Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Clinical outcomes following stereotactic radiosurgery for cerebral cavernous malformations of the basal ganglia and thalamus.

OBJECTIVE: There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes. METHODS: Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs. RESULTS: Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4-79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07-10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10-20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006). CONCLUSIONS: SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.

Adjuvant Stereotactic Radiosurgery With or Without Postresection Fractionated Radiation Therapy for the Management of Clival Chordomas in Adults: An International Multicenter Case Series.

BACKGROUND: Clival chordomas are challenging because of their proximity to critical neurovascular structures. Stereotactic radiosurgery (SRS) has been proven effective with minimal adverse effects. OBJECTIVE: To compare the outcomes of histologically confirmed primary clival chordomas in adults who underwent SRS alone (SRS group) vs SRS after fractionated radiotherapy (FRT+SRS group). METHODS: We collected patient data from 10 institutions affiliated with the International Radiosurgery Research Foundation. We evaluated overall survival, tumor control, and freedom from additional treatment (FFAT). RESULTS: Fifty-seven (77%) patients were included in the SRS group and 17 (23%) in the FRT+SRS group. The median radiological follow-up was 48 months (IQR, 24-85) in the SRS group and 36 months (IQR, 25-41) in the FRT+SRS group. During the follow-up, 8 SRS and 2 FRT+SRS patients died ( P = .80). The groups had comparable 10-year overall survival (SRS: 76% vs FRT+SRS: 80%; logrank test, P = .75) and tumor control rates (SRS: 34% vs FRT+SRS: 45%; logrank test, P = .29). The SRS group had a superior 10-year FFAT rate (40%) compared with FRT+SRS (23%; logrank test, P = .02). This finding persisted in the multivariate analysis of the Cox proportional hazards illustrating a 2.40-fold increase in the relative risk of requiring additional treatment among the FRT+SRS group ( P = .04). CONCLUSION: Adjuvant FRT with subsequent boost SRS did not provide superior overall survival or tumor control compared with patients who underwent adjuvant SRS alone. Further studies are required to refine management guidelines among adults with clival chordomas.

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.

Stereotactic Radiosurgery for Intraventricular Metastases: A Multicenter Study.

BACKGROUND: Intraventricular metastases (IVMs) are uncommon, and their optimal management remains debatable. OBJECTIVE: To define the safety and efficacy of stereotactic radiosurgery (SRS) in the treatment of IVMs. METHODS: This retrospective, multicenter study included patients managed with SRS for IVMs. SRS-induced adverse events, local tumor or intracranial progression, and the frequency of new-onset hydrocephalus or leptomeningeal spread were documented. Analyses of variables related to patient neuroimaging or clinical outcomes were also performed. RESULTS: The cohort included 160 patients from 11 centers who underwent SRS for treatment of 1045 intracranial metastases, of which 196 were IVMs. The median survival from SRS was 10 months. Of the 154 patients and 190 IVMs with imaging follow-up, 94 patients (61%) experienced distant intracranial disease progression and 16 IVMs (8.4%) progressed locally. The 12- and 24-month local IVM control rates were 91.4% and 86.1%, respectively. Sixteen (10%) and 27 (17.5%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Adverse radiation effects were documented in 24 patients (15%). Eleven patients (6.9%) died because of intracranial disease progression. CONCLUSION: SRS is an effective treatment option for IVMs, with a local IVM control rate comparable with SRS for parenchymal brain metastases. Leptomeningeal spread and hydrocephalus in patients with IVM occur in a minority of patients, but these patients warrant careful follow-up to detect these changes.

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

OBJECTIVE: Though stereotactic radiosurgery (SRS) is an established safe treatment for small- and medium-sized vestibular schwannomas (VSs), its role in the management of Koos grade IV VS is still unclear. In this retrospective multicenter study, the authors evaluated tumor control and the patient outcomes of primary, single-session SRS treatment for Koos grade IV VS. METHODS: This study included patients treated with primary, single-session SRS for Koos grade IV VS at 10 participating centers. Only those patients presenting with non-life-threatening or incapacitating symptoms and at least 12 months of clinical and neuroimaging follow-up were eligible for inclusion. Relevant data were collected, and the Kaplan-Meier method was used to perform time-dependent analysis for post-SRS tumor control, hearing preservation, and facial nerve function preservation. Univariate and multivariate analyses were performed for outcome measures using Cox regression analysis. RESULTS: Six hundred twenty-seven patients (344 females, median patient age 54 [IQR 22] years) treated with primary SRS were included in this study. The median tumor volume was 8.7 (IQR 5) cm3. Before SRS, serviceable hearing, facial nerve weakness (House-Brackmann grade > I), and trigeminal neuropathy were present in 205 (33%), 48 (7.7%), and 203 (32.4%) patients, respectively. The median prescription dose was 12 (IQR 1) Gy. At a median radiological follow-up of 38 (IQR 54) months, tumor control was achieved in 94.1% of patients. Early tumor expansion occurred in 67 (10.7%) patients and was associated with a loss of tumor control at the last follow-up (p = 0.001). Serviceable hearing preservation rates at the 5- and 10-year follow-ups were 65% and 44.6%, respectively. Gardner-Robertson class > 1 (p = 0.003) and cochlear dose ≥ 4 Gy (p = 0.02) were risk factors for hearing loss. Facial nerve function deterioration occurred in 19 (3.0%) patients at the last follow-up and was associated with margin doses ≥ 13 Gy (p = 0.03) and early tumor expansion (p = 0.04). Post-SRS, 33 patients developed hydrocephalus requiring shunting. Adverse radiation effects occurred in 92 patients and were managed medically or surgically in 34 and 18 cases, respectively. CONCLUSIONS: SRS is a safe and effective method of obtaining tumor control in patients with Koos grade IV VS presenting with non-life-threatening or debilitating symptoms, especially those with surgical comorbidities that contraindicate resection. To decrease the incidence of post-SRS facial palsy, a prescription dose < 13 Gy is recommended.

Adjuvant versus on-progression Gamma Knife radiosurgery for residual nonfunctioning pituitary adenomas: a matched-cohort analysis.

OBJECTIVE: Radiological progression occurs in 50%-60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs. METHODS: This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed. RESULTS: Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55-4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6-12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = -0.8%, p > 0.99) or visual deficits (RD = -2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01). CONCLUSIONS: SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

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.

Stereotactic radiosurgery for intracranial chordomas: an international multiinstitutional study.

OBJECTIVE: The object of this study was to evaluate the safety, efficacy, and long-term outcomes of stereotactic radiosurgery (SRS) in the management of intracranial chordomas. METHODS: This retrospective multicenter study involved consecutive patients managed with single-session SRS for an intracranial chordoma at 10 participating centers. Radiological and neurological outcomes were assessed after SRS, and predictive factors were evaluated via statistical methodology. RESULTS: A total of 93 patients (56 males [60.2%], mean age 44.8 years [SD 16.6]) underwent single-session SRS for intracranial chordoma. SRS was utilized as adjuvant treatment in 77 (82.8%) cases, at recurrence in 13 (14.0%) cases, and as primary treatment in 3 (3.2%) cases. The mean tumor volume was 8 cm3 (SD 7.3), and the mean prescription volume was 9.1 cm3 (SD 8.7). The mean margin and maximum radiosurgical doses utilized were 17 Gy (SD 3.6) and 34.2 Gy (SD 6.4), respectively. On multivariate analysis, treatment failure due to tumor progression (p = 0.001) was associated with an increased risk for post-SRS neurological deterioration, and a maximum dose > 29 Gy (p = 0.006) was associated with a decreased risk. A maximum dose > 29 Gy was also associated with improved local tumor control (p = 0.02), whereas the presence of neurological deficits prior to SRS (p = 0.04) and an age > 65 years at SRS (p = 0.03) were associated with worse local tumor control. The 5- and 10-year tumor progression-free survival rates were 54.7% and 34.7%, respectively. An age > 65 years at SRS (p = 0.01) was associated with decreased overall survival. The 5- and 10-year overall survival rates were 83% and 70%, respectively. CONCLUSIONS: SRS appears to be a safe and relatively effective adjuvant management option for intracranial chordomas. The best outcomes were obtained in younger patients without significant neurological deficits. Further well-designed studies are necessary to define the best timing for the use of SRS in the multidisciplinary management of intracranial chordomas.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). CONCLUSIONS: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Clinical and radiologic outcomes after stereotactic radiosurgery for meningiomas in direct contact with the optic apparatus: an international multicenter study.

OBJECTIVE: Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus. METHODS: The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression. RESULTS: SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9-1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0-1.02, adjusted p = 0.02). CONCLUSIONS: In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.

Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study.

BACKGROUND: Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. OBJECTIVE: To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. METHODS: We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). RESULTS: The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%,  < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013). CONCLUSION: Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role.

Stereotactic Radiosurgery for Olfactory Groove Meningiomas: An International, Multicenter Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs). OBJECTIVE: To investigate the safety and efficacy of SRS for OGMs. METHODS: From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS. RESULTS: In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001). CONCLUSION: SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

PURPOSE: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial. METHODS AND MATERIALS: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis. RESULTS: Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm3 (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm3, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%). CONCLUSIONS: SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas. OBJECTIVE: To study the safety and effectiveness of SRS for perioptic meningiomas. METHODS: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus. RESULTS: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline. CONCLUSION: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study.

BACKGROUND: Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described. OBJECTIVE: To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs. METHODS: An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS: A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively. CONCLUSION: AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.

Evaluating and reducing xerosis in competitive swimmers: an in vitro study and randomized controlled clinical trial.

INTRODUCTION: Xerosis is a common problem with significant sequelae in competitive swimmers, and it results from transepidermal water loss. This study evaluates moisture barriers for reducing xerosis in competitive swimmers. METHODS: An artificial skin model was used to evaluate five products. Models were measured for changes in thickness and weight over 7 days. The optimal barrier was tested in a randomized controlled trial (RCT) of 20 swimmers. Skin moisture content was serially measured. Skin micrographs were scored in a blinded fashion. RESULTS: The moisture barrier #1 treated skin model at day 7 maintained a mean thickness of 7.08 mm versus 2.38 mm for control (p = .0001). The mean weights of group 1 treated and control groups at day 7 were 40.1 and 8.65 g (p = .03). In the RCT, the group treated with moisture barrier #1 and the controls exhibited low moisture content and moderate xerosis scores at baseline. At week 3, moisture measurements for treated and control groups were 28.6% and 18.2% (p = .003). The mean xerosis scores for the treated and control groups were 8.5 and 12.9 (p = .0008). CONCLUSIONS: Artificial skin preservation varied for five commercially available moisture barriers. Moisture barrier application improved moisture content and reduced xerosis in competitive swimmers.

Stereotactic radiosurgery for acromegaly: an international systematic review and meta-analysis of clinical outcomes.

INTRODUCTION: We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). METHODS: Primary outcomes were 5- and 10-year endocrine remission (ER) and endocrine control (EC). Secondary outcomes were 10-year radiographic local control (LC), visual toxicity, and hypopituitarism rates. Weighted random effects meta-analyses using the DerSimonian and Laird methods were conducted to characterize and compare effect sizes. Mixed effects regression models were used to examine correlations between potential prognostic factors and primary and secondary outcomes. RESULTS: In total, 1533 patients across 20 published studies with acromegaly treated with SRS were included. At 5-years, estimated ER and EC rates were 43.2% (95% CI 31.7-54.6%) and 55.0% (95% CI 27.6-82.4%), respectively. At 10-years, estimated ER and EC rates were 56.9% (95% CI 47.5-66.4%) and 69.7% (95% CI 47.7-91.8%), respectively. The estimated 10-year LC rate was 92.8% (95% CI 83.0-100%). Visual toxicity and hypopituitarism following SRS were estimated to be 2.7% (95% CI 1.3-4.2%) and 26.8% (95% CI 16.9-36.7%), respectively. Every 1 Gy increase in margin prescription dose beyond 17 Gy was estimated to result in a 0.41% increased risk of visual toxicity (p = 0.03). No prognostic factors were associated with EC, ER, LC, or hypopituitarism. CONCLUSIONS: SRS was well-tolerated in the management of pituitary acromegaly resulting in gradually improving ER and EC rates over time that approached 60% and 70%. SRS-related visual loss is an uncommon treatment-related side effect, and patient-specific clinical decision making remains critical.

Investigation of the tumoricidal effects of sonodynamic therapy in malignant glioblastoma brain tumors.

OBJECTIVE: Glioblastoma is the most common primary brain tumor; survival is typically 12-18 months after diagnosis. We sought to study the effects of sonodynamic therapy (SDT) using 5-Aminolevulinic acid hydrochloride (5-ALA) and high frequency focused ultrasound (FUS) on 2 glioblastoma cell lines. PROCEDURE: Rat C6 and human U87 glioblastoma cells were studied under the following conditions: 1 mM 5-ALA (5-ALA); focused ultrasound (FUS); 5-ALA and focused ultrasound (SDT); control. Studied responses included cell viability using an MTT assay, microscopic changes using phase contract microscopy, apoptotic induction through a caspase-3 assay, and apoptosis staining to quantify cell death. RESULTS: SDT led to a marked decrease in cell extension and reduction in cell size. For C6, the MTT assay showed reductions in cell viability for 5-ALA, FUS, and SDT groups of 5%, 16%, and 47%, respectively compared to control (p < 0.05). Caspase 3 induction in C6 cells relative to control showed increases of 109%, 110%, and 278% for 5-ALA, FUS, and SDT groups, respectively (p < 0.05). For the C6 cells, caspase 3 staining positivity was 2.1%, 6.7%, 11.2%, and 39.8% for control, 5-ALA, FUS, and SDT groups, respectively. C6 Parp-1 staining positivity was 1.9%, 6.5%, 9.0%, and 37.8% for control, 5-ALA, FUS, and SDT groups, respectively. U87 cells showed similar responses to the treatments. CONCLUSIONS: Sonodynamic therapy resulted in appreciable glioblastoma cell death as compared to 5-ALA or FUS alone. The approach couples two already FDA approved techniques in a novel way to treat the most aggressive and malignant of brain tumors. Further study of this promising technique is planned.