Linac-based Stereotactic Radiosurgery Research Articles

Frameless LINAC Stereotactic Radiosurgery for Brain Metastasis using VMAT: A Review of 20 Cases and Institutional Experience

Background/Objectives: Brain metastases can be treated with Stereotactic Radiosurgery (SRS), a precise radiation therapy approach. This study aimed to review the feasibility and efficacy of frameless LINAC-based SRS using Volumetric Modulated Arc Therapy (VMAT) in a group of 20 patients. Methods: Twenty patients diagnosed with brain metastases received VMAT SRS. Clinical characteristics such as demographics, gender, performance status, number of brain metastases, neurological symptoms, neurosurgical procedures, systemic status, prior treatments, lesion size, SRS dose, local control after SRS and toxicity profile were assessed. Results: The median age of patients was 49.5 years (range 32-63), with 80% being female. Most patients (85%) had ECOG scores of 0-1. The median lesion size treated was 16 mm, with a median dose of 20 Gy for the first SRS (SRS1). After SRS1, 75% of patients achieved Local Control (LC), with a median duration of LC of 7.65 months. Six patients received a second SRS (SRS2) with a median dose of 20 Gy to a different location. Two out of six patients achieved LC after SRS2. Radiation necrosis occurred in 2 cases (10%). The median follow-up time from brain metastasis to the last follow-up was 20.31 months (range 0-50.43 months). Conclusion: Frameless LINAC-based VMAT SRS appears to be a promising treatment option for brain metastases. Initial findings suggest favorable local control rates and further research is needed to optimize treatment strategies.

Frameless LINAC Stereotactic Radiosurgery for Brain Metastasis using VMAT: A Review of 20 Cases and Institutional Experience

Background/Objectives: Brain metastases can be treated with Stereotactic Radiosurgery (SRS), a precise radiation therapy approach. This study aimed to review the feasibility and efficacy of frameless LINAC-based SRS using Volumetric Modulated Arc Therapy (VMAT) in a group of 20 patients. Methods: Twenty patients diagnosed with brain metastases received VMAT SRS. Clinical characteristics such as demographics, gender, performance status, number of brain metastases, neurological symptoms, neurosurgical procedures, systemic status, prior treatments, lesion size, SRS dose, local control after SRS and toxicity profile were assessed. Results: The median age of patients was 49.5 years (range 32-63), with 80% being female. Most patients (85%) had ECOG scores of 0-1. The median lesion size treated was 16 mm, with a median dose of 20 Gy for the first SRS (SRS1). After SRS1, 75% of patients achieved Local Control (LC), with a median duration of LC of 7.65 months. Six patients received a second SRS (SRS2) with a median dose of 20 Gy to a different location. Two out of six patients achieved LC after SRS2. Radiation necrosis occurred in 2 cases (10%). The median follow-up time from brain metastasis to the last follow-up was 20.31 months (range 0-50.43 months). Conclusion: Frameless LINAC-based VMAT SRS appears to be a promising treatment option for brain metastases. Initial findings suggest favorable local control rates and further research is needed to optimize treatment strategies.

Frameless, Virtual Cone Linac-based Stereotactic Radiosurgery for Essential & Parkinsonian Tremor: A Phase I/II Prospective Clinical Trial (S35.001)

Frameless, Virtual Cone Linac-based Stereotactic Radiosurgery for Essential & Parkinsonian Tremor: A Phase I/II Prospective Clinical Trial (S35.001)

Clinical Results and Hematologic Predictors of Linear Accelerator–Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis in Patients Aged 75 Years or Older: A Retrospective Study

This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (linac)-based, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Between January 2011 and November 2021, 101 consecutive elderly patients with BM were treated by linac-based SRS or fSRT using linac with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years. The tumors originated from the lungs (n = 90, 89.1%), colon (n = 2, 2.0%), and others (n = 9, 8.8%) in these EPs. The median pretreatment Karnofsky Performance Scale (KPS) score was 80 (range: 40–100). The median follow-up time was 10 (range: 0–76) months, as was the median survival time. The 6-month and 1 and 2-year survival rates in the EP group were 58.3%, 43.2%, 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years were 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs were 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio (NLR) >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (p<0.001). In the EPs, the prognostic factors associated with prolonged survival time in the Cox proportional hazards model were being female and a good pretreatment KPS score. The findings of our study highlight the efficacy of linac-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. NLR can be an important factor in treatment decisions for EPs with BMs.

Effect of prescription isodose line on tissue sparing in linear accelerator-based stereotactic radiosurgery treating multiple brain metastases using dynamic conformal arcs.

Linear accelerator-based stereotactic radiosurgery (SRS) has become a mainstay for simultaneous management of multiple intracranial targets. Recent improvements in treatment planning systems (TPS) have enabled treatment of multiple brain metastases using dynamic conformal arcs (DCA) and a single treatment isocenter. However, as the volume of healthy tissue receiving at least 12Gy (V12) is linked to the probability of developing radionecrosis, balancing target coverage while minimizing V12 is a critical factor affecting SRS plan quality. Current TPS allow users to adjust various parameters influencing plan optimization. The purpose of this work is to quantify the effect of negative margins on V12 for cranial SRS plans managing multiple brain metastases. Using the Brainlab Elements v3.0 TPS (Brainlab, Munich, Germany), we calculated V10, V12, V15, monitor units, and conformity index for seventeen SRS plans treating 2-10 metastases on our Elekta Versa HD (Elekta, Stockholm, Sweden) linear accelerator. We compared plans optimized using 70%-90% prescription isodose lines (IDL) in 5% increments. Irrespective of the number of treated metastases, optimization at a lower prescription IDL reduced V10, V12, and V15 and increased MU compared to the 90% IDL (p<0.01). However, comparing the 70% and 75% IDL optimizations, there was little difference in tissue sparing. The conformity index showed no consistent trends at different IDLs due to a significant spread in case data. For our plans treating up to 10 metastases, diminishing returns for tissue sparing at IDLs below 80% paired with increasing treatment MU and dosimetric hot spot made optimization at lower IDLs less favorable. In our clinic, after consulting with a physician, it was determined that optimization at the 80% IDL achieved the best balance of V12, treatment MU, and maximum dose. Clinics implementing LINAC-based SRS programs may consider using similar evaluations to develop their own clinical protocols.

A dosimetric study comparing Cyberknife and LINAC-based stereotactic radiotherapy or radiosurgery treatments

BackgroundWhile Gamma Knife and CyberKnife are commonly used for Stereotactic radiosurgery (SRS), their availability is limited. In contrast, linac-based SRS using linear accelerators (linacs) is more accessible and widely used. PurposeOur study aims to evaluate Linac-based SRS with the Varian RapidArc technique for treating brain metastases. The primary objective is to compare the quality of treatment plans between RapidArc and CyberKnife modalities. Materials & methodsTen patients with a single brain metastasis were treated using the CyberKnife machine with prescribed doses ranging from 18 to 25 Gy. Treatment plans utilized Multiplan software for CyberKnife and Eclipse for RapidArc plans. The plans were evaluated based on dose metrics for the target and critical structures, treatment time, and brain tissue volume. ResultsBoth techniques provided acceptable Gross tumor volume coverage and organs at risk sparing. CyberKnife delivered a higher integral dose to the Gross tumor volume and brain tissues compared to RapidArc (p < 0.05). The conformity index was slightly better in RapidArc (1.14 ± 0.25) compared to CyberKnife (1.22 ± 0.12), but the difference was not statistically significant (p > 0.05). However, CyberKnife exhibited a better dose gradient index (4.52 ± 0.99) compared to RapidArc (8.6 ± 7.28). The treatment time in RapidArc was significantly lower compared to CyberKnife, p < 0.05. RapidArc demonstrated lower minimum and maximum doses to some organs at risk, although some differences were not statistically significant. For normal brain tissues, V12Gy was significantly lower with RapidArc (3.27 ± 2.92) compared to CyberKnife (4.09 cc ± 3.27). ConclusionThe RapidArc technique is capable of achieving similar treatment quality as CyberKnife systems for SRS treatments. It offers improved target coverage, higher conformity, and homogeneous dose distribution within the Planning target volume if homogeneity is desirable in some intuitions or cases. In addition, it can also achieve low integral doses to organs at risk and brain tissues.

Editorial: LINAC-based stereotactic radiosurgery in daily practice

Editorial: LINAC-based stereotactic radiosurgery in daily practice

RADT-20. STEREOTACTIC RADIOSURGERY FOR 15 OR MORE BRAIN METASTASES

Abstract BACKGROUND Patients with ≥ 15 brain metastases(BM) continue to be treated with whole brain radiation therapy(WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery(SRS), with the aim of evaluating safety, cognitive outcomes, and survival. METHODS Patients who received SRS for ≥ 15 BMs in 1-5 fractions from 2014-2022 using the previously described single isocenter multi-target technique were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System(PROMIS) scores. RESULTS A total of 124 patients treated with LINAC-based SRS were included. The mean and median number of lesions treated per patient was 24.8 and 20, respectively (range 15 – 94). Most common primary histologies were lung(47.6%), melanoma(21.0%), and breast(14.5%). The median SRS dose was 24 Gy(range 18 – 30 Gy). The rate of any grade radiation necrosis (RN) and ≥ grade 3 RN were 15.3% and 3.2% respectively. New onset seizures were seen in 2.4% and alopecia in 2.4%. Median follow-up was 5.1 months(m). When cognitive data were available, 25 of 31 patients had a stable or improved PROMIS score. The 12m local control was 97.6% while overall intracranial control was 20.8%. One-year freedom from neurological death, leptomeningeal disease, and salvage WBRT were 85.6%, 87.6% and 71.7% respectively. Median overall survival(OS) from brain metastases diagnosis was 11.3m(95% CI 7.2m – 15.3m). On univariate analysis, no prior WBRT(p = 0.038), higher KPS(p = 0.002) and systemic therapy after SRS(p &amp;lt; 0.001) predicted for improved OS. CONCLUSIONS We present here the largest study evaluating SRS for patients with ≥ 15 BMs. We found that SRS was safe, had favorable cognitive outcomes, and comparable survival outcomes to contemporary studies evaluating WBRT in this patient population. Our study supports further randomized studies comparing SRS and memory avoidance WBRT approaches for patients with ≥ 15 BMs.

RADT-22. STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMA WITH RADIOGRAPHIC BRAINSTEM COMPRESSION

Abstract BACKGROUND The safety of single treatment stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) with radiographic evidence of brainstem compression- but without motor deficit- is controversial. Data on linac-based SRS in this setting are scarce. We address this deficit in the literature with a report of outcome of an unselected series of patients with VS with radiographic brainstem compression treated with linac SRS our institution. METHODS We included patients with unilateral VS of any size with radiographic brainstem compression at the time of SRS. All patients were without serious brainstem neurologic deficits at the time of SRS. The SRS prescription dose was 12.5 Gy in a single fraction using 6MV photon beams produced by a linear accelerator and delivered with a multiple arc technique. Inclusion in this study required at least 1 year of radiographic follow-up with magnetic resonance imaging (MRI). The primary endpoint was freedom from serious brainstem toxicity (CTCAEv5 grade &amp;gt;3); secondary endpoint was freedom from tumor enlargement considered to represent tumor progression, or any type of enlargement requiring surgical intervention. We also assessed serious cranial nerve complications, excluding hearing loss, defined as CTCAEv5 grade 3 toxicity. RESULTS Among 139 patients, the median MRI follow-up time was 5 years and the median tumor size was 2.5 cm greatest axial dimension and 5cc in volume. The median brainstem D0.03cc = 12.6 Gy, and the median brainstem V10Gy = 0.4cc. At 5 years, the actuarial freedom from serious brainstem toxicity was 100% (zero cases), and freedom from tumor enlargement, either requiring surgery or due to progression, was 90%. The rate of grade 3 facial nerve damage in patients without tumor enlargement was 0.9% (1/113). CONCLUSION Linac-based SRS as delivered in our series for VS with radiographic brainstem compression is safe and effective.

RADT-21. LINEAR ACCELERATOR BASED RADIOSURGERY WITH DYNAMIC CONFORMAL ARCS FOR PATIENTS WITH MULTIPLE BRAIN METASTASES: A PROSPECTIVE COHORT STUDY

Abstract PURPOSE Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is gaining popularity as an alternative due to its high delivery efficiency and improved accessibility. This study focuses on the radiosurgery protocol of a single institution, utilizing single-isocenter multi-target SRS treatment with an inverse-optimized dynamic conformal arc technique. Materials &amp; METHODS A prospective cohort study was conducted from August 2020. The study protocol was approved by the Research Ethics Committee. Patients with brain tumors referred for SRS were treated based on the indications. Prescription doses were determined by target size and radiation oncologists. The protocol included a 1-2 mm expansion of tumors for the planning target volume (PTV), with a requirement of at least 85% PTV coverage. At least three non-coplanar arcs are needed. Competing risk survival analysis was used to assess the cumulative incidence of failure. RESULTS A total of 57 patients with 190 brain tumors underwent SRS in this study. 12 patients (21.1%) received at least 2 radiation courses for recurrent lesions. Tumor sizes ranged from 0.45 to 8.0 cm (median 1.41 cm). The maximal dose relation ranged between 71.5% and 91.4% (median 81.6). The conformal index ranged from 1.08 to 2.19 (median 1.19), and the dose gradient index ranged from 2.19 to 6.95 (median 3.59). The 1-year cumulative incidence of local failure and intracranial distant failure rates were 10.8% and 35.6%, respectively. CONCLUSION LINAC-based SRS using dynamic conformal arcs achieves optimal tumor coverage and a high dose gradient with ease. It demonstrates a low rate of local failure, effectively protects normal brain tissue, and allows for the postponement of whole brain radiotherapy, enabling patients to maintain a normal quality of life. In conclusion, LINAC-based SRS with dynamic conformal arcs may be a beneficial treatment option for brain metastases, even with a high lesion count, particularly in institutions equipped with LINAC.

Conformality Indices and Brain Dose Objective for Multi-Lesion Brain Single Isocenter Linac-Based Stereotactic Radiosurgery

The lack of recommendation on Linac-based stereotactic radiosurgery (SRS) and radiotherapy (SRT) plan quality for multi-lesion brain metastasis results in planning heterogeneity. The use of MLCs in the delivery is expected to add extra leakage when multi-lesions are treated simultaneously, and no recommendations availability in literature. We aimed to identify conformality indices and plan objectives that would guide multi-brain metastasis SRS & SRT MATERIALS/METHODS: We performed a retrospective analysis of clinically accepted brain metastasis radiotherapy plans treated using SRS and SRT at our department. Each plan was assessed for four metrics: Two conformality indices, including R50% referring to the ratio of the 50% dose cloud to the PTV, and %D1cm referring to the percentage of dose at 1cm away from PTV in any direction. One dose objective, V12 Gy referring to the brain volume receiving 12 Gy, and one delivery efficiency parameter, the modulation factor, defined as the ratio of the total MU to the prescribed dose. Each parameter was evaluated as a function of total PTV volume and number of lesions. A total of 107 plans were analyzed. The analyzed plans included pre- and post-operative treated brain metastasis with 86% with ≤ 4 lesions (median is 2, IQR is 3), 80% of the plans received single fraction and 43% of plans have a total PTV volumes of ≤ 1cc (median is 2.2cc and IQR is 7.5cc). We used a two tail T-test to check for correlation. The 50% relative dose gradient, R50%, was found to be dependent on PTV volume (P < 0.001), and a power law was used to fit the data. The brain volume, V12 Gy, was also found to be dependent on total PTV volume (P < 0.0001) and a linear curve was used to fit V12 Gy vs PTV. We did not find correlation between the number of lesions and R50% and or V12 Gy (p-value = 0.154 and 0.736, respectively). The dose gradient at 1cm away in any direction from PTV, %D1cm, has a median, average and a S.D. of 32%, 33% and 9%, respectively. 85% of all plans have %D1cm<42% which falls within 1 S.D. In addition, we found %D1cm to be dependent on both PTV volume and number of lesions (P < 0.001 for both). The modulation factor (MF) has a median, average and a S.D. of 2.9, 3.0 and 1.5, respectively. We found that 81% of all plans has MF < 4.5, which is within the 1 S.D. It has a positive correlation of 0.628 with the number of lesions. We found a clear correlation between the total PTV volumes and R50% and V12 Gy, and a fit line was used to relate each parameter to the total PTV volume. As for %D1cm and MF, we found that the average value within 1 S.D. is adequate to include > 80% of the plan. We propose these four parameters to fill the gap for plan quality for Linac-based SRS and SRT. Further evaluation and validation of our results on larger cohort is needed to allow generalizability and applicability of the results and correlation with clinical outcomes to guide clinical decision making.

Stereotactic Radiosurgery (SRS) for Large Brain Metastases: Dosimetric and Clinical Predictors of Local Progression and Radionecrosis

Stereotactic radiosurgery (SRS) provides high rates of local control for small brain metastases with low rates of radionecrosis (RN). Larger targets are associated with increased risk of both local progression (LP) and RN. In this analysis, we hypothesized that dosimetric and clinical parameters predict for risk of LP and RN in SRS targets larger than two centimeters. We retrospectively reviewed patients with one or more targets with either an intact versus post-operative cavity larger than 2.0 cm treated with LINAC-based SRS between 2017 and 2022 at one institution. We assessed for association between patient, treatment, and disease variables with LP and RN. Variables assessed included tumor resection status, PDL1 positivity, target volume, maximum and minimum target dose, EQD2 and BED (a/b = 2 for necrosis and a/b = 10 for tumor control), as well as receipt of steroids, bevacizumab, or systemic therapy before or after SRS. Radionecrosis was determined by characteristic radiographic changes. Analyses were performed for the entire cohort and within subsets including by resection status and dose fractionation. A total of 178 lesions in 143 patients were included. Targets with volume diameters measuring at least 2 cm were used. Median follow-up was 2.3 years. Overall survival at 1 and 2 years was 56% and 32%, respectively. Most lesions (n = 119) were resected and treated with SRS post-operatively. The most common dose and fractionation schemes used were 30 Gy in 5 fractions (n = 89) and 27 Gy in 3 fractions (n = 63). For the entire cohort, the cumulative incidence of LP 1 and 2 years was 26% and 34%, respectively. The cumulative incidence of radiographic radionecrosis at 1 and 2 years was 12% and 17%, respectively. There was no difference in LP or RN between 27 Gy in 3 fractions versus 30 Gy in 5 fractions (p>0.5 for both). Median planning target volume (PTV) size was 18.5 cc for the 27 Gy in 3 fraction group compared to 21.9 cc in the 30 Gy in 5 fraction group. Minimum or maximum dose within the target was not associated with increased risk of LP or RN. Among patients receiving 27 Gy in 3 fractions, patients treated with resection followed by SRS had lower risk of LP compared to those treated with SRS alone (HR: 0.15, 95% CI: 0.03-0.64, p = 0.011). Among patients receiving 30 Gy in 5 fractions, patients who received corticosteroids prior to SRS had a lower risk of RN (HR: 0.14, 95% CI: 0.03-0.66, p = 0.013). For the entire cohort as well as within all subgroups, PD-L1≥1% was associated with increased risk of RN (p<0.001 for all). Selecting the optimal SRS dose fractionation and planning parameters to minimize both LP and RN remains a challenge for large targets. In this analysis, 27 Gy in 3 fractions appeared to provide equivalent LP and RN compared to 30 Gy in 5 fractions, and may be more convenient for patients. Patients with PD-L1≥1% with large brain targets treated with SRS may be at increased risk of RN; corticosteroid prophylaxis may be considered in this population.

Stereotactic Radiosurgery for Trigeminal Neuralgia: A Comparison of Proximal and Distal Isocenter Outcomes

Trigeminal neuralgia is a chronic pain condition of the trigeminal nerve affecting 12 per 100,000 people. Stereotactic radiosurgery (SRS) delivered by both a non-invasive stereotactic radiosurgery instrument and linear accelerators (LINAC) is a non-invasive alternative to surgical approaches. Although SRS in this setting is commonly performed, there lacks a consensus and comparative data on the optimal anatomical target with the two most common targets being the dorsal root entry zone (proximal) and retrogasserian zone (distal). This study aims to evaluate treatment outcomes in patients based on these two target locations. This multi-center, retrospective analysis included patients treated for trigeminal neuralgia between 2017 and 2021 with GK and LINAC-based SRS who were followed for at least 1 year. All patients received a dose of 85 Gy prescribed to the isocenter, set at the dorsal root entry zone (proximal) or the retrogasserian zone (distal). Isocenter location was based on the preference of the radiation oncologist and neurosurgeon. Patient reported clinical pain relief was recorded as full, partial, or no pain relief after SRS. Among patients with full and partial pain relief duration of pain relief was recorded. Ability to achieve full or partial medication de-escalation was also recorded. Outcomes of patients in the proximal and distal target cohort were compared using time based univariate analyses using log rank hazards model. We identified 86 eligible patients, of whom 54 patients (63%; median age 63, 72% female) were treated using a proximal target, and 32 (37%; median age 66, 71% female) were prescribed to a distal target. In the proximal and distal cohorts, patients experienced pain relief (either partial or full relief) at a rate of 74% and 90% and full pain relief at a rate of 46% and 31%, respectively (p = 0.011). The duration of pain relief was not significantly different amongst the two groups (p = 0.18). Partial medication de-escalation was more frequent in the distal target (75%) vs proximal (33%), while full medication de-escalation was more frequent with proximal (39%) vs distal (13%), p = 0.001. This study contributes to the limited data evaluating the differences in outcomes between proximal and distal targeting for treatment of trigeminal neuralgia with stereotactic radiosurgery. Overall, this study confirms that both approaches achieve a high rate of response in a difficult to control disease process. Our study suggests that a distal isocenter may be associated with higher rates of any type of pain improvement while a proximal isocenter may be associated with higher rates of complete pain relief. This data is hypothesis-generating and warrants further investigation into the effectiveness/toxicity differences of two approaches.

Frameless LINAC-Based Stereotactic Radiosurgery is Safe and Effective for Essential and Parkinsonian Tremor

Stereotactic radiosurgery (SRS) to the thalamus is an ablative technique used for treatment of refractory tremor of essential or Parkinsonian origin. Because of the high dose, small target, and required precision, framed SRS on the Gamma Knife has been the historical platform of choice. We tested our recently developed technique to emulate GK dose distributions on a multi-leaf collimator (MLC)-equipped linear accelerator (LINAC) without cumbersome, inefficient cones in a prospective trial of safety and efficacy. We quantified pre-treatment contralateral tremor according to FTM scoring system. We obtained MPRAGE, FGATIR, DTI, and RS-fMRI sequences. We identified the VIM via classical stereotactic reference location and connectomically, and then targeted it to 135 Gy dmax in a manner dosimetrically roughly equivalent to 4 mm GK shot. We adjusted each target such that the 25 Gy isodose line did not overlap the posterior limb of the capsule. We immobilized patients in a highly rigid thermoplastic mask and delivered treatment on an Edge™ LINAC with HDMLC. Intrafraction optical surface monitoring (OSMS) ensured patient immobility. We surveilled post-treatment imaging and recorded tremor scoring, QOL outcomes, and adverse events. We accrued 42 patients (16 female, 26 males; median age 72.5) over 36 months. 38 had essential tremor, 4 had tremor-dominant Parkinson's; 2 withdrew prior to treatment. Ten patients were on therapeutic anti-coagulation, and were not required to discontinue. At time of submission 39 patients had follow-up ≥ 6 months. 35/39 (89.7%) exhibited clinically meaningful tremor reduction. Mean limb tremor reduction among responders was 43.5% (range: 9 - 100%). Time to patient-reported tremor improvement was 0.3 to 15 months. One patient experienced Gr 3, and 4 patients experienced Gr 1-2 toxicity. MLC-based SRS thalamotomy is safe and effective for refractory tremor treatment. Multidisciplinary management is key for proper patient selection, treatment, and monitoring. Our outcomes appear congruent to historical GK controls as well as more modern MRgFUS outcomes.

Patient-Reported Cognitive Outcomes and Survival after Stereotactic Radiosurgery for 15 or More Brain Metastases

Overall survival (OS) in metastatic cancer patients has been improving with continued advancements, necessitating greater attention to treatment related toxicities. Patients with ≥ 15 brain metastases (BM) continue to be treated with whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery (SRS), with the aim of evaluating safety, cognitive outcomes, and survival metrics. Patients who received SRS for ≥ 15 BMs in 1-5 fractions from 2014-2022 using the previously described single isocenter multi-target technique were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS) scores. Kaplan-Meier method was used for survival analysis and log-rank test was used for intergroup comparisons. A total of 118 patients underwent 124 courses of LINAC-based SRS. The mean and median number of lesions treated per patient was 24.8 and 20, respectively (range 15 - 94). Most common primary histologies were lung (47.6%), melanoma (21.0%), and breast (14.5%). The median SRS dose was 24 Gy (range 18 - 30 Gy) with 87.9% receiving 3 fraction SRS. At the time of SRS, 19.4% patients had received prior WBRT and 24.2% had received at least one prior SRS course. The rate of any grade radiation necrosis (RN) and ≥ grade 3 RN were 15.3% and 3.2% respectively. New onset seizures were seen in 2.4%, alopecia in 2.4%, and subjective cognitive decline in 4% of patients. Median follow-up by reverse Kaplan-Meier method was 17.8 months (m). Cognitive data was available for 38 patients. Mean PROMIS scores at baseline, 3m, 6m and 9m after SRS were 32.0, 31.6, 30.4 and 28.7 out of 40, respectively. When longitudinal trends were available, 25 of 31 patients had a stable or improved PROMIS score. The 12m local control was 97.6%. Cumulative incidence of distant intracranial failure was 79.2%. One year freedom from neurological death, leptomeningeal disease, and salvage WBRT were 85.6%, 87.6% and 71.7% respectively. Median OS from brain metastases diagnosis was 11.3m (95% CI 7.2m - 15.3m) overall, while it was 9.2m (6.5 - 11.8m) after excluding patients who had prior WBRT or SRS (n = 79). One-year survival was 40% from diagnosis and 38.7% from SRS. On Cox regression analysis, prior WBRT (p = 0.002), higher KPS (p = 0.050), systemic therapy after SRS (p<0.001), and controlled extracranial disease (p = 0.007) predicted for improved OS. We present here the largest study evaluating SRS for patients with ≥ 15 BMs. We found that SRS was safe, had favorable cognitive outcomes, and comparable survival outcomes to contemporary studies evaluating WBRT in this patient population. Treatment-naïve patients had a median survival of > 6 months, long enough to benefit from cognitive sparing with SRS. Our study supports further randomized studies comparing SRS and memory avoidance WBRT approaches for patients with ≥ 15 BMs.

Impact of Concurrent Targeted Therapy and Immunotherapy on the Incidence of Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases

The management of metastatic disease has evolved with the advent of immunotherapy (IT) and targeted therapies (TT). Yet, there is limited understanding of the toxicity associated with combining these agents with stereotactic radiosurgery (SRS). We retrospectively evaluated the impact of concurrent systemic therapy (ST) on the risk of radiation necrosis (RN) following LINAC-based SRS for brain metastases (BM). A retrospective study was conducted within an integrated health care system from March 2017 to December 2021 of 313 patients who underwent SRS or fractionated SRS in 3 or 5 treatments to a total of 1,644 intact BM. Post-operative cavity SRS and re-irradiated lesions were excluded. RN was diagnosed using perfusion MRI, contrast clearance MRI, or serial standard MRI and graded using CTCAE (v.5). Concurrent ST was defined as administration within 1 month preceding or following SRS. Overall survival (OS) and risk of RN were estimated by the Kaplan-Meier method. Logistics regression analyses were performed to compare risk of RN in patients who received concurrent systemic therapy to those who did not, adjusted for PTV volume and receipt of whole brain radiotherapy (WBRT). Median follow-up was 12.2 months. Median age was 64 years (range: 24-92). Primary sites per patient included lung (48.9%), breast (18.2%), melanoma (11.5%), kidney (6.1%), and other (15.3%). Median total lesions treated was 3 (range: 1-44); 65.9% of patients underwent 1 course of SRS, 23.4% underwent 2 courses, 6.2% underwent 3 courses, 4.5% underwent >4 courses. Seventy-six (24.2%) patients received WBRT. Overall, 70.6% of lesions received concurrent ST including chemotherapy (CT) (32.5%), IT (26.8%), and TT (27.6%); 16.4% received a combination of ST. Median OS was 12.9 months (95% CI: 10.4-15.5). RN was observed in 50 (3.0%) lesions in 42 (13.4%) patients. The 1-year risk of RN was 4.0% per lesion and 15.4% per patient. Symptomatic RN (SRN) was observed in 31 (1.9%) lesions in 24 (7.7%) patients. The 1-year risk of SRN was 2.7% per lesion and 10.1% per patient. When compared to lesions treated without concurrent systemic therapy, there was no increased risk of RN observed in lesions treated with concurrent CT (adjusted OR = 0.86 (95% CI: 0.43-1.73) p = 0.68), concurrent IT (adjusted OR = 0.84 (95% CI: 0.41-1.71) p = 0.84), or concurrent TT (adjusted OR = 0.57 (95% CI: 0.25-1.30) p = 0.18). Treatments of SRN included dexamethasone (96.8%), bevacizumab (22.6%), and laser interstitial thermal therapy (6.5%). Concurrent IT and TT appears well-tolerated in patients who undergo SRS for treatment of BM. No increased risk of RN was observed in lesions treated with concurrent IT or TT compared to lesions treated in the absence of concurrent ST. Further prospective and agent-specific evaluation is necessary to confirm these findings.

Presence of Activated (Phosphorylated) STAT3 in Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases.

Brain radiation necrosis (RN) is a subacute or late adverse event following radiotherapy, involving an exacerbated inflammatory response of the brain tissue. The risk of symptomatic RN associated with stereotactic radiosurgery (SRS) as part of the treatment of brain metastases (BMs) has been a subject of recent investigation. The activation of the signal transducer and activator of transcription 3 (STAT3) was shown in reactive astrocytes (RA) associated with BMs. Given that the pathophysiological mechanisms behind RN are not fully understood, we sought to investigate the role of STAT3 among other inflammatory markers in RN development. A mouse model of RN using clinical LINAC-based SRS was designed to induce brain necrosis with the administration of 50 Gy in a single fraction to the left hemisphere using a circular collimator of 5 mm diameter. Immunohistochemistry and multiplex staining for CD4, CD8, CD68, GFAP, and STAT3 were performed. For validation, eleven patients with BMs treated with SRS who developed symptomatic RN and required surgery were identified to perform staining for CD68, GFAP, and STAT3. In the mouse model, the RN and perinecrotic areas showed significantly higher staining for F4/80+ and GFAP+ cells, with a high infiltration of CD4 and CD8 T-lymphocytes, when compared to the non-irradiated cerebral hemisphere. A high number of GFAP+pSTAT3+ and F4/80+pSTAT3+ cells was found in the RN areas and the rest of the irradiated hemisphere. The analysis of human brain specimens showed that astrocytes and microglia were actively phosphorylating STAT3 in the areas of RN and gliosis. Phosphorylated STAT3 is highly expressed in the microglia and RA pertaining to the areas of brain RN. Targeting STAT3 via inhibition represents a promising strategy to ameliorate symptomatic RN in BM patients undergoing SRS.

STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM GASTROINTESTINAL PRIMARIES: ANALYSIS OF OUTCOMES

Abstract AIMS Brain metastases from gastrointestinal primaries are uncommon with poor reported outcomes following SRS. We evaluated clinical outcomes for patients diagnosed with metastatic brain tumours from a gastrointestinal primary treated with stereotactic radiosurgery (SRS). METHOD A single institutional retrospective review of patients treated with LINAC-based SRS at our institution between 2017 and 2022. Median survival was calculated from the time of SRS. RESULTS A total of 24 patients were treated with primary malignancy locations as follows: 10 colon, 7 rectum and 7 oesophageal. Median survival was 6.4 months for the overall cohort and 4.5 months for colon, 6.1 months for rectum and 14 months for oesophagus. 44% and 14% of patients had undergone surgical resection with colorectal cancer (CRC) and oesophageal cancer respectively. Median survival in CRC patients receiving SRS post-operatively was 6.8 months compared with 11.5 months for patients with non-gastrointestinal primaries. Time from diagnosis of the primary malignancy to diagnosis of brain metastases showed an inverse correlation with survival: 48 months colon, 21 months rectum and 13 months oesophagus. Compared to oesophageal patients, CRC patients were more likely to have extra-cranial disease at the time of SRS (57% vs. 18%). CONCLUSIONS Survival after SRS to brain metastases from gastrointestinal primaries is poor, but we demonstrate important differences in outcome depending on the location of the primary malignancy. Oesophageal cancer patients had the best survival with colon cancer patients having the worst. Although our findings are likely to influenced by patient selection bias, these differences are worthy of further investigation.

Correlation Between Post-Radiosurgery Perinidal Hyperintensity and AVM Obliteration Following LINAC-Based Stereotactic Radiosurgery

We studied the correlation between new-onset perinidal hyperintensity (PH) on T2-weighted magnetic resonance imaging and obliteration of intracranial arteriovenous malformation (AVM) after stereotactic radiosurgery (SRS). A retrospective study of 148 patients with an intracranial AVM who underwent SRS between September 2005 and June 2018 and had ≥1 radiological follow-up (early magnetic resonance imaging) 12-18 months after SRS was performed to analyze the correlation between PH (graded from 0 to 2) and AVM obliteration. Of the 148 patients, 95 were male. The mean patient age was 27.7 ± 12.4 years. Of the 148 AVMs, 105 (70.9%) were obliterated at a median follow-up of 27 months (interquartile range, 14-48 months). The cumulative 3-, 5-, 10-year obliteration rate was 51.8%, 70.8%, and 91.8%, respectively. New-onset PH was observed in 58 AVMs (39.2%; 50 obliterated and 8 not obliterated). No association was found between the pretreatment variables or dose delivered and the development of PH. Grade 2 PH was associated with the risk of symptoms developing compared with grade 1 PH (37.5% vs. 4%; P= 0.002). Symptomatic PH was more likely to develop in patients with a larger AVM (P= 0.05). On multivariate analysis, the presence of a single draining vein (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.8), a lower median AVM volume (OR, 0.97; 95% CI, 0.6-0.89), a mean marginal radiation dose (OR, 1.29; 95% CI, 1.02-1.64), and the presence of PH (OR, 3.16; 95% CI, 1.29-7.71) were independent predictors of AVM obliteration. The incidence of PH after SRS for AVM was 39.2%. PH was an independent predictor of AVM obliteration after SRS. Grade 2 PH and a larger AVM volume were associated with symptomatic PH.

Gantry triggered x-ray verification during single-isocenter stereotactic radiosurgery: Increased certainty for a no-margin strategy

BackgroundSingle-isocenter linac-based stereotactic radiosurgery (SRS) has emerged as a dedicated treatment option for multiple brain metastases. Consequently, image-guidance for patient positioning and motion management has become very important. The purpose of this study was to analyze intra-fraction errors measured with stereoscopic x-rays and their impact on the dose distribution. Materials and methodsTreatments were planned with non– coplanar dynamic conformal arcs for 33 patients corresponding to 127 brain lesions and 356 arcs. Intra-arc positioning errors were measuredusing stereoscopic x-rays (ExacTrac Dynamic, Brainlab), triggered during arc delivery. Couch corrections above 0.7 mm and 0.5° were always applied. Intra-arc positioning data was analyzed. The dose impact was evaluated by applying the measured errors to the dose given in each arc. ResultsMedian residual errors were 0.10 mm, 0.13 mm and 0.08 mm for the lateral, longitudinal and vertical directions and 0.10°, 0.08° and 0.13° for the pitch, roll and yaw angles respectively. 90% of the treatment arcs showed shifts of less than 0.4 mm and 0.4°in all directions. Dosimetric impact of motion showed the largest losses in coverage on small targets. All targets achieved at least 95% of the prescription dose to 95% of their volume, even when planned without margins. ConclusionsIntra-fractional errors measured during beam delivery were found to be notably low with a dose impact that showed acceptable target coverage when applying these intra-arc errors to the dose distributions of the individual treatment arcs. Using an adequate immobilization and intra-fraction imaging prior to and during irradiation, no margins need to be added to compensate for intra-fraction motion.