over Gamma Knife. Additionally, patients residing in close proximity to a treatment center were 27% more likely to receive LINAC, likely indicative of the increased geographic accessibility of LINAC compared with GKRS.

Cost Analysis of Audiovisual-Assisted Therapeutic Ambiance in Radiation Therapy (AVATAR)-Aided Omission of Anesthesia in Radiation for Pediatric Malignancies.

PURPOSE: Because children cannot reliably remain immobile during radiation therapy (RT) for cancer anatomy targeting requiring millimeter precision, daily anesthesia plays a large role in each RT session. Unfortunately, anesthesia is a source of financial burden for patients' families and is invasive and traumatic. This study attempts to assess the cost-savings benefit of audiovisual-assisted therapeutic ambiance in radiation therapy (AVATAR)-aided omission of pediatric anesthesia in RT. METHODS AND MATERIALS: The baseline time of anesthesia during RT was derived from documented anesthesia billing time during RT simulation at our institution and from the published literature. Current Procedural Terminology and relative value unit codes encompassing anesthesia-related charges from radiation oncology and anesthesia were analyzed in concert with this value to calculate the total cost of pediatric anesthesia per RT session. RESULTS: The mean number of RT fractions administered per patient with AVATAR-directed anesthesia omission at our institution was 19.0, similar to the 17.6 previously reported. At a mean anesthesia time exceeding 30 minutes (with mean RT duration of 4 weeks), the cost of pediatric anesthesia per RT fraction in non-AVATAR sessions was $1,904.35, yielding a total RT treatment anesthesia cost of $38,087.00 per patient (including simulation). Patients at our institution were not billed for AVATAR-assisted RT. CONCLUSIONS: The ability of AVATAR to obviate the need for daily anesthesia in pediatric RT provides substantial cost-savings. These findings argue for increased utilization of AVATAR and for analyses of RT targeting the accuracy of AVATAR versus conventional anesthesia-guided treatment of pediatric malignancies.

Effects of Proton Center Closure on Pediatric Case Volume and Resident Education at an Academic Cancer Center.

PURPOSE: To analyze effects of closure of an academic proton treatment center (PTC) on pediatric case volume, distribution, and resident education. METHODS AND MATERIALS: This was a review of 412 consecutive pediatric (age ≤18 years) cases treated at a single institution from 2012 to 2016. Residents' Accreditation Council for Graduate Medical Education case logs for the same years were also analyzed. Characteristics of the patient population and resident case volumes before and after closure of the PTC are reported. RESULTS: Overall pediatric new starts declined by approximately 50%, from 35 to 70 per 6 months in 2012 to 2014 to 22 to 30 per 6 months in 2015 to 2016. Central nervous system (CNS) case volume declined sharply, from 121 patients treated in 2012 to 2015 to 18 patients in 2015 to 2016. In 2012 to 2014 our institution treated 36, 24, and 17 patients for medulloblastoma/intracranial primitive neuroectodermal tumor, ependymoma, and low-grade glioma, respectively, compared with 0, 1, and 1 patient(s) in 2015 to 2016. Forty-nine patients were treated with craniospinal radiation (CSI) from 2012 to 2014, whereas only 2 patients underwent CSI between 2015 and 2016. Hematologic malignancy patient volume and use of total body irradiation remained relatively stable. Patients treated when the PTC was open were significantly younger (9.1 vs 10.7 years, P=.010) and their radiation courses were longer (35.4 vs 20.9 days, P<.0001) than those treated after its closure. Resident case logs showed only a small decline in total pediatric cases, because the percentage of pediatric cases covered by residents increased after PTC closure; however, residents logged fewer CNS cases after PTC closure versus before. CONCLUSIONS: Overall pediatric case volume decreased after PTC closure, as did the number of patients treated for potentially curable CNS tumors. Our findings raise important questions regarding resident training in pediatric radiation oncology as these cases become increasingly concentrated at specialized centers.

Radiation-Induced Cerebral Microbleeds in Pediatric Patients With Brain Tumors Treated With Proton Radiation Therapy.

PURPOSE: Proton beam radiation therapy (PBT) has been increasingly used to treat pediatric brain tumors; however, limited information exists regarding radiation-induced cerebral microbleeds (CMBs) among these patients. The purpose of this study was to evaluate the incidence, risk factors, and imaging appearance of CMBs in pediatric patients with brain tumors treated with PBT. MATERIALS AND METHODS: A retrospective study was performed of 100 pediatric patients with primary brain tumors treated with PBT. CMBs were diagnosed by examination of serial magnetic resonance imaging scans, including susceptibility-weighted imaging. Radiation therapy plans were analyzed to determine doses to individual CMBs. Clinical records were used to determine risk factors associated with the development of CMBs in these patients. RESULTS: The mean age at time of PBT was 8.1 years. The median follow-up duration was 57 months. The median time to development of CMBs was 8 months (mean, 11 months; range, 3-28 months). The percentage of patients with CMBs was 43%, 66%, 80%, 81%, 83%, and 81% at 1 year, 2 years, 3 years, 4 years, 5 years, and >5 years from completion of proton radiation therapy. Most of the CMBs (87%) were found in areas of brain exposed to ≥30 Gy. Risk factors included maximum radiation therapy dose (P = .001), percentage and volume of brain exposed to ≥30 Gy (P = .0004, P = .0005), and patient age at time of PBT (P = .0004). Chemotherapy was not a significant risk factor (P = .35). No CMBs required surgical intervention. CONCLUSIONS: CMBs develop in a high percentage of pediatric patients with brain tumors treated with proton radiation therapy within the first few years after treatment. Significant risk factors for development of CMBs include younger age at time of PBT, higher maximum radiation therapy dose, and higher percentage and volume of brain exposed to ≥30 Gy. These findings demonstrate similarities with CMBs that develop in pediatric patients with brain tumor treated with photon radiation therapy.

Brainstem metastases treated with Gamma Knife stereotactic radiosurgery: the Indiana University Health experience.

Brainstem metastases offer a unique challenge in cancer treatment, yet stereotactic radiosurgery (SRS) has proven to be an effective modality in treating these tumors. This report discusses the clinical outcomes of patients with brainstem metastases treated at Indiana University with Gamma Knife (GK) radiosurgery from 2008 to 2016. 19 brainstem metastases from 14 patients who had follow-up brain imaging were identified. Median tumor volume was 0.04 cc (range: 0.01-2.0 cc). Median prescribed dose was 17.5 Gy to the 50% isodose line (range: 14-22 Gy). Median survival after GK SRS treatment to brainstem lesion was 17.2 months (range: 2.8-45.6 months). The experience at Indiana University confirms the safety and efficacy of range of GK SRS prescription doses (14-22 Gy) to brainstem metastases.

Toxicity of Radiosurgery for Brainstem Metastases.

BACKGROUND: Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed. METHODS: Twenty-nine retrospective studies investigating SRS for BSM were reviewed. RESULTS: The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811). CONCLUSIONS: Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04-2.8 cc does not predict for toxicity.

Survival and complications of stereotactic radiosurgery: A systematic review of stereotactic radiosurgery for newly diagnosed and recurrent high-grade gliomas.

BACKGROUND: Utilization of stereotactic radiosurgery (SRS) for treatment of high-grade gliomas (HGGs) has been slowly increasing with variable reported success rates. OBJECTIVE: Systematic review of the available data to evaluate the efficacy of SRS as a treatment for HGG with regards to median overall survival (OS) and progression-free survival (PFS), in addition to ascertaining the rate of radiation necrosis and other SRS-related major neurological complications. METHODS: Literature searches were performed for publications from 1992 to 2016. The pooled estimates of median PFS and median OS were calculated as a weighted estimate of population medians. Meta-analyses of published rates of radiation necrosis and other major neurological complications were also performed. RESULTS: Twenty-nine studies reported the use of SRS for recurrent HGG, and 16 studies reported the use of SRS for newly diagnosed HGG. For recurrent HGG, the pooled estimates of median PFS and median OS were 5.42 months (3-16 months) and 20.19 months (9-65 months), respectively; the pooled radiation necrosis rate was 5.9% (0-44%); and the pooled estimates of major neurological complications rate was 3.3% (0-23%). For newly diagnosed HGG, the pooled estimates of median PFS and median OS were 7.89 months (5.5-11 months) and 16.87 months (9.5-33 months) respectively; the pooled radiation necrosis rate was 6.5% (0-33%); and the pooled estimates of other major neurological complications rate was 1.5% (0-25%). CONCLUSION: Our results suggest that SRS holds promise as a relatively safe treatment option for HGG. In terms of efficacy at this time, there are inadequate data to support routine utilization of SRS as the standard of care for newly diagnosed or recurrent HGG. Further studies should be pursued to define more clearly the therapeutic role of SRS.

Radiation-Induced Large Vessel Cerebral Vasculopathy in Pediatric Patients With Brain Tumors Treated With Proton Radiation Therapy.

PURPOSE: The purpose of this research was to evaluate the incidence, time to development, imaging patterns, risk factors, and clinical significance of large vessel cerebral vasculopathy in pediatric patients with brain tumors treated with proton radiation therapy. METHODS AND MATERIALS: A retrospective study was performed on 75 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation-induced large vessel cerebral vasculopathy (RLVCV) was defined as intracranial large vessel arterial stenosis or occlusion confirmed on magnetic resonance angiography, computed tomographic angiography, catheter angiography, or a combination of these within an anatomic region with previous exposure to proton beam therapy and not present before radiation therapy. Clinical records were used to determine the incidence, timing, radiation dose to the large vessels, and clinical significance associated with the development of large vessel vasculopathy in these patients. RESULTS: RLVCV was present in 5 of 75 (6.7%) patients and included tumor pathologic features of craniopharyngioma (n=2), ATRT (n=1), medulloblastoma (n=1), and anaplastic astrocytoma (n=1). The median time from completion of radiation therapy to development was 1.5 years (mean, 3.0 years; range, 1.0-7.5 years). Neither mean age at the time of radiation therapy (5.1 years) nor mean radiation therapy dose to the large vessels (54.5 Gy) was a statistically significant risk factor. Four of the 5 patients with RLVCV presented with acute stroke and demonstrated magnetic resonance imaging evidence of acute infarcts in the expected vascular distributions. Angiography studies demonstrated collateral vessel formation in only 2 of the patients with RLVCV. No patients demonstrated acute hemorrhage or aneurysm. Two patients were treated with pial synangiomatosis surgery. CONCLUSIONS: RLVCV can occur in pediatric patients with brain tumors treated with proton radiation therapy. Further studies are necessary to determine potential risk factors for large vessel vasculopathy with proton radiation therapy in comparison with conventional photon radiation therapy.

Dynamic collimator optimization compared with fixed collimator angle in arc-based stereotactic radiotherapy: a dosimetric analysis.

OBJECT: The purpose of this study was to determine the effect of static and dynamic collimator optimization when using a micromultileaf collimator (mMLC) in dynamic-arc stereotactic radiosurgery (SRS) by evaluating the dose to healthy peritumoral tissue. METHODS: Thirty patients previously treated for intracranial lesions with the BrainLAB mMLC underwent retrospective replanning. Three collimator optimization strategies were compared for a simulated SRS treatment plan, as follows: Strategy 1, static collimation fixed at 90 degrees throughout arcs; Strategy 2, static collimator settings optimized for each arc; and Strategy 3, dynamic collimator settings optimized every 10 degrees throughout treatment arcs. Dose-volume histograms for a 0.7-cm shell of healthy peritumoral tissue were quantitatively compared. Collimator optimization schemes (Strategies 2 and 3) significantly decreased the volume of peritumoral tissue that is irradiated when compared with static collimation at 90 degrees (Strategy 1). The volume was reduced by 40.6% for Strategy 2 (95% confidence interval [CI] +/- 11) and by 47.1% for Strategy 3 (95% CI +/- 8.1) at the 95% isodose; by 28.4% for Strategy 2 (95% CI +/- 4.9) and 39.1% for Strategy 3 (95% CI +/- 6) at the 90% isodose; and by 18.2% for Strategy 2 (95% CI +/- 8.1) and 25.4% for Strategy 3 (95% CI +/- 7.1) at the 80% isodose. Serial collimator optimization throughout the treatment arcs (Strategy 3) reduced the mean volume of peritumoral tissue irradiated when compared with static collimator optimization (Strategy 2), by 16.1% (95% CI +/- 1.5) at 95% isodose, by 11.7% (95% CI +/- 1) at 90% isodose, and by 8.2% (95% CI +/- 1.2) at 80% isodose regions. In specific cases, linear or polynomial functions were formulated to optimize collimator settings dynamically throughout treatment arcs. CONCLUSIONS: Dynamic collimator optimization during arc-based SRS decreases the volume of healthy peritumoral tissue treated with high doses of radiation and appears to be an effective method of improving target conformality. This study is the first step toward determination of a smoothing function algorithm to allow for true dynamic collimation during SRS.