Single-session Stereotactic Radiosurgery Research Articles

Stereotactic radiosurgery for haemorrhagic cerebral cavernous malformation: a multi-institutional, retrospective study

BackgroundCerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The...

Characterization of Pediatric Infratentorial Arteriovenous Malformations: A Retrospective, Multicenter Cohort Study.

Infratentorial arteriovenous malformations (AVMs) harbor different characteristics compared with supratentorial AVMs. This study aims to explore the unique characteristics of pediatric infratentorial AVMs and their response to single session stereotactic radiosurgery (SRS). The International Radiosurgery Research Foundation database of pediatric patients with AVM (age <18 years) who underwent SRS was retrospectively reviewed. Baseline demographics, AVM characteristics, outcomes, and complications post-SRS were compared between infratentorial and supratentorial pediatric AVMs. Unfavorable outcome was defined as the absence of AVM obliteration, post-SRS hemorrhage, or permanent radiation-induced changes at last follow-up. A total of 535 pediatric AVMs managed with SRS with a median follow-up of 67 months (IQR 29.0-130.6) were included, with 69 being infratentorial and 466 supratentorial. The infratentorial group had a higher proportion of deep location (58.4% vs 30.3%, P = <.001), deep venous drainage (79.8% vs 61.8%, P = .004), and prior embolization (26.1% vs 15.7%, P = .032). There was a higher proportion of hemorrhagic presentation in the infratentorial group (79.7% vs 71.3%, P = .146). There was no statistically significant difference in the odds of an unfavorable outcome (odds ratio [OR] = 1.36 [0.82-2.28]), AVM obliteration (OR = 0.85 [0.5-1.43]), post-SRS hemorrhage (OR = 0.83 [0.31-2.18]), or radiologic radiation-induced changes (OR = 1.08 [0.63-1.84]) between both cohorts. No statistically significant difference on the rates of outcomes of interest and complications were found in the adjusted model. Despite baseline differences between infratentorial and supratentorial pediatric AVMs, SRS outcomes, including AVM obliteration and post-SRS hemorrhage rates, were comparable amongst both groups. SRS appears to have a similar risk profile and therapeutic benefit to infratentorial pediatric AVMs as it does for those with a supratentorial location.

Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.

Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses. Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3cm, 15 Gy for >3-4cm, and 12 Gy for >4-6cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. A total of 35 patients/36 lesions were enrolled. For tumor size >2-3cm, patients were enrolled up to the second dose level (21 Gy); for >3-4cm and >4-6cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3cm was not reached; and was 18 Gy for both >3-4cm arm and >4-6cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%. Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

1133 Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery

INTRODUCTION: Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biologic effective dose (BED) is recognized as a predictive variable for outcomes in the adult population, but its role has never been studied in pediatric outcomes. METHODS: Retrospective data for = 18 years old patients treated with single-session SRS for AVM was collected from 1989 – 2019. BED calculations were performed using an a/b ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using two models (margin dose versus BED). RESULTS: One-hundred-ninety-seven patients [median age = 13.1 years, Interquartile range (IQR) = 5.2] were included; 72.6% presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQ = 4.0) with a median BED of 183.2Gy (IQR = 70.54) was used to treat AVMs with a median volume of 2.8 cm3 (IQR = 2.9). Following SRS, obliteration was confirmed in 115 patients (58.4%) using MRI and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+=2.2-67.4), 66.0% (95% CI= 56.0-73.7) at 3, 5 and 10 years respectively. In multivariate analysis, a BED &gt;180 Gy [HR = 2.11, 95% CI=1.30-3.40, p = 0.002] in model 1, and a margin dose &gt;20 Gy [HR = 1.90, 95% CI = 1.15-3.13, p = 0.019] in model 2, were associated with obliteration. An AVM nidus volume &gt;4 cm3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose were associated with RIC occurrence, with the only predictive factor being deep AVM location [HR = 3, 95% CI = 1-9.1, p = 0.048]. CONCLUSIONS: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Third Stereotactic Radiosurgery for Residual Arteriovenous Malformations: A Retrospective Multicenter Study

BACKGROUND AND OBJECTIVES: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual. METHODS: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC. RESULTS: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up. CONCLUSION: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs.

Hypofractionated stereotactic radiotherapy in Spetzler Martin grades 4 and 5 arteriovenous malformations in the pediatric population: Is it a viable alternative?

To analyze the outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for Spetzler Martin grades 4 and 5 arteriovenous malformations (AVMs) in a pediatric population. Fourteen patients with Spetzler Martin (SM) grades IV and V large AVMs who underwent HFSRT between January 2013 and July 2019 were retrospectively reviewed. All patients received HFSRT at a dose of 30-36Gy in 5 to 6 fractions. They were followed up annually with clinical and imaging assessments to evaluate obliteration rates. The median age at presentation was 15years (range 8-21years). Ten (71%) were SM grade 4 AVMs and the rest were SM grade 5 AVMs. The majority presented with headache (8 [57%]), and 3 (21%) presented with bleeding. The median nidus volume was 39.4cc (IQR, 31.4-52.4). Two (14%) patients had infratentorial AVMs. All of them had deep venous drainage. The median clinical follow-up duration was 75months (range 31-107months). There was complete obliteration of the nidus in 3 (21%) patients with a median time to obliteration of 39months. HFSRT resulted in a reduction of the AVM volume to 12cc or less in nearly 70% of patients. None of the patients experienced re-bleeding. 79% reported an improvement in their symptoms. HFSRT is a highly effective treatment for high-grade AVMs in children, which can result in either complete elimination or significant reduction of the nidus volume or make it suitable for additional treatment, such as single-session stereotactic radiosurgery (SRS).

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

The Role of Stereotactic Radiosurgery in Patients With Brain Metastases From Colorectal Cancers.

The role of stereotactic radiosurgery (SRS) in patients with brain metastases (BMs) from colorectal cancers (CRCs) has not been established. The authors present a single-institution experience of patients with CRC who underwent SRS with metastatic brain spread. We retrospectively analyzed 111 patients with metastatic CRC (64 female, 57.7%), with 449 BMs treated with Gamma Knife SRS between 2000 and 2022. The median age during SRS was 63 years (range: 28-86), and the median Karnofsky Performance Scale was 80 (range: 60-100). The primary sites were colon (85 patients, 76.6%) and rectal (26 patients, 23.4%). Three patients underwent hypofractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27-30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 13-20). The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (88.3%) patients expired at last follow-up and 15 patients (15.3%) died related to progressive intracranial disease. A Karnofsky Performance Scale of <80 at SRS presentation ( P = .02, hazard ratio [HR]: 0.6, 95% CI: 0.4-0.9) and no previous surgical resection ( P < .01, HR: 0.4, 95% CI: 0.3-0.7) were associated with inferior overall survival using multivariate analysis. Seventeen patients (15.3%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.4%) developed new BMs at a median of 5 months (range: 2-26) between SRS and new tumor detection. Less than three BMs at SRS presentation ( P = .02, HR: 2.6, 95% CI: 1.2-5.6) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.4%. SRS effectively controls BMs from CRC with low risk of treatment-related toxicity. During follow-up, the development of additional metastases can be safely treated by repeat SRS.

Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery.

Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biological effective dose (BED) has shown promising results in 2 previous studies as a predictive variable for outcomes in adults, but its role has never been studied in pediatric outcomes. Retrospective data for patients 18 years or younger treated with a single-session SRS for AVMs were collected from 1989 to 2019. BED calculations were performed using an α/β ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using 2 models (margin dose vs BED). One hundred ninety-seven patients (median age = 13.1 years, IQR = 5.2) were included; 72.6% (143/197) of them presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQR = 4.0) with a median BED of 183.2 Gy (IQR = 70.54) was used to treat AVM with a median volume of 2.8 cm 3 (IQR = 2.9). After SRS, obliteration was confirmed in 115/197 patients (58.4%) using magnetic resonance imaging and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+ = 2.2-67.4), and 66.0% (95% CI = 56.0-73.7) at 3, 5, and 10 years, respectively. In Cox multivariate analysis, a BED >180 Gy (hazard ratio [HR] = 2.11, 95% CI = 1.30-3.40, P = .002) in model 1 and a margin dose >20 Gy (HR = 1.90, 95% CI = 1.15-3.13, P = .019) in model 2 were associated with obliteration. An AVM nidus volume >4 cm 3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose was associated with RIC occurrence, with the only predictive factor being deep AVM location (HR = 3, 95% CI = 1-9.1, P = .048). This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Characterization of Large Brain Metastases with 18F-Fluciclovine PET/CT Treated with Staged Stereotactic Radiosurgery (SSRS): Phase 1 Proof-of-Concept Interim Analysis

Single-session stereotactic radiosurgery (SRS) for large brain metastases (>2cm) results in modest local control. Temporally staged SRS (SSRS), whereby 2 stages of SRS are delivered over a time interval of several weeks, is a novel strategy associated with improved control rates and acceptable radiation necrosis rates. Biomarkers for response are lacking. Here, we report interim results of a phase 1, proof-of-concept study (NCT04689048) to assess the potential clinical utility of amino acid radiotracer 18F-fluciclovine PET/CT as a functional integral biomarker for patients with large brain metastases treated with SSRS. Patients with previously untreated large brain metastases (≥1 lesion; >2cm) underwent a baseline (pre-treatment) 18F-fluciclovine PET/CT and contrast-enhanced treatment planning brain MRI immediately before first SSRS (15 Gy), an interim PET/CT + MRI (4 weeks after the 1st SSRS, immediately prior the 2nd SSRS [15 Gy]), and post-treatment PET/CT + MRI (8 weeks after 2nd SSRS). This interim analysis reviewed the imaging characteristics from static PET images acquired 10-25 minutes after 18F-fluciclovine injection, for the first 7 enrolled patients who completed baseline imaging and 5 who completed the entire treatment course. Seven patients completed baseline imaging and were treated with SSRS for 9 protocol-eligible target lesions, and an additional 25 bystander lesions were treated with SRS. The median age was 72 years and 57% were female. All lesions > 5 mm exhibited baseline increased 18F-fluciclovine uptake compared to the normal contralateral brain. The median baseline target lesion diameters and volumes were 2.16 cm (1.76-3.22 cm) and 4.71cc (2.24-10.21 cc). The median baseline SUVmax, SUVpeak, and SUVmean values were 5.78 (2.16-8.79), 3.33 (0.5-2.72), and 1.75 (1.22-5.16), respectively. The median relative reduction in diameter and volume were both 2% (-13% to 23% and -30% to 60%, respectively) at the interim scans, and at the first follow-up were 30% (-0.2% to 44%) and 43% (-13% to 94%), respectively. Corresponding median relative reduction values for SUVmax, SUVpeak, and SUVmean at interim scans were 20% (-174%-73%), 9% (-99% to 75%), and 14% (-36% to 69%), and at first follow-up 59% (21% to 87%), 41% (-11% to 86%), and 21% (-44% to 79%), respectively. Bystander lesions (< 2 cm) treated with SRS had a median baseline lesion diameter and volume of 0.5 cm (Range: 0.20-1.64 cm) and 0.06 cc (Range: 0.01-1.94 cc). Corresponding median reductions for SUVmax were 5% at interim and 63% at follow-up scans. This proof-of-concept interim study reports baseline 18F-fluciclovine metrics for patients with brain metastases of varying lesion diameters and volumes. Target lesions appear to demonstrate interval reduction in PET metrics after SSRS, more than dimensional measurements alone.

Results of a Phase I Trial of Dose Escalation for Preoperative Stereotactic Radiosurgery for Patients with Large Brain Metastases

Single session stereotactic radiosurgery (SRS) alone for brain metastases larger than 2 cm in diameter results in unsatisfactory local control. Surgical resection alone also produces unreliable local control and perioperative radiation is required. We conducted a prospective phase I trial (NCT01891318) for brain metastases greater than 2 cm to determine the safety of preoperative SRS at escalating doses followed by surgical resection. Radiosurgery dose started at RTOG 9005 dose levels for the 3 cohorts based on maximum tumor diameter of the index lesion: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy >4-6 cm. Concurrent SRS alone to other smaller lesions was allowed using standard RTOG dose. Dose limiting toxicity (DLT) was defined as grade 3 or greater acute toxicity within 3 to 4 months after SRS. Patients underwent surgical resection within 2 weeks and were followed with imaging and neurological evaluations every 3 months. A total of 35 patients were enrolled into the trial (see Table 1 below). The median age was 63, and median interval between SRS and surgery was 2 days. The most common histology was non-small cell lung cancer (57.1%), followed by breast cancer (14.3%). For tumor size >2-3 cm, patients were enrolled up to the 2nd dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the 3rd dose level (21 Gy and 18 Gy, respectively) was reached. There was a total of 3 DLTs: 2 in the >3-4 cm cohort and 1 in the >4-6 cm cohort (Table 1). The maximum tolerable dose (MTD) was 18 Gy (2nd dose level) for >3-4 cm, and 18 Gy (3rd dose level) for >4-6 cm. With a median follow-up of 64 months, the 6- and 12-month local control rates were 88.8% and 79.1%, respectively. The 6- and 12-month distant brain control was 63.1% and 55.3%, respectively. Overall survival at 6 and 12 months was 82.9% and 59.0%. The rate of leptomeningeal disease (LMD) at 2 years was 0%. Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size results in local control comparable to postoperative SRS or whole-brain radiation therapy and demonstrates acceptable acute toxicity. The Phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

Single-session stereotactic radiosurgery for large perioptic meningiomas.

Meningiomas close to the optic pathway are commonly candidates for microsurgical decompression, more so if they are large perioptic meningiomas. However, microsurgery itself imposes risk to vision, and the larger the tumor, the more the risk and the lower the possibility of postoperative visual recovery. Fractionated stereotactic radiotherapy is usually reserved for such cases. The purpose of this study was to assess the long-term efficacy and safety of single-session stereotactic radiosurgery (SRS) for large (≥ 10 cm3) perioptic intracranial benign meningiomas. This retrospective study included 175 patients with large perioptic benign meningiomas (≥ 10 cm3) who were treated by single-session SRS. Perioptic meningiomas were defined as meningiomas touching, compressing, or within 3 mm of the optic pathway. The median tumor volume was 15 cm3 (range 10-57.3 cm3, IQR 8.4 cm3). The median prescription dose was 12 Gy (range 9-14 Gy, IQR 1 Gy). The median follow-up period was 72 months (range 13-217 months, IQR 65 months). The tumor control rate was 92%. The progression-free survival rates at 5 and 10 years were 97% and 80%, respectively. Favorable (better/stable) visual outcome was reported in 169 patients (97%) and unfavorable (worse) outcome in 6 patients (3%). Temporary adverse radiation effects were observed in 21 patients (12%), but only 7 patients (4%) were symptomatic. Sixty-three patients had a blind/nonuseful eye according to the pretreatment visual field examination. Visual improvement was observed in the blind/nonuseful eye in 17 patients (27%), while vision remained unchanged in 46 patients (73%). Ocular nerve palsy improved in 36 patients (61%). Tumor shrinkage was not a prerequisite for cranial nerve improvement. SRS provides an effective and safe treatment option for large perioptic meningiomas.

LMAP-19 THE ROLE OF STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES FROM COLORECTAL CANCERS

Abstract BACKGROUND AND OBJECTIVES The role of stereotactic radiosurgery (SRS) for patients with brain metastases from colorectal cancers (CRC) has not been established. The authors present a single-institution experience of CRC patients who underwent SRS with metastatic brain spread. METHODS We retrospectively analyzed 112 metastatic CRC patients (64 female, 57.14%) with 450 brain metastases that were treated with Gamma Knife SRS between 2000-2022. The median age at SRS was 63 years (range: 28-86) and the median Karnofsky Performance Score (KPS) was 80 (range: 60-100). The primary sites were colon (86 patients, 76.79%) and rectal (26 patients, 21%). Three patients underwent hypo-fractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27- 30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 11-20). RESULTS The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (87.5%) patients expired at last follow up and 15 patients (15.31%) died related to progressive intracranial disease. KPS &amp;lt; 80 at SRS presentation (p=0.03, HR: 0.63, 95% CI: 0.41-0.96) was associated with inferior overall survival using multivariate analysis. Seventeen patients (15.18%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.21%) developed new brain metastases at a median of 5 months (range: 2-26) between SRS and new tumor detection. KPS ≥ 80 (p=0.05, HR: 0.96, 95% CI: 0.93-0.99), and &amp;lt; 3 brain metastases at SRS presentation (p&amp;lt;0.01, HR: 3.62, 95% CI: 1.53-8.56) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.36%. CONCLUSIONS SRS effectively controls brain metastases from CRC with a low risk of treatment-related toxicity, allowing patients to focus on primary disease management. During follow-up, the development of progressive or additional metastases can be safely treated by repeat SRS.

Volumetric Assessment of Nonfunctional Pituitary Adenoma Treated With Stereotactic Radiosurgery: An Assessment of Long-Term Response.

Stereotactic radiosurgery (SRS) is widely used to manage recurrent or residual nonfunctioning pituitary adenomas (NFPAs). Studies on the long-term volumetric response of NFPAs to SRS are lacking. Such a post-SRS volumetric study will allow us to set up appropriate radiographic follow-up protocols and predict tumor volumetric response. Two providers independently performed volumetric analyses on 54 patients who underwent single-session SRS for a recurrent/residual NFPA. In the case of discrepancy between their results, the final volume was confirmed by an independent third provider. Volumetry was performed on the 1-, 3-, 5-, 7-, and 10-year follow-up neuroimaging studies. Most patients showed a favorable volumetric response, with 87% (47/54) showing tumor regression and 13% (7/54) showing tumor stability at 10 years. Year 3 post-SRS volumetric results correlated (R 2 = 0.82, 0.63, 0.56) with 5-, 7-, and 10-year outcomes. The mean interval volumetric reduction was 17% on year 1; further interval volumetric reduction was 17%, 9%, 4%, and 9% on years 3, 5, 7, and 10, respectively. Year 3 post-SRS volumetric response of patients with residual or recurrent NFPAs is predictive of their 7-10-year follow-up response. For patients demonstrating NFPA regression in the first 1-3 years, interval follow-up MRI's can likely be performed at 2-year periods unless otherwise clinically indicated. Further studies are needed to better define the volumetric response to adenomas more than a decade after SRS.

Vestibular Schwannoma Stereotactic Radiosurgery in Octogenarians: Case Series.

The management of octogenarians with vestibular schwannomas (VS) has received little attention. However, with the increase in octogenarian population, more effort is needed to clarify the value of stereotactic radiosurgery (SRS) in this population. The aim of this study was to evaluate the safety and efficacy of SRS in this patient age group. A retrospective study of 62 patients aged 80 years or older who underwent single-session SRS for symptomatic VS during a 35-year interval was performed. The median patient age was 82 years, and 61.3% were male. SRS was performed as planned adjuvant management or for delayed progression after prior partial resection in 5 patients. SRS resulted in a 5-year tumor control rate of 95.6% with a 4.8% risk of adverse radiation effects (ARE). Tumor control was unrelated to patient age, tumor volume, Koos grade, sex, SRS margin dose, or prior surgical management. Four patients underwent additional management including 1 patient with symptomatic progression requiring surgical resection, 2 patients with symptomatic hydrocephalus requiring cerebrospinal fluid diversion, and 1 patient whose tumor-related cyst required delayed cyst aspiration. Three patients developed ARE, including 1 patient with permanent facial weakness (House-Brackmann grade II), 1 who developed trigeminal neuropathy, and 1 who had worsening gait disorder. Six patients had serviceable hearing preservation before SRS, and 2 maintained serviceable hearing preservation after 4 years. A total of 44 (71%) patients died at an interval ranging from 6 to 244 months after SRS. SRS resulted in tumor and symptom control in most octogenarian patients with VS.

Quantitative Analysis of Parenchymal Effects and Flow of Large Arteriovenous Malformations Managed With Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume-response and dose-response models have been used to predict such effects. To understand radiological outcomes and their hemodynamic effects on the regional brain. A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins. Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio ( P = .024), longer transit time ( P = .05), higher mean dose ( P = .028), and higher D95 ( P = .036). Transit times and vessel diameters are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.

Single-Session Gamma Knife Radiosurgery for Patients With 20 or More Brain Metastases.

Stereotactic radiosurgery (SRS) is a widely accepted treatment modality for brain metastases. The role of SRS in patients with higher numbers of metastases remains controversial. To define outcomes in patients with ≥20 brain metastases managed using single-session SRS. This single-institution retrospective cohort study studied 75 patients (26 non-small-cell lung cancer, 21 small-cell lung cancer, 14 breast cancer, and 14 melanoma) undergoing single-session SRS. The median number of tumors per patient was 24, and the median cumulative tumor volume was 3.70 cc. The median margin dose prescribed to each individual tumor was 16 Gy. The median integral cranial dose was 5492 mJ. The median beam on time was 160 minutes. Univariate and multivariate analyses were performed with significance set at P < .05. The median overall survival after SRS was 8.8 months (patients with non-small-cell lung cancer), 4.6 months (patients with small-cell lung cancer), 11.3 months (patients with breast cancer), and 4.1 months (patients with melanoma). Primary cancer type, number of brain metastases, and concurrent immunotherapy were significant factors in predicting survival. Local tumor control rate per patient was 97.3% and 94.6% at 6 and 12 months after SRS, respectively. Thirty-six patients underwent additional SRS for new tumor development with a median time after SRS of 5 months. Three patients experienced adverse radiation events. Single-session SRS is a well-tolerated palliative treatment option even in patients with ≥20 brain metastases, achieving local control rate >90% with low risks of neurotoxicity while continuing concurrent systemic oncological care.

Up-front single-session radiosurgery for large brain metastases-volumetric responses and outcomes.

Patients presenting with large brain metastases (LBM) pose a management challenge to the multidisciplinary neuro-oncologic team. Treatment options include surgery, whole-brain or large-field radiation therapy (WBRT), stereotactic radiosurgery (SRS), or a combination of these. To determine if corticosteroid therapy followed by SRS allows for efficient minimally invasive care in patients with LBMs not compromised by mass effect. We analyzed the change in tumor volume to determine the efficacy of single-session SRS in the treatment of LBM in comparison to other treatment modalities. Twenty-nine patients with systemic cancer and brain metastasis (≥ 2.7cm in greatest diameter) who underwent single-session SRS were included. Among 29 patients, 69% of patients had either lung, melanoma, or breast cancer. The median initial tumor size (maximal diameter) was 32mm (range 28-43), and the median initial tumor volume was 9.56 cm3 (range 1.56-25.31). The median margin dose was 16Gy (range 12-18). The average percent decrease in tumor volume compared to pre-SRS volume was 55% on imaging at 1-2months, 58% at 3-5months, 64% at 6-8months, and 57% at > 8months. There were no adverse events immediately following SRS. Median corticosteroid use after SRS was 21days. Median survival after radiosurgery was 15months. Initial high-dose corticosteroid therapy followed by prompt single-stage SRS is a safe and efficacious method to manage patients with LBMs (defined as ≥ 2.7cm).

Hypo-fractionated Gamma Knife Radiosurgery for Intra-cranial Pathologies: A Single-Center Prospective Analysis of Feasibility, Safety, Efficacy, and Complication Profile.

Single-session stereotactic radiosurgery (SRS) is a proven and effective treatment modality for various benign, malignant, and functional intra-cranial pathologies. In certain situations, single-fraction SRS is limited because of lesion size and location. Hypo-fractionated gamma knife radiosurgery (hfGKRS) is an alternative approach for such unconventional indications. To evaluate the feasibility, efficacy, safety, and complication profile of hfGKRS with evaluation of different fractionation schemes and dosing patterns. The authors prospectively evaluated 202 patients treated with frame-based hfGKRS over a 9-year period. GKRS was administered fractionated because of either a large volume (>14 cc) or an inability to spare neighboring organs at risk from permissible radiation in single-session GKRS. The inter-fraction interval was kept at 24 hours, and the dose calculation was performed with linear quadratic equations. Patients with more than 3 years of clinical and radiological follow-up were included in prospective analysis. At pre-decided follow-up criteria, treatment effects and side effects were documented on objective scales. A total of 169/202 patients met inclusion criteria. 41% patients received treatment in three fractions, whereas 59% received two-fraction GKRS. Two patients of giant cavernous sinus hemangiomas were treated with 5 Gy in the five-fraction regimen. In patients with more than 3 years of follow-up, the obliteration rate was 88% for complex arteriovenous malformations (AVMs) treated with hfGKRS because of eloquent locations, whereas it was 62% for Spetzler-Martin grade 4-5 AVMs. For non-AVM pathologies (meningiomas, schwannomas, pituitary adenomas, paragangliomas, hypothalamic hamartomas, etc.), the 5-year progression free survival was 95%. Tumor failure was noted in 0.05% patient population. Radiation necrosis developed in 8.1% patients, and radiation-induced brain edema developed in 12% patients. It was resistant to treatment in 4% patients. No patient developed radiation-induced malignancy. Hypo-fractionation did not provide any hearing improvement in giant vestibular schwannomas. hfGKRS is a valuable standalone treatment option for candidates unsuitable for single-session GKRS. The dosing parameters need to be tailored as per the pathology and neighboring structures. It provides comparable results to single-session GKRS with an acceptable safety and complication profile.

Growth dynamics of brain metastases differentiate radiation necrosis from recurrence.

Radiation necrosis (RN) is a frequent adverse event after fractionated stereotactic radiotherapy (FSRT) or single-session stereotactic radiosurgery (SRS) treatment of brain metastases (BMs). It is difficult to distinguish RN from progressive disease (PD) due to their similarities in the magnetic resonance images. Previous theoretical studies have hypothesized that RN could have faster, although transient, growth dynamics after FSRT/SRS, but no study has proven that hypothesis using patient data. Thus, we hypothesized that lesion size time dynamics obtained from growth laws fitted with data from sequential volumetric measurements on magnetic resonance images may help in discriminating recurrent BMs from RN events. A total of 101 BMs from different institutions, growing after FSRT/SRS (60 PDs and 41 RNs) in 86 patients, displaying growth for at least 3 consecutive MRI follow-ups were selected for the study from a database of 1031 BMs. The 3 parameters of the Von Bertalanffy growth law were determined for each BM and used to discriminate statistically PDs from RNs. Growth exponents in patients with RNs were found to be substantially larger than those of PD, due to the faster, although transient, dynamics of inflammatory processes. Statistically significant differences (P < .001) were found between both groups. The receiver operating characteristic curve (AUC = 0.76) supported the ability of the growth law exponent to classify the events. Growth law exponents obtained from sequential longitudinal magnetic resonance images after FSRT/SRS can be used as a complementary tool in the differential diagnosis between RN and PD.