Gamma knife radiosurgery for clival metastasis: case series and systematic review.

PURPOSE: Clival metastatic cancer is rare and has limited literature to guide management. We describe management of clival metastasis with Gamma Knife radiosurgery (GKRS). We augment our findings with a systematic review of all forms of radiation therapy for clival metastasis. METHODS: Records of 14 patients with clival metastasis who underwent GKRS at the University of Pittsburgh Medical Center from 2002 to 2023 were reviewed. Treatment parameters and clinical outcomes were assessed. A systematic review was conducted using evidence-based guidelines. RESULTS: The average age was 61 years with male predominance (n = 10) and average follow-up of 12.4 months. The most common primary cancers were prostate (n = 3) and lung (n = 3). The average time from cancer diagnosis to clival metastasis was 34 months. The most common presenting symptoms were headache (n = 9) and diplopia (n = 7). Five patients presented with abducens nerve palsies, and two presented with oculomotor nerve palsies. The median tumor volume was 9.3 cc, and the median margin dose was 15 Gy. Eleven patients achieved tumor control after one procedure, and three with progression obtained tumor control after repeat GKRS. One patient recovered abducens nerve function. The median survival from cancer diagnosis and GKRS were 49.7 and 15.3 months, respectively. The cause of death was progression of systemic cancer in six patients, clival metastasis in one, and unknown in four. The systematic review included 31 studies with heterogeneous descriptions of treatment and outcomes. CONCLUSION: Clival metastasis is rare and associated with poor prognosis. GKRS is a safe, effective treatment for clival metastasis.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

BACKGROUND: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

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

OBJECTIVE: This study aims to evaluate the efficacy of stereotactic radiosurgery (SRS) in improving health outcomes of patients with gynecologic brain metastases. METHODS: Patients 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). RESULTS: Fifty 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. CONCLUSION: Intracranial 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.

Gamma Knife radiosurgery for meningiomas of the confluence of the falx and tentorium.

PURPOSE: Meningiomas arising from the confluence of the falx and tentorium (CFT) are a rare and challenging subset of meningiomas. Gamma Knife radiosurgery (GKRS) is well-established as a safe and effective management strategy for intracranial meningiomas, but its role in treating CFT meningiomas is not well-described. This paper reports the largest series focused exclusively on the outcomes of GKRS for CFT meningiomas. METHODS: We retrospectively identified 20 CFT meningiomas out of 2031 meningioma patients who underwent GKRS at our institution between 1987 and 2021. Tumor control, overall survival (OS), and complications were recorded and analyzed. The median tumor margin dose was 13 Gy at the 50% isodose line. The median tumor volume treated was 4.4 cc (IQR 3.5-7.7). The median patient age was 58 years (range 33-83), the median MRI surveillance duration was 59 months (IQR 34-92), and the median overall follow-up duration was 92 months (IQR 42-201). RESULTS: The local tumor control rate (PFS) at 5 and 10-years were 100% (N=10) and 83% (N=4), respectively. Eight patients had stable tumor volumes and 11 patients had regression. One patient with a twice-operated tumor had delayed progression at 7.5 years and was retreated with GKRS. No patient had adverse radiation effects during the period of MRI surveillance. The 5 and 10-year OS were 100% (N=13) and 100% (N=7), respectively. CONCLUSIONS: GKRS is a valuable therapeutic strategy for patients with newly diagnosed CFT meningiomas or progressive residual tumors after surgical resection.

Stereotactic radiosurgery for patients with brain metastases from gastroesophageal cancers.

BACKGROUND: 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). METHODS: 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 6.7 cc (range: 0.27-104.76) and the median single-session margin dose was 18 Gy (range: 12-20). RESULTS: 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%. CONCLUSIONS: 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.

Phase II study of border zone stereotactic radiosurgery with bevacizumab in patients with recurrent or progressive glioblastoma multiforme.

PURPOSE: Recurrent glioblastoma is universally fatal with limited effective treatment options. The aim of this phase 2 study of Border Zone SRS plus bevacizumab was to evaluate OS in patients with recurrent GBM. METHODS: Patients with histologically confirmed GBM with recurrent disease who had received prior first-line treatment with fractionated radiotherapy and chemotherapy and eligible for SRS were enrolled. Bevacizumab 10 mg/kg was given day -1, day 14, and then every 14 days until disease progression. 1-14 days before BZ-SRS procedure, patients underwent brain MRI /MRS. MRS with measurement of choline-to-N-acetyl aspartate index (CNI) area ≥ 3 was targeted for SRS. RESULTS: From 2015-2017, sixteen of planned 40 patients were enrolled. The median age was 62 (range, 48-74Y). 3/16 (0.188) participants experienced grade 2 toxicity. No AREs were reported. The mOS was 11.73 months compared to 8.74 months (P = 0.324) from date of SRS for the BZ-SRS and institutional historical controls, respectively. PFS-6 and OS-6 were 31.2% (p = 0.00294) and 81.2%(p = 0.058), respectively. Of 13 evaluable for best response: 1 CR (p = 0.077), 4 PR (p = 0.308), 7 SD (p = 0.538), and 1 PD (p = 0.077). 11/16 participants had MRS scans with an estimated probability that MRS changes a treatment plan of 0 (0, 0.285). CONCLUSION: BZ-SRS with bevacizumab was feasible and well tolerated. There is no significant survival benefit using BZ-SRS with bevacizumab compared to institutional historical controls. Secondary analysis revealed a trend toward improved PFS-6, but not OS-6 after BZ-SRS. MRS scans did not result in changes to SRS treatment plans.

Radiosurgery outcomes in infratentorial juvenile pilocytic astrocytomas.

PURPOSE: To assess survival and neurological outcomes for patients who underwent primary or salvage stereotactic radiosurgery (SRS) for infratentorial juvenile pilocytic astrocytomas (JPA). METHODS: Between 1987 and 2022, 44 patients underwent SRS for infratentorial JPA. Twelve patients underwent primary SRS and 32 patients underwent salvage SRS. The median patient age at SRS was 11.6 years (range, 2-84 years). Prior to SRS, 32 patients had symptomatic neurological deficits, with ataxia as the most common symptom in 16 patients. The median tumor volume was 3.22 cc (range, 0.16-26.6 cc) and the median margin dose was 14 Gy (range, 9.6-20 Gy). RESULTS: The median follow-up was 10.9 years (range, 0.42-26.58 years). Overall survival (OS) after SRS was 97.7% at 1-year, and 92.5% at 5- and 10-years. Progression free survival (PFS) after SRS was 95.4% at 1-year, 79.0% at 5-years, and 61.4% at 10-years. There is not a significant difference in PFS between primary and salvage SRS patients (p = 0.79). Younger age correlated with improved PFS (HR 0.28, 95% CI 0.063-1.29, p = 0.021). Sixteen patients (50%) had symptomatic improvements while 4 patients (15.6%) had delayed onset of new symptoms related to tumor progression (n = 2) or treatment related complications (n = 2). Tumor volumetric regression or disappearance after radiosurgery was found in 24 patients (54.4%). Twelve patients (27.3%) had delayed tumor progression after SRS. Additional management of tumor progression included repeat surgery, repeat SRS, and chemotherapy. CONCLUSIONS: SRS was a valuable alternative to initial or repeat resection for deep seated infratentorial JPA patients. We found no survival differences between patients who had primary and salvage SRS.

Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients.

PURPOSE: Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently. METHODS: A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN). RESULTS: The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2 months. The median age was 67 years. The median margin SRS dose was 19 Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95). CONCLUSION: The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.

Does Adjuvant Gamma Knife Stereotactic Radiosurgery Have a Role in Treating Optic Nerve Sheath Meningiomas?

BACKGROUND: Meningiomas arising from or adjacent to the optic nerve sheath meningioma (ONSM) are management challenges because of their risk of visual loss. Stereotactic radiosurgery (SRS) is a minimally invasive modality that can be added as adjuvant treatment for patients whose tumor has progressed or recurred after initial resection. METHODS: The authors retrospectively reviewed 2,030 meningioma patients who underwent SRS between 1987 and 2022. In total, 7 patients (4 females; median age = 49) were found with tumors originating from the optic nerve sheath. None of the patients had tumors that engulfed the optic nerve as such tumors typically undergo fractionated radiation therapy (FRT) to preserve vision. The clinical history, visual function, and radiographic and neurological findings were characterized. Outcome measures included visual status, tumor control, and the need for additional management. RESULTS: All patients underwent either initial gross total (n = 1) or partial surgical resection (n = 6) before SRS. Two patients with progressive tumor growth also had SRS after failing additional fractionated radiation after surgery (54 Gy, 30 fractions for both patients). The median time between the date of surgery and the SRS procedure date was 38 months. The Leksell Gamma Knife was used to deliver a margin dose of 12 Gy (range: 8-14 Gy) to a median cumulative tumor volume of 3.3 cc (range: 1.2-18 cc). The median maximal optic nerve radiation dose was 6.5 Gy (range: 1.9-8.1 Gy). After SRS, the median follow-up time was 130 months (range: 26-169 months). Two patients showed local tumor progression at 20 and 55 months after SRS. Four had stable visual function, 2 experienced improved visual acuity, and 1 patient had visual deterioration. CONCLUSIONS: Meningiomas arising from (but not engulfing the optic nerve) represent management quandaries after failed initial surgical removal. In this experience, salvage SRS was associated with tumor control and vision preservation in 5 of 7 patients. Additional experience with this strategy may further define the role of SRS both as a salvage and primary option.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in patients ≥ 65 years old: a multi-institutional retrospective study.

BACKGROUND: Surgery is the preferred treatment for large vestibular schwannomas (VS). Good tumor control and cranial nerve outcomes were described in selected Koos IV VS after single-session stereotactic radiosurgery (SRS), but outcomes in elderly patients have never been specifically studied. The aim of this study is to report clinical and radiological outcomes after single-session SRS for Koos IV VS in patients ≥ 65 years old. METHOD: This multicenter, retrospective study included patients ≥ 65 years old, treated with primary, single-session SRS for a Koos IV VS, and at least 12 months of follow-up. Patients with life-threatening or incapacitating symptoms were excluded. Tumor control rate, hearing, trigeminal, and facial nerve function were studied at last follow-up. RESULTS: One-hundred and fifty patients (median age of 71.0 (IQR 9.0) years old with a median tumor volume of 8.3 cc (IQR 4.4)) were included. The median prescription dose was 12.0 Gy (IQR 1.4). The local tumor control rate was 96.0% and 86.2% at 5 and 10 years, respectively. Early tumor expansion occurred in 6.7% and was symptomatic in 40% of cases. A serviceable hearing was present in 16.1% prior to SRS and in 7.4% at a last follow-up of 46.5 months (IQR 55.8). The actuarial serviceable hearing preservation rate was 69.3% and 50.9% at 5 and 10 years, respectively. Facial nerve function preservation or improvement rates at 5 and 10 years were 98.7% and 91.0%, respectively. At last follow-up, the trigeminal nerve function was improved in 14.0%, stable in 80.7%, and worsened in 5.3% of the patients. ARE were noted in 12.7%. New hydrocephalus was seen in 8.0% of patients. CONCLUSION: SRS can be a safe alternative to surgery for selected Koos IV VS in patients ≥ 65 years old. Further follow-up is warranted.

Management of sarcomatoid Malignant pleural mesothelioma brain metastases with stereotactic radiosurgery: an Illustrative case.

Background: Malignant pleural mesothelioma (MPM) is a rare cancer of the respiratory system that rarely metastasizes to the brain. We report a case of sarcomatoid MPM (SMPM) managed with Stereotactic radiosurgery (SRS) to achieve intracranial tumor control and improve neurological symptoms.Illustrative case: This 67-year-old female patient underwent SRS twice in order to treat a total of 15 brain metastases. One-month follow-up imaging after the first SRS demonstrated local tumor response and seven tumors with symptomatic vasogenic edema that responded to initial corticosteroids followed by bevacizumab. At a three-month follow-up after the first procedure, eight new tumors were detected and required repeat SRS. Although sustained tumor control resulted in improved neurological function, the patient subsequently expired from systemic disease progression 12 months after initial diagnosis and six months after initial SRS for brain metastases despite the concurrent use of systemic immunotherapy and systemic chemotherapy.Conclusions: Although SRS provided overall tumor control of metastatic brain disease, further advances in systemic therapies will be needed to improve survival in this aggressive rare cancer.

Intracerebral and pituitary metastatic eccrine carcinoma: prolonged survival using stereotactic radiosurgery.

PURPOSE: Eccrine gland carcinoma (EC) is a rare skin neoplasm that uncommonly spreads to the brain or pituitary gland. We describe the role of multiple stereotactic radiosurgery (SRS) procedures to manage recurrent brain metastases of this rare disease. MATERIALS AND METHODS: Retrospective chart review was completed to obtain details for this report. The study was performed under IRB study on medical record only and was exempt from patient's consent. RESULTS AND CONCLUSIONS: A 59-year-old female underwent surgical excision of a right parietal scalp EC. Over the next 13 years, the patient underwent initial fractionated whole brain radiation therapy after she developed multiple brain metastases followed by systemic chemotherapy for extracranial disease. Because of repeated development of new brain disease, three SRS procedures were performed to treat a total of 50 brain metastases and a pituitary metastasis (PM). The patient expired from progressive systemic cancer spread 13 years after her initial surgical excision. Due to the rarity of metastatic EC to the brain, no standard treatment paradigm has emerged. Using multimodality options that included local excision of the original skin tumor, followed by radiation, systemic chemotherapy, and three SRS procedures, long-term survival was possible in this unusual case.

Radiation necrosis in renal cell carcinoma brain metastases treated with checkpoint inhibitors and radiosurgery: An international multicenter study.

BACKGROUND: Patients with renal cell carcinoma (RCC) brain metastases are frequently treated with immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS). However, data reporting on the risk of developing radiation necrosis (RN) are limited. METHODS: RN rates were compared for concurrent therapy (ICI/SRS administration within 4 weeks of one another) and nonconcurrent therapy with the χ2 test. Univariable logistic regression was used to identify factors associated with developing RN. RESULTS: Fifty patients (23 concurrent and 27 nonconcurrent) with 395 brain metastases were analyzed. The median follow-up was 12.1 months; the median age was 65 years. The median margin dose was 20 Gy, and 4% underwent prior whole-brain radiation therapy (WBRT). The median treated tumor volume was 3.32 cm3 (range, 0.06-42.38 cm3 ); the median volume of normal brain tissue receiving a dose of 12 Gy or higher (V12 Gy) was 8.42 cm3 (range, 0.27-111.22 cm3 ). Any-grade RN occurred in 17.4% and 22.2% in the concurrent and nonconcurrent groups, respectively (P = .67). Symptomatic RN occurred in 4.3% and 14.8% in the concurrent and nonconcurrent groups, respectively (P = .23). Increased tumor volume during SRS (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.19; P = .04) was associated with developing RN, although V12 Gy (OR, 1.03; 95% CI, 0.99-1.06; P = .06), concurrent therapy (OR, 0.74; 95% CI, 0.17-2.30; P = .76), prior WBRT, and ICI agents were not statistically significant. CONCLUSIONS: Symptomatic RN occurs in a minority of patients with RCC brain metastases treated with ICI/SRS. The majority of events were grade 1 to 3 and were managed medically. Concurrent ICI/SRS does not appear to increase this risk. Attempts to improve dose conformality (reduce V12) may be the most successful mitigation strategy in single-fraction SRS.

Outcomes after gamma knife radiosurgery for intraventricular meningiomas.

BACKGROUND: Intraventricular meningiomas (IVMs) are rare tumors with considerable treatment-associated morbidity due to their challenging location. Treatment with stereotactic radiosurgery (SRS) is sparsely reported in the literature. We describe our experience over the last 35 years using Gamma knife radiosurgery (GKRS) for IVMs. METHODS: We retrospectively reviewed the GKRS database identifying 2501 meningiomas treated at the University of Pittsburgh Medical Center over the last 35 years. Nineteen patients with (12 males, mean age = 53.2 years, range 14-84) 20 IVMs were identified. Headache was the most frequent presenting symptom (N = 12), and the trigone of the lateral ventricle was the most common location (N = 18). The median tumor volume was 4.8 cc (range, 0.8-17). The median margin dose was 14 Gy (range, 12-25) delivered at 50% isodose line. RESULTS: At a median follow-up of 63.1 months (range, 6-322.4) symptom control was achieved in 18 (94.7%) patients. The overall progression-free survival (PFS) was 95% at 5 years, and 85% at 10-years. After Log-rank test, patients who underwent GKRS within 12 months after diagnosis (vs. ≥ 12 months, X2: 4.455, p = 0.035), patients treated with primary GKRS without prior biopsy (vs. prior biopsy, X2: 4.000, p = 0.046), and patients with WHO grade I meningioma (vs. WHO II, X2: 9.000, p = 0.003) had a longer PFS. Imaging showed peritumoral edema in seven cases at a median of 10.5 (range, 6.13-24.3) months after GKRS. Only three of these patients were symptomatic and were successfully managed with oral medications. Cox´s regression revealed that a V12Gy ≥ 10 cc [HR: 10.09 (95% CI: 2.11-48.21), p = 0.004], and tumor volume ≥ 8 cc [HR: 5.87 (95% CI: 1.28-26.97), p = 0.023] were associated with a higher risk of peritumoral edema. CONCLUSION: GKRS is an effective and safe management option for intraventricular meningiomas. Early GKRS should be considered as a primary management modality for small and medium sized IVM and adjuvant management for residual IVMs.

A volume matched comparison of survival after radiosurgery in non-small cell lung cancer patients with one versus more than twenty brain metastases.

BACKGROUND: Treatment of patients with a large number of brain metastases using radiosurgery remains controversial. In this study we sought to conduct a volume matched comparison to evaluate the clinical outcome of patients with > 20 brain metastases and compared it with patents with solitary brain tumor form non-small cell lung cancer (NSCLC). METHODS: Between 2014 and 2020, 26 NSCLC patients (925 tumors) underwent stereotactic radiosurgery (SRS) for > 20 metastases in a single procedure (median margin dose = 16 Gy, median cumulative tumor volume = 4.52 cc); 56 patients underwent SRS for a single metastasis (median margin dose = 18 Gy, median volume = 4.74 cc). The overall survival (OS), local tumor control (LC), adverse radiation effect (ARE) risk, and incidence of new tumor development were compared. RESULTS: No difference in OS was found between patients with > 20 brain metastases (median OS = 15 months) and patients with solitary metastasis (median OS = 12 months; p = 0.3). In the solitary tumor cohort, two of 56 (3.5%) tumors progressed whereas in the > 20 cohort only 3 of 925 (0.3%) tumors showed progression (*p = 0.0013). The rate of new tumor development was significantly higher in patients with > 20 tumors (***p = 0.0001). No significant difference of ARE rate was found (7.5% for > 20 tumors vs. 8.7% for single metastasis). CONCLUSIONS: Patients with > 20 tumors showed significantly better LC with similar OS compared to patients with solitary tumors. Current guidelines that restrict the role of SRS to patients with 1-4 tumors should be revised.

Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in young patients: a multi-institutional study.

PURPOSE: Surgery is the treatment of choice for large vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has been suggested as an alternative to resection in selected patients. However, the safety and efficacy of SRS in Koos grade IV patients ≤ 45 years old has not been evaluated. The aim of this study is to describe the clinical and radiological outcomes of Koos grade IV in young patient managed with a single-session SRS. METHODS: This retrospective, multicenter analysis included SRS-treated patients, ≤ 45 years old presenting with non-life threatening or incapacitating symptoms due to a Koos Grade IV VS and with follow-up ≥ 12 months. Tumor control and neurological outcomes were evaluated. RESULTS: 176 patients [median age of 36.0 (IQR 9) and median tumor volume of 9.3 cm3 (IQR 4.7)] were included. The median prescription dose was 12 Gy (IQR 0.5). Median follow-up period was 37.5 (IQR 53.5) months. The 5- and 10-year progression-free survival was 90.9% and 86.7%. Early tumor enlargement occurred in 10.9% of cases and was associated with tumor progression at the last follow-up. 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%. New-onset hydrocephalus occurred in 4.0%. CONCLUSION: Single-session SRS is a safe and effective alternative to surgical resection in selected patients ≤ 45 years old particularly those with medical co-morbidities and those who decline resection. Longer term follow up is warranted.

The role of stereotactic radiosurgery in the multidisciplinary management of pituitary metastases.

PURPOSE: This study evaluates the role and outcomes of Gamma Knife radiosurgery (GKRS) in the management of pituitary metastases. METHODS: The records of brain metastases patients who underwent GKRS at the University of Pittsburgh Medical Center during the 10-year interval of 2010-2020 were systematically reviewed. Outcome measures included patient survival, tumor control rate, pituitary hormonal outcomes, visual outcomes, adverse radiation effects (AREs), and need for adjuvant therapy. RESULTS: Eighteen patients with pituitary metastases (eight male; median age of 65.5 years) had sufficient clinical follow-up for analysis. The most common primary cancers were non-small cell lung cancer (n = 6) and breast cancer (n = 4). Patients presented with headache (n = 9) and visual difficulties (n = 6). One patient underwent resection before GKRS. The median tumor volume was 0.78 cc (range 0.04-6.42 cc). The median overall survival after GKRS was 6.5 months (range 0.5-58 months). The overall survival after GKRS at 3-, 6-, and 12-months were 72.2%, 50.0% and 38.9%, respectively. The tumor control rate was 94.4%. One patient had further progression that required additional GKRS. None of the patients developed AREs after GKRS. CONCLUSION: GKRS is an effective treatment modality for the multidisciplinary management of patients with pituitary metastases. This minimally-invasive strategy is associated with optimal tumor control rate and low risk to adjacent optic nerves or neurovascular structures.

Stereotactic radiosurgery for the treatment of hypoglossal schwannoma: a multi-institutional retrospective study.

BACKGROUND: Surgical removal has been performed as the first line treatment for symptomatic or enlarging hypoglossal schwannomas (HS). Stereotactic radiosurgery (SRS) offers a minimally invasive approach that may afford long-term tumor control for patients with HS particularly those who refuse or are unfit for surgery. This study evaluates outcomes after SRS performed for both newly diagnosed and residual tumors after incomplete resection. METHODS: This retrospective, multi-institutional study involved patients treated with adjuvant or primary SRS for HS. The study end-points included local tumor response, clinical outcomes, and procedure-related complications. All the patients had Gamma Knife SRS. RESULTS: The cohort included 12 patients (five females), median age at SRS 49.5 years (range, 37-76)]. The median tumor target volume was 5.9 cm3 (range, 0.7-27.23). At median imaging follow-up of 37 months (range, 6-153), tumor control was achieved in 11 patients. Tumor enlargement that was managed with surgical resection was noted at the 6-month follow-up in one patient. At median clinical follow-up of 30.5 months (range, 6-157), stability, or improvement of all pre-SRS signs and symptoms was noted in nine patients. Two patients experienced worsening of at least one pre-existing symptoms or sign. New-onset trapezius weakness was noted in one patient and tongue atrophy in two patients. CONCLUSION: Single-fraction SRS appears to be a safe and effective upfront and adjuvant treatment option for HS. SRS may be recommended as an alternative to surgery for patients presenting with HS or as an adjuvant treatment following subtotal resection and at HS recurrence.

Optimizing stereotactic radiosurgery in patients with recurrent or residual craniopharyngiomas.

PURPOSE: Stereotactic radiosurgery (SRS) is an important management strategy for residual and recurrent craniopharyngiomas. The current study evaluated the factors which affected tumor control and complications in craniopharyngioma SRS. METHODS: This study includes 53 consecutive patients who underwent single-session SRS for recurrent or residual craniopharyngiomas. The median age was 41 years with 28 male and 25 females. The median tumor volume was 0.63 cm3 and median margin dose was 12 Gy (range 9-25 Gy). RESULTS: The overall 3-, 5-, and 10-year survival rates were 97.8%, 92.7% and 88.5%. The overall 3-, 5-, and 10-year tumor control rates were 81.0%, 72.1%, and 53.4%. In univariate analysis, ≥ 3 mm distance from optic structures (p = 0.002), only solid or cystic tumor type (p = 0.037), and ≥ 12 Gy to ≥ 85% of the tumor (p < 0.001) were significantly associated with improved tumor control. In multivariate analysis, only solid or cystic tumor type, (p = 0.034), and ≥ 85% of the tumor receiving ≥ 12 Gy (p = 0.004) were significantly associated with better tumor control. When ≥ 85% of the tumor received ≥ 12 Gy the tumor control rates at 3-, 5-, and 10-year were 100%, 93.3%, and 93.3%. Higher conformity index was not associated with better tumor control. CONCLUSIONS: The tumor control rates after recurrent or residual craniopharyngiomas SRS were improved by ensuring that at least 85% of the tumor received ≥ 12 Gy even when the distance between the tumor and the optic system is < 3 mm. This concept refutes the conformity theory that a high conformity index is a critical feature of effective SRS.

Useful hearing preservation is improved in vestibular schwannoma patients who undergo stereotactic radiosurgery before further hearing deterioration ensues.

INTRODUCTION: The present study evaluates whether hearing deterioration during observation reduces serviceable hearing preservation rates after stereotactic radiosurgery (SRS) in vestibular schwannoma (VS) patients with useful hearing. METHODS: We retrospectively analyzed 1447 VS patients who underwent SRS between 1992 and 2017. We identified 100 VS patients who had Grade I Gardner- Robertson (GR) hearing at initial diagnosis but were observed without surgery or SRS. We compared hearing after SRS in 67 patients who retained GR Grade I hearing from initial diagnosis to SRS (the hearing maintenance or HM group) to 33 patients whose hearing worsened from GR grade I to grade II (the hearing deterioration or HD group). We also investigated whether a decline in pure tone average (PTA) or speech discrimination score (SDS) before SRS affected hearing preservation after SRS. RESULTS: The serviceable hearing (GR I and II) preservation in HM patients was 80%s, 63%, and 51% at 3, 5, and 10 years, respectively. The serviceable hearing preservation in HD patients was 40%, 33%, and 20% at 3, 5, and 10 years, respectively. In multivariate analysis, younger age (< 55 years, p = 0.045) and HM during observation (p = 0.001) improved serviceable hearing preservation rates. Patients whose PTA increased ≥ 15 dB (p = 0.024) or whose SDS declined ≥ 10% (p = 0.019) had reduced serviceable hearing preservation rates. CONCLUSIONS: Hearing deterioration during observation before SRS reduced long term hearing preservation rate in VS patients with GR grade I hearing at initial diagnosis. SRS before hearing deterioration was recommended for hearing preservation.