Adverse Radiation Effects Research Articles

LMAP-22 STEREOTACTIC RADIOSURGERY FOR PATIENTS WITH BRAIN METASTASES FROM GASTROESOPHAGEAL PRIMARY CANCERS

Abstract BACKGROUND Patients with brain metastases from gastroesophageal primary cancers have poor prognoses, and current management remains unclear. The authors present the largest single-institution experience of utilizing stereotactic radiosurgery (SRS) to treat patients with brain metastases from primary gastroesophageal cancers. METHODS A retrospective review of 71 patients (64 male, 90.14%) treated with Gamma Knife SRS from 2000 to 2022 for gastroesophageal primary cancers was conducted. Overall, 243 brain metastases were treated, and the median number of metastases per patient was 2 (range:1-21). The primary sites were esophagus (59 patients, 83.10%), gastric (7 patients, 9.86%), and gastroesophageal junction (5 patients, 7.04%). The median age at SRS was 66 years (range: 26-85), and the median KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7 cc (range: 0.27-104.76), and the median margin dose was 18 Gy (range: 11-20). RESULTS The median overall survival after SRS was 7 months (range: 1-64). At the last follow-up, 54 (76.06%) patients were deceased, and 8 (14.81%) patients died due to intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. On univariate analysis, > 2 brain metastases at SRS presentation (p=0.02, HR: 10.76, 95% CI: 1.48-78.40) was found to be the only significant predictor of local tumor progression. Ten patients (14.08%) experienced new tumor development at a median time of 4 months (range: 0-14) after SRS. On multivariate analysis, both the absence of concurrent systemic therapy (p=0.01, HR: 6.58, 95% CI: 1.55-27.0) and ≤ 2 tumors at SRS presentation (p<0.01, HR: 1.21, CI: 1.08-1.36) were found to be significant predictors of distant tumor control. The incidence of transient adverse radiation effects was 8.45%. CONCLUSIONS SRS can safely and effectively be used to treat primary gastroesophageal cancer brain metastases while allowing patients to focus on primary disease management.

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 < 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 < 3 brain metastases at SRS presentation (p<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.

Stereotactic radiosurgery for distant brain metastases secondary to esthesioneuroblastoma: a single-institution series.

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication. A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported. Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects. In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.

Case Series: Gamma Knife Radiosurgery in Brain Arteriovenous, Is It Good Enough?

Highlight: Brain AVMs are a special concern due to their inherent high risk of bleeding. Gamma Knife radiosurgery (GKRS), as one of the modality treatments, is intended to induce progressive occlusion of an AVM by using high-dose targeted radiation The result of Gamma Knife radiosurgery (GKRS) can be full obliteration, with complications because adverse radiation effects. ABSTRACT Introduction: Brain arteriovenous malformations (AVMs) are relatively uncommon. Gamma Knife radiosurgery (GKRS) is one of the AVM’s therapeutic interventions, with both advantages and disadvantages. Here, we report the results of two cases of brain AVM after GKRS. Cases: Case 1: Non-contrast head MRI imaging of a 45-year-old man with persistent left-sided headaches revealed a 1.4 x 2.5 x 2.28 cm AVM nidus in the left parasagittal frontal lobe. After a single GKRS with a 25-Gy marginal dose, the MRI contrast showed complete obliteration, with persistent perifocal edema and headache. Case 2: A 25-year-old woman with a history of generalized seizures. The angiograms revealed an AVM nidus with a diameter of 32.58 mm on her right posterior frontal lobe. After a single GKRS with a 22-Gy marginal dose, the MRI contrast showed full obliteration with large edema. The patient had presented with hemiparesis. Conclusion: In these cases, the results after GKRS were full obliteration with complications of edema, headache, and hemiparesis. We also found that complications appear to be associated with adverse radiation effects.

Stereotactic radiosurgery for patients with brain metastases from gastroesophageal cancers.

The prognosis of patients with brain metastases from gastroesophageal (GE) cancers remains unclear despite recent advances in systemic therapies. The authors present a large single-institution experience in the use of stereotactic radiosurgery (SRS). A retrospective review of 71 GE cancer patients (64 male, 90.14%) who underwent Gamma Knife SRS was conducted. Overall, 243 brain metastases were treated and the median number of metastases per patient was 2 (range:1-21). The median age at SRS was 66 years (range: 26-85) and the median treatment day KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7cc (range: 0.27-104.76) and the median single-session margin dose was 18Gy (range: 12-20). The median overall survival after SRS was 7 months (range: 1-64). At last follow up, 54 (76.06%) patients were deceased, 8 of whom (14.81%) expired secondary to their intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. Ten patients (14%) experienced new remote tumor development at a median time of 4 months (range: 0-14) after SRS. Whole-brain radiation therapy (2 patients, 20%) and repeat SRS (8 patients, 80%) were used for newly developed tumors. The incidence of transient adverse radiation effects was 8.45%. In this study, the 12-month local tumor control rate was 90%. Incidences of adverse radiation effect rates were rare. The median overall survival of 7 months indicates the poor prognosis of patients with brain spread of their GE cancer.

Frameless versus frame-based stereotactic radiosurgery for intracranial arteriovenous malformations: A propensity-matched analysis.

The frameless linear accelerator (LINAC) based stereotactic radiosurgery (SRS) has been evolving with a reduction in patient discomfort. However, there was limited evidence comparing frame-based and frameless SRS for intracranial arteriovenous malformations (AVM). We aimed to compare the treatment outcomes between frame-based and frameless LINAC SRS. This retrospective cohort compared the outcomes of frame-based LINAC SRS (1998-2009) with frameless LINAC SRS (2010-2020). The primary outcome was the obliteration rate. The other outcomes included the neurological, radiological, and functional outcomes after SRS. A matched cohort was identified by propensity scores for further comparisons. A total of 65 patients were included with a mean follow-up time of 13.2years (158.5months). There were 40 patients in the frame-based group and 25 patients in the frameless group. The overall obliteration rate was comparable (Frame-based 82.5% vs Frameless 80.0%, p=0.310) and not significantly different over time (log-rank p=0.536). The crude post-SRS hemorrhage rate was 1.5% and the incidence was 0.3 per 100 person-years. There were 67.7% of patients with AVM obliteration without new persistent neurological deficits at the last visit and 56.9% of patients with AVM obliteration without any deficits (transient or persistent) during the entire follow-up period. Four patients (8.0%) developed late onset persistent adverse radiation effects (more than 96months after SRS) among 50 patients with more than 8-year surveillance. In the propensity-matched cohort of 42 patients, there was no significant difference in AVM obliteration (Frame-based vs Frameless, log-rank p=0.984). Frameless and frame-based LINAC SRS have comparable efficacy in intracranial AVM obliteration. A longer follow-up duration may further characterize the rate of late adverse radiation effects in frameless SRS.

Low-Dose Radiosurgery for Brain Metastases in the Era of Modern Systemic Therapy.

Dose selection for brain metastases stereotactic radiosurgery (SRS) classically has been based on tumor diameter with a reduction of dose in the settings of prior brain irradiation, larger tumor volumes, and critical brain location. However, retrospective series have shown local control rates to be suboptimal with reduced doses. We hypothesized that lower doses could be effective for specific tumor biologies with concomitant systemic therapies. This study aims to report the local control (LC) and toxicity when using low-dose SRS in the era of modern systemic therapy. We reviewed 102 patients with 688 tumors managed between 2014 and 2021 who had low-margin dose radiosurgery, defined as ≤14 Gy. Tumor control was correlated with demographic, clinical, and dosimetric data. The main primary cancer types were lung in 48 (47.1%), breast in 31 (30.4%), melanoma in 8 (7.8%), and others in 15 patients (11.7%). The median tumor volume was 0.037cc (0.002-26.31 cm 3 ), and the median margin dose was 14 Gy (range 10-14). The local failure (LF) cumulative incidence at 1 and 2 years was 6% and 12%, respectively. On competing risk regression analysis, larger volume, melanoma histology, and margin dose were predictors of LF. The 1-year and 2-year cumulative incidence of adverse radiation effects (ARE: an adverse imaging-defined response includes increased enhancement and peritumoral edema) was 0.8% and 2%. It is feasible to achieve acceptable LC in BMs with low-dose SRS. Volume, melanoma histology, and margin dose seem to be predictors for LF. The value of a low-dose approach may be in the management of patients with higher numbers of small or adjacent tumors with a history of whole brain radio therapy or multiple SRS sessions and in tumors in critical locations with the aim of LC and preservation of neurological function.

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.

Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases

Preoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential benefits in adverse radiation effects (AREs) and meningeal disease (MD). However, mature large-cohort multicenter data are lacking. To evaluate preoperative SRS outcomes and prognostic factors from a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases-PROPS-BM). This multicenter cohort study included patients with BMs from solid cancers, of which at least 1 lesion received preoperative SRS and a planned resection, from 8 institutions. Radiosurgery to synchronous intact BMs was allowed. Exclusion criteria included prior or planned whole-brain radiotherapy and no cranial imaging follow-up. Patients were treated between 2005 and 2021, with most treated between 2017 and 2021. Preoperative SRS to a median dose to 15 Gy in 1 fraction or 24 Gy in 3 fractions delivered at a median (IQR) of 2 (1-4) days before resection. The primary end points were cavity local recurrence (LR), MD, ARE, overall survival (OS), and multivariable analysis of prognostic factors associated with these outcomes. The study cohort included 404 patients (214 women [53%]; median [IQR] age, 60.6 [54.0-69.6] years) with 416 resected index lesions. The 2-year cavity LR rate was 13.7%. Systemic disease status, extent of resection, SRS fractionation, type of surgery (piecemeal vs en bloc), and primary tumor type were associated with cavity LR risk. The 2-year MD rate was 5.8%, with extent of resection, primary tumor type, and posterior fossa location being associated with MD risk. The 2-year any-grade ARE rate was 7.4%, with target margin expansion greater than 1 mm and melanoma primary being associated with ARE risk. Median OS was 17.2 months (95% CI, 14.1-21.3 months), with systemic disease status, extent of resection, and primary tumor type being the strongest prognostic factors associated with OS. In this cohort study, the rates of cavity LR, ARE, and MD after preoperative SRS were found to be notably low. Several tumor and treatment factors were identified that are associated with risk of cavity LR, ARE, MD, and OS after treatment with preoperative SRS. A phase 3 randomized clinical trial of preoperative vs postoperative SRS (NRG BN012) has began enrolling (NCT05438212).

Automatic Assessment of Stereotactic Radiation Therapy Outcome in Brain Metastasis Using Longitudinal Segmentation on Serial MRI.

The standard clinical approach to assess the radiotherapy outcome in brain metastasis is through monitoring the changes in tumour size on longitudinal MRI. This assessment requires contouring the tumour on many volumetric images acquired before and at several follow-up scans after the treatment that is routinely done manually by oncologists with a substantial burden on the clinical workflow. In this work, we introduce a novel system for automatic assessment of stereotactic radiation therapy (SRT) outcome in brain metastasis using standard serial MRI. At the heart of the proposed system is a deep learning-based segmentation framework to delineate tumours longitudinally on serial MRI with high precision. Longitudinal changes in tumour size are then analyzed automatically to assess the local response and detect possible adverse radiation effects (ARE) after SRT. The system was trained and optimized using the data acquired from 96 patients (130 tumours) and evaluated on an independent test set of 20 patients (22 tumours; 95 MRI scans). The comparison between automatic therapy outcome evaluation and manual assessments by expert oncologists demonstrates a good agreement with an accuracy, sensitivity, and specificity of 91%, 89%, and 92%, respectively, in detecting local control/failure and 91%, 100%, and 89% in detecting ARE on the independent test set. This study is a step forward towards automatic monitoring and evaluation of radiotherapy outcome in brain tumours that can streamline the radio-oncology workflow substantially.

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.

Stereotactic Radiosurgery for Meningiomas in Children and Adolescents: An International Multi-Institutional Study.

Meningiomas in children are uncommon, with distinct characteristics that set them apart from their adult counterparts. The existing evidence for stereotactic radiosurgery (SRS) in this patient population is limited to only case series. The objective of this study was to evaluate the safety and efficacy of SRS in managing pediatric meningiomas. Children and adolescents who had been treated for meningioma with single-fraction SRS were included in this retrospective, multicenter study. The assessment included local tumor control, any complications related to the tumor or SRS, and the emergence of new neurological deficits after SRS. The cohort included 57 patients (male-to-female ratio 1.6:1) with a mean age of 14.4 years who were managed with single-fraction SRS for 78 meningiomas. The median radiological and clinical follow-up periods were 69 months (range, 6-268) and 71 months (range, 6-268), respectively. At the last follow-up, tumor control (tumor stability and regression) was achieved in 69 (85.9%) tumors. Post-SRS, new neurological deficits occurred in 2 (3.5%) patients. Adverse radiation effects occurred in 5 (8.8%) patients. A de novo aneurysm was observed in a patient 69 months after SRS. SRS seems to be a safe and effective up-front or adjuvant treatment option for surgically inaccessible, recurrent, or residual pediatric meningiomas.

527 Multicentric Evaluation of Stereotactic Radiosurgery for Koos Grade IV Vestibular Schwannoma in Young Patients

INTRODUCTION: Koos IV vestibular schwannoma (VS) are preferably treated by surgery. However, SRS can be an alternative for patients with contraindications or who refuse surgery. SRS for Koos IV patient younger than 45 years old has not been previously studied and could be associated with more complications. METHODS: This is a retrospective multicentric study, performed under the International Radiosurgery Research Foundation. Patients 45 years old, treated primarily for a Koos IV VS with single-session SRS, presenting with non life-threatening or incapacitating symptoms, with a follow-up ≥1 years were included. RESULTS: 176 patients with a median age of 36 years (IQR 9) and a median tumor volume of 9.3 cm3 (IQR 4.7) were included. Before SRS, serviceable hearing, facial nerve weakness (House-Brachman >1) and trigeminal neuropathy was present in 51.7%, 8.5%, and 34.1% respectively. The median prescription dose was 12Gy (IQR 0.5). At a median follow-up of 3.1 years (IQR 4.5), tumor stability and regression were 38.9% and 54.3%, respectively. The 5- and 10-year progression-free rate was 90.9% and 86.7%. Early tumor enlargement occurred in 10.9% of cases. The probability of serviceable hearing preservation at 5- and 10-years was 56.8% and 45.2%, respectively. The probability of improvement or preservation of facial nerve function was 95.7% at 5 and 10-years. Adverse radiation effects were noted in 19.9%, 6 of them where managed with surgical resection of the VS. New-onset hydrocephalus occurred in 4.0%. CONCLUSIONS: Single-session SRS in selected Koos IV VS can be an alternative to surgery in a selected group of patients 45 years old. Long-term follow-up is warranted.

Gamma Knife radiosurgery for gynecologic metastases to the brain: Analysis of pathology, survival, and tumor control

ObjectiveThis study aims to evaluate the efficacy of stereotactic radiosurgery (SRS) in improving health outcomes of patients with gynecologic brain metastases. MethodsPatients with gynecologic metastases treated with SRS from 2008 to 2020 were retrospectively reviewed. The median age at SRS was 63 years old (cervical 45.5, endometrial 65.5, ovarian 61). The median number of tumors was 3 (range 1–27), and cumulative tumor volume was 2.33 cc (range 0.03–45.63). Median margin dose prescribed was 16 Gy (range 14 Gy – 20 Gy). The median 12 Gy volume was 7.30 cc (range 0.21–74.14 cc). Outcome variables included overall survival (OS) after SRS, local tumor control (LTC), distant tumor control, and adverse radiation effect (ARE). ResultsFifty patients (4 cervical, 25 endometrial, and 21 ovarian cancer) were identified. The OS at 6 and 12 months after SRS was 48%, and 44%, respectively. Eight patients (16%) died from CNS disease progression. The number of brain metastases (p = 0.011) and the Karnofsky Performance Scale (KPS) ≥ 70 (p = 0.020) were significant predictors of OS. LTC rate at 6 and 12 months were 92%, and 87%, respectively. Margin dose ≥16Gy correlated with significantly better local tumor control (p = 0.0001) without increased risk of ARE (p = 0.055). The risk of developing new metastases at 6 and 12 months were 12% and 24% respectively. SRS-induced ARE events occurred in 7 patients. ConclusionIntracranial metastases from gynecologic malignancy can be effectively treated using SRS with low risk of neurotoxicity. Margin dose ≥16Gy can provide significantly better tumor control. Repeat SRS can be utilized to treat new metastases while avoiding the potential cognitive symptoms associated with WBRT.

Adverse Radiation Effects Following Gamma Knife Radiosurgery.

Gamma Knife Radiosurgery (GKRS) is now an established standard of treatment for the small-sized arteriovenous malformations (AVMs), meningiomas, schwannomas, metastasis, and other benign diseases. With an exponential rise in the indications for GKRS, we have witnessed an increase in the adverse radiation effects (ARE) following GKRS. The common AREs and associated risk factors following GKRS have been described for pathologies including vestibular schwannomas, arteriovenous malformations, meningiomas, and metastases based on the authors' experience, and a simplified management protocol has been provided for radiation-induced changes based on clinical and radiologic parameters. The dose, volume, location, and repeat stereotactic radiosurgery (SRS) are implied as the risk factors for ARE. Clinically symptomatic AREs require oral steroids for weeks to alleviate symptoms. In refractory cases, bevacizumab and surgical resection can be offered as a treatment modality. Appropriate dose planning strategy and hypofractionation for larger lesions help in mitigating the AREs.

Gamma Knife Stereotactic Radiosurgery for Giant Intracranial Tumors - A Series of 70 Patients.

Surgery remains the primary option in large intracranial tumors, but significant number of patients may not be amenable for surgery. We explored the role of stereotactic radiosurgery as an alternative to external beam radiation therapy (EBRT) in such patients. Our study objective was to assess the clinicoradiological outcomes of large intracranial tumors (volume ≥20 cm3) managed with gamma knife radiosurgery (GKRS). This was a single-center, retrospective study conducted from January 2012 to December 2019. Patients with intracranial tumor volume ≥20 cm3 who received GKRS and had a minimum of 12 months of follow-up were included. Clinical, radiological, and radiosurgical details and clinicoradiological outcomes of the patients were obtained and analyzed. Seventy patients who had a pre-GKRS tumor volume ≥20 cm3 with >12 months of follow-up were included. The mean age of the patients was 41.9 ± 13.6 (range 11-75) years. Majority (97.1%) received GKRS in a single fraction. Mean pretreatment target volume was 31.9 ± 15.1 cm3. At a mean follow-up of 34.2 ± 17.1 months, tumor control was achieved in 91.4% (n = 64) of the patients. Adverse radiation effects were observed in 11 (15.7%) patients, but were symptomatic in only one (1.4%) patient. The present series defines "large intracranial lesions" for GKRS and demonstrates excellent radiological and clinical outcomes in these patients. GKRS may be considered as the primary option in such large intracranial lesions in which surgery carries significant risk based on patient-related factors.

SRS for Cavernous Malformations: Myths and Realities.

The optimal management of cavernous malformations (CMs) remains controversial. Over the past decade, stereotactic radiosurgery (SRS) has gained wider acceptance in the management of CMs, especially in those with deep location, eloquence, and where surgery is of high risk. Unlike arteriovenous malformations (AVMs), there is no imaging surrogate endpoint to confirm CM obliteration. Clinical response to SRS can only be gauged by a reduction in long-term CM hemorrhage rates. There is concern that the long-term benefits of SRS and the reduced rehemorrhage rate after a latency period of 2 years may only be a reflection of natural history. Of further concern is the development of adverse radiation effects (AREs), which were significant in the early experimental studies. The lessons learnt from that era have led to the progressive development of well-defined, lower marginal dose treatment protocols that have reported less toxicity (5%-7%) and consequently reduced morbidity. Currently, there is at least Class II, Level B evidence for use of SRS in solitary CMs with previous symptomatic hemorrhage in eloquent areas with high surgical risk. Recent prospective cohort studies observing untreated brainstem and thalamic CMs report significantly higher hemorrhage rates and neurological sequelae than the rates reported from contemporary pooled large natural history meta-analyses. Furthermore, this strengthens our recommendation for early proactive SRS in symptomatic deep-seated CMs due to the higher morbidity associated with observation and microsurgery. The key to successful outcomes for any surgical intervention is patient selection. We hope that our precis on contemporary SRS techniques in the management of CMs will assist this process.

SRS for Vestibular Schwannomas - Current Status.

Stereotactic radiosurgery (SRS) is an established modality of treatment for vestibular schwannomas (VS). We aim to summarize the evidence-based use of SRS in VSs and address the specific considerations pertaining to the same, along with our own clinical experiences. A thorough review of the literature was done to gather evidence regarding the safety and efficacy of SRS in VSs. Additionally, we have reviewed the senior author's experience in treating VSs (N = 294) between 2009 and 2021 and our experiences with microsurgery in post-SRS patients. Available scientific evidence upholds the role of SRS in VSs, in small-to-medium-sized tumors (5-year local tumor control >95%). The risk of adverse radiation effects remains minimal, while the hearing preservation rates are variable. Our center's post-GammaKnife VS follow-up cohort (sporadic - 157, neurofibromatosis-2 - 14) showed excellent tumor control rates at the last follow-up of 95.5% (sporadic) and 93.8% (neurofibromatosis-2), with a median margin dose of 13 Gy and mean follow-up periods of 3.6 (sporadic) and 5.2 (neurofibromatosis-2) years. Microsurgery in post-SRS VSs poses a formidable challenge due to the resulting thickened arachnoid and adhesions to critical neurovascular structures. Near-total excision is the key to better functional outcomes in such cases. SRS is here to stay as a trusted alternative in the management of VSs. Further studies are required to propose means of accurate prediction of hearing preservation rates and also to compare the relative efficacies of various SRS modalities.

Treatment of adverse radiation effects with Boswellia serrata after failure of pentoxifylline and vitamin E: illustrative cases.

Adverse radiation effects (AREs) can occur after stereotactic radiosurgery (SRS), and symptomatic cases are often treated with corticosteroids, pentoxifylline, and vitamin E. The supplement 5-Loxin (Boswellia serrata) is an extract of Indian frankincense that inhibits vascular endothelial growth factor expression and has been shown to reduce perilesional edema in brain tumor patients undergoing fractionated radiation. Three patients underwent SRS for meningioma or metastasis and developed symptomatic AREs at 4 to 8 months. They were initially treated with corticosteroids, pentoxifylline, and vitamin E with transient improvement followed by recurrent neurological symptoms and imaging findings as steroids were tapered off. All patients were rescued by the administration of 5-Loxin with resolution of neurological symptoms and imaging changes, discontinuation of steroids, and no medication side effects. The author's early experience with 5-Loxin has been encouraging, and this supplement has become the author's first-line treatment for acute radiation effects after SRS. The author reserves bevacizumab for significant mass effect or failure of oral therapy. 5-Loxin has many advantages including low cost, ease of use, and patient tolerability. More experience is needed to confirm the role of 5-Loxin in the upfront treatment of AREs.

Adverse radiation effect and freedom from progression following repeat stereotactic radiosurgery for brain metastases.

The authors previously evaluated risk and time course of adverse radiation effects (AREs) following stereotactic radiosurgery (SRS) for brain metastases, excluding lesions treated after prior SRS. In the present analysis they focus specifically on single-fraction salvage SRS to brain metastases previously treated with SRS or hypofractionated SRS (HFSRS), evaluating freedom from progression (FFP) and the risk and time course of AREs. Brain metastases treated from September 1998 to May 2019 with single-fraction SRS after prior SRS or HFSRS were analyzed. Serial follow-up magnetic resonance imaging (MRI) and surgical pathology reports were reviewed to score local treatment failure and AREs. The Kaplan-Meier method was used to estimate FFP and risk of ARE measured from the date of repeat SRS with censoring at the last brain MRI. A total of 229 retreated brain metastases in 124 patients were evaluable. The most common primary cancers were breast, lung, and melanoma. The median interval from prior SRS/HFSRS to repeat SRS was 15.4 months, the median prescription dose was 18 Gy, and the median duration of follow-up imaging was 14.5 months. At 1 year after repeat SRS, FFP was 80% and the risk of symptomatic ARE was 11%. The 1-year risk of imaging changes, including asymptomatic RE and symptomatic ARE, was 30%. Among lesions that demonstrated RE, the median time to onset was 6.7 months (IQR 4.7-9.9 months) and the median time to peak imaging changes was 10.1 months (IQR 5.6-13.6 months). Lesion size by quadratic mean diameter (QMD) showed similar results for QMDs ranging from 0.75 to 2.0 cm (1-year FFP 82%, 1-year risk of symptomatic ARE 11%). For QMD < 0.75 cm, the 1-year FFP was 86% and the 1-year risk of symptomatic ARE was only 2%. Outcomes were worse for QMDs 2.01-3.0 cm (1-year FFP 65%, 1-year risk of symptomatic ARE 24%). The risk of symptomatic ARE was not increased with tyrosine kinase inhibitors or immunotherapy before or after repeat SRS. RE on imaging was common after repeat SRS (30% at 1 year), but the risk of a symptomatic ARE was much less (11% at 1 year). The results of repeat single-fraction SRS were good for brain metastases ≤ 2 cm. The authors recommend an interval ≥ 6 months from prior SRS and a prescription dose ≥ 18 Gy. Alternatives such as HFSRS, laser interstitial thermal therapy, or resection with adjuvant radiation should be considered for recurrent brain metastases > 2 cm.