Sheehan, Jason P.

Abstract Background The choice of an appropriate strategy for intracanalicular vestibular schwannoma (ICVS) is still debated. We conducted a systematic review and meta-analysis with the aim to compare treatment outcomes amongst management strategies (conservative surveillance (CS), microsurgical resection (MR), or stereotactic radiosurgery (SRS)) aiming to inform guideline recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). Methods Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2021 referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies or case series reporting a cohort of ICVS managed with CS, MR, or SRS. Primary outcome measures included tumor control, the need for additional treatment, hearing outcomes, and posttreatment neurological deficits. These were pooled using meta-analytical techniques and compared using meta-regression with random effect. Results Forty studies were included (2371 patients). The weighted pooled estimates for tumor control were 96% and 65% in SRS and CS series, respectively (P < .001). Need for further treatment was reported in 1%, 2%, and 25% for SRS, MR, and CS, respectively (P = .001). Hearing preservation was reported in 67%, 68%, and 55% for SRS, MR, and CS, respectively (P = .21). Persistent facial nerve deficit was reported in 0.1% and 10% for SRS and MR series, respectively (P = .01). Conclusions SRS is a noninvasive treatment with at least equivalent rates of tumor control and hearing preservation as compared to MR, with the caveat of better facial nerve preservation. As compared to CS, upfront SRS is an effective treatment in achieving tumor control with similar rates of hearing preservation.

BACKGROUND AND OBJECTIVES: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs. METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed. RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09) CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

OBJECTIVE The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM). METHODS Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22–8.1 cm3), and the median margin dose was 20 Gy (IQR 18–22 Gy). RESULTS The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4–4.9; p = 0.003 and HR 3.4, 95% CI 1.7–6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19–0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1–2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1–2.4; p = 0.009) were significantly associated with worse OS. CONCLUSIONS Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

OBJECTIVE The literature on non–small cell lung cancer (NSCLC) brain metastases (BMs) managed using stereotactic radiosurgery (SRS) relies mainly on single-institution studies or randomized controlled trials (RCTs). There is a literature gap on clinical and radiological outcomes of SRS for NSCLC metastases in real-world practice. The objective of this study was to benchmark mortality and progression outcomes in patients undergoing SRS for NSCLC BMs and identify risk factors for these outcomes using a national quality registry. METHODS The SRS Registry of the NeuroPoint Alliance was used for this study. This registry included patients from 16 enrolling sites who underwent SRS from 2017 to 2022. Data are prospectively collected without a prespecified research purpose. The main outcomes of this analysis were overall survival (OS), out-of-field recurrence, local progression, and intracranial progression. All time-to-event investigations included Kaplan-Meier analyses and multivariable Cox regressions. RESULTS Two hundred sixty-four patients were identified, with a mean age of 66.7 years and a female proportion of 48.5%. Most patients (84.5%) had a Karnofsky Performance Status (KPS) score of 80–100, and the mean baseline EQ-5D score was 0.539 quality-adjusted life years. A single lesion was present in 53.4% of the patients, and 29.1% of patients had 3 or more lesions. The median OS was 28.1 months, and independent predictors of mortality included no control of primary tumor (hazard ratio [HR] 2.1), KPS of 80 (HR 2.4) or lower (HR 2.4), coronary artery disease (HR 2.8), and 5 or more lesions present at the time of SRS treatment (HR 2.3). The median out-of-field progression-free survival (PFS) was 24.8 months, and the median local PFS was unreached. Intralesional hemorrhage was an independent risk factor of local progression, with an HR of 6.0. The median intracranial PFS was 14.0 months and was predicted by the number of lesions at the time of SRS (3–4 lesions, HR 2.2; 5–14 lesions, HR 2.5). CONCLUSIONS In this real-world prospective study, the authors used a national quality registry and found favorable OS in patients with NSCLC BMs undergoing SRS compared with results from previously published RCTs. The intracranial PFS was mainly driven by the emergence of new lesions rather than local progression. A greater number of lesions at baseline was associated with out-of-field progression, while intralesional hemorrhage at baseline was associated with local progression.

BACKGROUND: There are limited data regarding outcomes for patients with gastrointestinal (GI) primaries and brain metastases treated with stereotactic radiosurgery (SRS). OBJECTIVE: To examine clinical outcomes after SRS for patients with brain metastases from GI primaries and evaluate potential prognostic factors. METHODS: The International Radiosurgery Research Foundation centers were queried for patients with brain metastases from GI primaries managed with SRS. Primary outcomes were local control (LC) and overall survival (OS). Kaplan-Meier analysis was used for univariate analysis (UVA) of prognostic factors. Factors significant on UVA were evaluated with a Cox multivariate analysis proportional hazards model. Logistic regressions were used to examine correlations with RN. RESULTS: We identified 263 eligible patients with 543 brain metastases. Common primary sites were rectal (31.2%), colon (31.2%), and esophagus (25.5%) with a median age of 61.6 years (range: 37-91.4 years) and a median Karnofsky performance status (KPS) of 90% (range: 40%-100%). One-year and 2-year LC rates were 83.5% (95% CI: 78.9%-87.1%) and 73.0% (95% CI: 66.4%-78.5%), respectively. On UVA, age >65 years ( P = .001), dose <20 Gy ( P = .006) for single-fraction plans, KPS <90% ( P < .001), and planning target volume ≥2cc ( P = .007) were associated with inferior LC. All factors other than dose were significant on multivariate analysis ( P ≤ .002). One-year and 2-year OS rates were 68.0% (95% CI: 61.5%-73.6%) and 31.2% (95% CI: 24.6%-37.9%), respectively. Age > 65 years ( P = .006), KPS <90% ( P = .005), and extracranial metastases ( P = .05) were associated with inferior OS. CONCLUSION: SRS resulted in comparable LC with common primaries. Age and KPS were associated with both LC and OS with planning target volume and extracranial metastases correlating with LC and OS, respectively. These factors should be considered in GI cancer patient selection for SRS.

BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

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.

Abstract Background Stereotactic radiosurgery (SRS) and resection are treatment options for patients with facial nerve schwannomas without mass effect. Objective This article evaluates outcomes of patients treated with SRS versus resection + SRS. Method We retrospectively compared 43 patients treated with SRS to 12 patients treated with resection + SRS. The primary study outcome was unfavorable combined endpoint, defined as worsening or new clinical symptoms, and/or tumor radiological progression. SRS (38.81 ± 5.3) and resection + SRS (67.14 ± 11.8) groups had similar clinical follow-ups. Results At the time of SRS, the tumor volumes of SRS (mean ± standard error; 1.83 ± 0.35 mL) and resection + SRS (2.51 ± 0.75 mL) groups were similar. SRS (12.15 ± 0.08 Gy) and resection + SRS (12.16 ± 0.14 Gy) groups received similar radiation doses. SRS group (42/43, 98%) had better local tumor control than the resection + SRS group (10/12, 83%, p = 0.04). Most of SRS (32/43, 74%) and resection + SRS (10/12, 83%) group patients reached a favorable combined endpoint following SRS (p = 0.52). Considering surgical associated side effects, only 2/10 patients of the resection + SRS group reached a favorable endpoint (p < 0.001).Patients of SRS group, who are > 34 years old (p = 0.02), have larger tumors (> 4 mL, 0.04), internal auditory canal (IAC) segment tumor involvement (p = 0.01) were more likely to reach an unfavorable endpoint. Resection + SRS group patients did not show such a difference. Conclusion While resection is still needed for larger tumors, SRS offers better clinical and radiological outcomes compared to resection followed by SRS for facial schwannomas. Younger age, smaller tumors, and non-IAC situated tumors are factors that portend a favorable outcome.

OBJECTIVE Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS. METHODS Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy. RESULTS Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70–90) and age of 57 years (IQR 48–67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03–0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18–20 Gy) to the median 71% isodose line (IQR 50%–84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis. CONCLUSIONS SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.