Link, Michael J.

OBJECTIVE Brain metastases significantly impact neurocognitive function and overall survival. Stereotactic radiosurgery (SRS) is a cornerstone of treatment for patients with limited metastases and expected survival beyond 3 months. Despite current guidelines, up to 20% of patients with brain metastases undergoing SRS have been reported to die within 90 days. This study retrospectively evaluated prognostic factors associated with 90-day survival after SRS, aiming to improve patient selection. METHODS The authors retrospectively analyzed a cohort of 1546 patients who underwent Gamma Knife SRS for brain metastases at their institution between 2015 and 2023. One hundred seventy patients who survived less than 90 days after SRS were identified and case matched to 170 patients who survived over 90 days. Measured variables included patient demographic characteristics, tumor characteristics, treatment history, functional status, and control of the primary cancer. The authors modeled post-SRS 90-day survival using binomial and multivariate logistic regression. RESULTS Multivariate analysis highlighted Karnofsky Performance Score (KPS) < 70 (OR 17.4, p < 0.001), prior whole-brain radiation (OR 6, p = 0.004), and focal neurological deficits (OR 3.02, p = 0.003) as significant predictors of poor survival, whereas CNS progression before SRS (OR 0.22, p < 0.001) and control of systemic cancer (OR 0.556, p = 0.002) were associated with survival < 90 days. The predictive model demonstrated acceptable performance with an area under the curve (AUC) of 0.85, accuracy of 80%, sensitivity of 87%, and specificity of 71%. CONCLUSIONS Key predictors of 90-day survival after SRS for brain metastases include functional status (KPS), control of systemic cancer, CNS progression status, and focal neurological deficits. These findings are complementary factors that can assist in making decisions and SRS patient selection.

Abstract Brain metastases significantly impact neurocognitive function and overall survival. Stereotactic radiosurgery (SRS) is a cornerstone of treatment for patients with limited metastases and expected survival beyond three months. Despite current guidelines, up to 20% of patients with brain metastases undergoing SRS have been reported to die within 90 days. This study retrospectively evaluates prognostic factors associated with 90-day survival after SRS, aiming to improve patient selection. We retrospectively analyzed a cohort of 1,546 patients who underwent Gamma Knife SRS for brain metastases at our institution between 2015 and 2023. One hundred seventy patients who survived fewer than 90 days post-SRS were identified and case-matched to 170 patients who survived over 90 days. Measured variables included patient demographics, tumor characteristics, treatment history, functional status, and control of the primary cancer. We modeled post-SRS 90-day survival using binomial and multivariate logistic regression. Multivariate analysis highlighted Karnofsky Performance Status (KPS) &lt; 70 (OR: 17.4, p &lt; 0.001), prior whole brain radiation (OR: 6, p = 0.004), and focal neurological deficits (OR: 3.02, p = 0.003) as significant predictors of early deaths, while CNS progression before SRS (OR: 0.22, p &lt; 0.001) and control of systemic cancer (OR: 0.556, p = 0.002) were associated with a less than 90-day survival. The predictive model demonstrated acceptable performance with an area under the curve (AUC) of 0.85, accuracy of 80%, sensitivity of 87%, and specificity of 71%. Key predictors of 90-day survival following SRS for brain metastases include functional status (KPS), control of systemic cancer, CNS progression status, and focal neurologic deficits. These findings are complementary factors that can assist in making decisions and SRS patient selection.

Objective: Vestibular schwannomas (VSs) treated with stereotactic radiosurgery (SRS) often show transient loss of central tumor enhancement. We hypothesized that this loss of enhancement may correlate with better tumor control on follow-up imaging. Methods: We evaluated 198 consecutive patients from a single center who met eligibility criteria. Tumor volumes on the pre-SRS and post-SRS scans were quantified along with regions of loss of enhancement on the first post-SRS study. The latter was correlated with tumor volumes at follow-up, radiation isocenter density, and loss of serviceable hearing. Results: For the entire cohort, the median loss of enhancement on the first post-SRS scan was 14% (IQR: 6 to 25) and median rate of change in tumor volume was −4.5% per year (IQR: −10.5 to 1.5). Percent loss of central enhancement showed significant negative correlation with tumor growth not only for the entire cohort (correlation coefficient: −0.18, P =0.01), but also for the subset of patients who had available imaging until at least 2 years (n=185) and 4 years (n=179) post-SRS. Loss of enhancement also strongly correlated positively with tumor volumes and number of radiation isocenters and negatively with isocenter density. Finally, patients with greater percent loss of enhancement had an increased likelihood of progression to non-serviceable hearing, although this association was not statistically significant. Conclusions: These findings suggest that loss of central tumor enhancement in VSs post-SRS may be associated with improved tumor control.

BACKGROUND AND OBJECTIVES: Surgery in NF2-related schwannomatosis (NF2-SWN) vestibular schwannoma (VS) carries a higher risk of facial nerve damage, hearing loss, and partial resection, than in sporadic cases. Radiosurgery is also associated with higher failure compared with sporadic schwannomas. Nowadays, bevacizumab (BEV) is frequently considered in the NF2-SWN population. However, some patients experience progression despite treatment. Among other surgical risks, in BEV-treated patients, hemorrhage and impaired healing are specific considerations. These concerns have led manufacturers to recommend stopping BEV 6 to 8 weeks preoperatively. The aim of our multicentric study was to assess the perioperative bleeding risk and postoperative outcomes in NF2-SWN patients undergoing VS surgery after preoperative BEV treatment. METHODS: Our retrospective analysis included medical and surgical records along with imaging reviews from 4 high-volume tertiary academic referral centers for NF2-SWN and VS. RESULTS: A total of 21 patients met the inclusion criteria. VS had a mean volume of 13.2 ±7.6 cm 3 corresponding to 1 KOOS III and 20 KOOS IV. BEV was stopped at a mean of 5.8 ± 4.0 months before surgery with a total mean treatment duration of 33.7 ± 20.7 months and a monthly dose of 10.2 ± 4.1 mg/kg. Intraoperatively, the tumor was assessed to be bloody by the operating surgeons in 7 patients. Late BEV discontinuation and high cumulative dose independently predicted perioperative bleeding and longer surgery duration. No other complication such as wound dehiscence was reported. CONCLUSION: Our findings suggest that a higher cumulative BEV dose (∼600 mg/kg) and a longer interval between BEV discontinuation and surgery (∼8 months) are associated with a modest but statistically significant increase in intraoperative bleeding risk. Based on these observations, a BEV-free window between 6 weeks and 6 months (depending on the clinical scenario) before tumor resection seems optimal, particularly for patients with high cumulative exposure.

BACKGROUND AND OBJECTIVE: In skull base surgery, endoscopic endonasal approaches require precise evaluation of the area of exposure and the maneuverability provided by each approach. Current neuroanatomical methodologies for quantifying these parameters primarily rely on computed tomography (CT) scans and neuronavigation systems, which entail significant financial investment. The aim of this study was to develop and validate an innovative, cost-effective methodology using an endoscopic photogrammetric model to measure the exposure area and maneuverability in endoscopic endonasal approaches, offering an accessible alternative to existing techniques. METHODS: Six cadaveric specimens were used to validate the accuracy of endoscopic photogrammetric measurements by comparing them with direct measurements. Subsequently, the exposure area, angle of attack, and surgical freedom were analyzed for 3 endoscopic approaches to the parasellar region: contralateral transmaxillary, single-nostril, and double-nostril approaches. RESULTS: Photogrammetric measurements demonstrated a high level of concordance with direct cadaveric measurements, with a mean difference of 0.02 mm as shown in the Bland-Altman plot. In addition, measurements obtained in comparative analysis describing the exposure area and maneuverability of 3 endoscopic approaches were congruent with those reported in existing literature derived using CT scans and neuronavigation systems. CONCLUSION: To our knowledge, this study is the first to validate endoscopic photogrammetric models as a measurement tool in neuroanatomy. Performing direct measurements on 3D models might eliminate the necessity of expensive CT and neuronavigation systems for volumetric quantification. Our cost-effective methodology allows for the widespread democratization of anatomical quantification within skull base neuroanatomy.

AbstractObjectiveTo examine associations with changes in quality‐of‐life (QOL) outcomes following treatment of vestibular schwannoma (VS) using stereotactic radiosurgery (SRS).Study DesignProspective longitudinal study.SettingTertiary academic center.MethodsPatients who were treated for sporadic VS using SRS from 2015 to 2022 were included. QOL outcomes were measured using the disease‐specific Penn Acoustic Neuroma QOL (PANQOL) scale.ResultsSeventy‐nine patients with pre‐SRS and at least one post‐SRS PANQOL assessments were available for analysis. The mean change in total PANQOL scores was −2 (SD 13) on a 100‐point scale. The mean duration between assessments was 4.6 years (SD 2.0). Age at SRS, sex, and SRS treatment doses were not significantly associated with changes in total PANQOL scores. Total PANQOL scores improved a mean of 4 points for patients with tumors confined to the internal auditory canal but declined a mean of 5 points for patients with tumors extending into the cerebellopontine angle (P = .01); however, these changes did not exceed the minimum clinically significant threshold of 11 points. The correlation coefficient between treated tumor volume at SRS and change in total PANQOL scores was −0.30 (P = .007). Changes in PANQOL total (P = .5) and hearing domain (P = .3) scores for patients who maintained serviceable hearing or progressed to nonserviceable hearing did not significantly differ.ConclusionTumor extent and treated volume at SRS had a statistically significant but likely not clinically important impact on total PANQOL scores. Progression to nonserviceable hearing did not have a significant impact on PANQOL total or hearing domain scores.

Objective To compare differences in sporadic vestibular schwannoma (VS)–associated patient-reported symptom scores among patients receiving observation, microsurgery, or radiosurgery. Study Design Prospective longitudinal survey. Setting Tertiary referral center and the national Acoustic Neuroma Association. Patients Adults with sporadic VS. Intervention Observation, microsurgery, or radiosurgery. Main Outcome Measure Baseline and follow-up surveys on patient-reported severity of tinnitus, dizziness/imbalance, and headaches scored on a 10-point numeric scale, with higher scores indicating more severe symptoms; changes of 2 or more points from baseline were considered clinically important. Results A total of 455 patients were eligible for study with a mean (SD) follow-up of 4.5 (2.4) years, including 122 (27%) managed with observation, 226 (50%) undergoing microsurgery, and 107 (23%) undergoing radiosurgery. Changes in tinnitus severity scores differed significantly among management groups (p = 0.006), with severity scores increasing significantly in the radiosurgery (+0.8, p = 0.005) group but not in the observation (+0.2, p = 0.5) or microsurgery (−0.2, p = 0.18) groups. The changes in dizziness/imbalance and headache severity scores did not differ significantly among management groups. When comparing clinically important improvements (decrease of 2 or more points), the microsurgery and observation cohorts had a greater proportion of patients experiencing a clinically important improvement in tinnitus compared with the radiosurgery cohort; no other clinically important changes were significantly different among management groups. Conclusions In this prospective study of 455 patients comparing patient-reported symptoms after VS management, radiosurgery was associated with worsening tinnitus severity scores overall and resulted in fewer patients reporting clinically important improvements in tinnitus compared with observation and microsurgery. As there was substantial variability in the effect of management modality on changes in symptom severity scores, possible treatment effects on subjective symptoms, including tinnitus, dizziness/imbalance, and headache, should not be used in isolation to inform clinical decision-making for management of sporadic VS.

BACKGROUND AND OBJECTIVES: Schwannomas are benign, slow-growing peripheral nerve sheath tumors. Approximately 8% of intracranial schwannomas originate from the trigeminal nerve. No consensus exists regarding superiority of outcomes after resection vs stereotactic radiosurgery (SRS) in the treatment of trigeminal schwannomas (TS). The aim of this study was to compare the efficacy and outcomes of resection vs SRS for TS management. METHODS: Embase, PubMed, and SCOPUS databases were queried from the date of inception to July 2023 for primary data reporting TS treatment outcomes after SRS or resection. Risk of bias was reported under Newcastle-Ottawa Scale. RESULTS: Overall, 29 retrospective observational studies comprising 949 patients were included in the analysis. A total of 13 studies (n = 589) reported outcomes after SRS, and 16 studies (n = 360) reported outcomes after surgical resection, and 182 patients in the SRS group had previous resection. To ensure statistical validity of comparing the cohorts, 3 checkpoints were assessed: the median age (SRS: 48 vs surgery: 40 years old, P < .01), tumor volume (5.2 vs 8.9 cm 3 , P = .06), and median follow-up (53.9 vs 48.5 months, P = .59), which reflected the choice of treatment. Compared with surgical resection, the SRS group demonstrated significantly higher rates of facial hypesthesia improvement (44% vs 12%, P < .01) and lower rates of new onset (4% vs 15%, P = .051) at last follow-up. Facial pain was less likely to improve (58% vs 81%, P = .024) after SRS compared with surgery. However, worsened (5% vs 1%, P = .71) and new facial pain (2% vs 1%, P = .55) were comparable between cohorts. CONCLUSION: SRS seems to offer improvement in rates of hypesthesia and trigeminal motor deficits compared with surgical resection for TS. However, facial pain improvement was more favorable after surgery. These findings highlight the importance of individualized treatment decisions based on patient characteristics, tumor profile, and pretreatment symptoms.

AbstractObjectiveLimited evidence guides the optimal timing of treatment after the detection of tumor growth during the observation of sporadic vestibular schwannoma (VS). The current work aimed to inform the timing of radiosurgical intervention based on an analysis of patient outcomes among those who ultimately failed stereotactic radiosurgery (SRS) and underwent salvage microsurgery.Study DesignA historical cohort study.SettingSeven centers across the United States and Norway.MethodsAdults with sporadic VS who underwent salvage microsurgery following failed primary SRS were included. The primary outcome of interest was the association between tumor size at the time of primary SRS and the ability to achieve gross total resection (GTR) and maintain postoperative House–Brackmann (HB) facial nerve grade I at the last follow‐up after salvage microsurgery.ResultsAmong 96 patients, the median (interquartile range [IQR]) cerebellopontine angle (CPA) tumor size at primary SRS was 14.5 mm (10.0‐19.0). Each 1‐mm increase in CPA tumor size at the time of primary SRS was associated with a 13% increased likelihood of near‐total/subtotal resection or most recent postoperative HB grade >I (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05‐1.21, P = .001), with an optimal tumor size threshold to distinguish this outcome of 12 mm of CPA extension (c‐index 0.73). Similarly, for each 1‐mm increase in CPA tumor size at the time of primary SRS, a 9% increase in any postoperative complication with salvage microsurgery was observed (OR 1.09, 95% CI 1.02‐1.15, P = .009).ConclusionCorroborated by size threshold surveillance data informing the timing of primary microsurgical resection, the current study suggests that VS outcomes are optimized when primary radiosurgical intervention is undertaken on growing tumors when they harbor 10–15 mm of cerebellopontine angle extension or less.