Faculty Bibliography

OBJECTIVE:Stereotactic radiosurgery (SRS) has long been used for the management of vestibular schwannoma (VS). While the use of SRS as a primary or adjuvant modality for VS has been extensively studied, more effort is needed to clarify the outcomes of SRS as a salvage approach after tumor progression following incomplete resection of VS. The objective of this study was to determine the safety and efficacy of salvage SRS for tumor progression after incomplete resection of VS and to elucidate the factors influencing tumor control and freedom from additional treatment (FFAT). METHODS:Patients with VS who underwent incomplete microsurgical resection followed by salvage SRS for tumor progression were retrospectively reviewed. A total of 64 patients were identified and analyzed. The median patient age at time of SRS was 51.5 years, and 30 (46.9%) patients were males. The median marginal dose was 12.5 Gy at a median isodose of 50%. RESULTS:The 10- and 15-year tumor control rates following salvage SRS were 87.5% (95% CI 76.8-94.4) and 84.4% (95% CI 73.1-92.2), respectively, while the 10- and 15-year FFAT rates were 95.3% (95% CI 86.9-99.0) and 92.2% (95% CI 82.7-97.4), respectively. No factors were significantly associated with tumor control or FFAT in the Cox proportional hazards model. The median time between microsurgical resection and salvage SRS was 38.8 months. Following SRS, the primary complication was worsening or new-onset trigeminal neuropathy (n = 10 [15.6%]). Worsening hearing, measured using Gardner-Robertson class, was reported in 9 cases (14.1%). CONCLUSIONS:Salvage SRS is a safe and effective modality for long-term tumor control and FFAT in VS patients whose tumors progress after initial incomplete microsurgical resection.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Trigeminal schwannomas (TSs) are rare, mostly benign tumors that exhibit an indolent clinical course. The lateral orbitotomy approach (LOA), with or without endoscopic assistance, has emerged as a novel skull base route, particularly for accessing lesions confined to the middle cranial fossa. Herein, we elucidate the advantages and limitations of the LOA for the treatment of TSs. METHODS:All TS cases that underwent LOA through a lateral canthus incision during the past decade in our department were retrospectively reviewed. The operative technique was detailed, and clinical outcomes were analyzed. RESULTS:Eight patients (4 females) with an average age of 37 years underwent LOA for TSs. The mean maximum tumor diameter was 2.7 cm (range: 1.8-3.7 cm). Seven were primary and one was recurrent, the latter in a patient with neurofibromatosis type 2. All tumors were predominantly in the middle cranial fossa, with 4 having either a small or medium posterior fossa component (6: Samii Type A; 2: Type C). Presenting symptoms included trigeminal neuralgia (n = 6), facial hypoesthesia (n = 6), headache (n = 5), and double vision (n = 3). All patients underwent gross (n = 6) or near-total (n = 2) resection. Neuralgia, while not exacerbated, reappeared in 4 patients after surgery and was ameliorated with medication. Two patients sustained new trigeminal hypoesthesia, and preoperative abducens palsy either improved or resolved in all 3 cases. No orbital complications, cerebrospinal fluid leak, or mortalities occurred. Two lesions had minor recurrence during a mean follow-up of 42.9 months. The first underwent radiosurgery 6 years postoperatively and the second is under close surveillance. CONCLUSION/CONCLUSIONS:Minimally invasive LOA stands as a plausible and aesthetically favorable surgical corridor for addressing TSs of the middle cranial fossa, even with extension into the posterior fossa. However, additional study is required as the approach may be limited for tumors with significant posterior or infratemporal fossa involvement.

IMPORTANCE/UNASSIGNED:Adjuvant radiotherapy can improve locoregional control and survival in patients with olfactory neuroblastoma (ONB), particularly with advanced-stage and histologic-grade disease. Standard radiotherapy treatment is with intensity-modulated radiotherapy (IMRT). Proton beam radiotherapy (PBRT) provides theoretical advantages in greater sparing of dose to uninvolved organs at risk. OBJECTIVE/UNASSIGNED:To investigate if there are differences in the effectiveness and radiation treatment-related adverse events (RTAEs) between adjuvant IMRT and PBRT for patients with ONB. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This propensity score-matched cohort study included patients with ONB treated between February 2005 and April 2021 with either IMRT or PBRT at 9 academic tertiary care centers in North America. Patients were matched 1:2 based on age, modified Kadish stage, and Hyams grade. Data were analyzed from July 2024 to January 2025. EXPOSURE/UNASSIGNED:Adjuvant IMRT or adjuvant PBRT. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Local recurrence-free survival (RFS), any RFS, and overall survival (OS). RTAEs, ie, grade 2 events or higher based on Common Terminology Criteria for Adverse Events, were recorded for both modalities. RESULTS/UNASSIGNED:Of 54 included patients, 27 (50%) were female, and the mean (SD) age was 46.2 (15.4) years. A total of 18 were treated with PBRT and 36 were treated with IMRT. Most patients had modified Kadish stage C disease (33 of 54 [61%]), and 24 patients (44%) had Hyams grade III or IV disease. The RTAE rate was 20% (8 of 40); IMRT had a rate of 21% (6 of 29), and PBRT had a rate of 18% (2 of 11). The difference in the point estimates for 10-year RFS showed a potential clinical benefit favoring IMRT, although the wide confidence interval indicates uncertainty (10-year RFS: IMRT, 63.3%; 95% CI, 44.6-89.8; PBRT, 37.8%; 95% CI, 14.2-100; difference, 25.5 percentage points; 95% CI, -17.6 to 68.6). There were no clinically meaningful differences in 10-year local RFS (IMRT, 75.6%; 95% CI, 59.8-95.4; PBRT, 72.7%; 95% CI, 45.2-100; difference, 2.9 percentage points; 95% CI, -35.9 to 41.7) or 10-year OS (IMRT, 61.8%; 95% CI, 42.8-89.1; PBRT, 57.1%; 95% CI, 24.3-100; difference, 4.7 percentage points; 95% CI, -49.2 to 58.6), although wide confidence intervals indicate considerable uncertainty. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Due to the imprecision of estimates, no definitive conclusions can be made regarding the comparative effectiveness of IMRT vs PBRT for patients with ONB. These preliminary data may inform the design of appropriately powered prospective studies evaluating the efficacy of PBRT vs IMRT in this population.

PURPOSE/OBJECTIVE:Clinical screening systems (CSSs) for Cushing syndrome (CS) validated in Europe have not been evaluated for CS or Cushing disease (CD) in the United States (US). We aimed to evaluate existing CSSs in US patients and develop two new symptom-based CSSs to identify patients with high pre-test probability of disease warranting referral for definitive biochemical workup-one for broad CS screening and one specifically for CD. METHODS:Data were obtained from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID)-comprising 615 patients who underwent transnasal transsphenoidal resection for CD at one of 11 US pituitary centers, the Centers for Disease Control and Prevention's 2019 National Health Interview Survey (NHIS)-comprising 31,997 US respondents, and a single institution CD-NFA cohort-comprising 468 US patients diagnosed with either CD (n = 385) or nonfunctioning adenoma (n = 83). The RAPID Community Cushing CSS was derived from differences between the RAPID and NHIS cohorts, and the RAPID CD CSS from differences between patients with CD versus NFA. RESULTS:In external validation using US-based cohorts, the RAPID Community CSS achieved an AUC of 0.707, compared to the Spanish (AUC = 0.691) and Italian (AUC = 0.685) models, and the RAPID CD CSS demonstrated greater external sensitivity (0.836, threshold = 0.5) at the Youden-optimized threshold than the Spanish (0.605, threshold = 4) and Italian (0.735, threshold = 6) CSSs. CONCLUSIONS:In US patient populations, the RAPID Community Cushing CSS demonstrated superior discriminative ability for CD compared to the Italian and Spanish CSSs, and the RAPID CD CSS achieved the highest sensitivity for CD among all CSSs evaluated.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Tuberculum sellae meningiomas (TSMs) can be resected through transcranial (TCA) or expanded endonasal approach (EEA). The objective of this study was to report TSM management trends and outcomes in a large multicenter cohort. METHODS:This is a 40-site retrospective study using standard statistical methods. RESULTS:In 947 cases, TCA was used 66.4% and EEA 33.6%. The median maximum diameter was 2.5 cm for TCA and 2.1 cm for EEA ( P < .0001). The median follow-up was 26 months. Gross total resection (GTR) was achieved in 70.2% and did not differ between EEA and TCA ( P = .5395). Vision was the same or better in 87.5%. Vision improved in 73.0% of EEA patients with preoperative visual deficits compared with 57.1% of TCA patients ( P < .0001). On multivariate analysis, a TCA (odds ratio [OR] 1.78, P = .0258) was associated with vision worsening, while GTR was protective (OR 0.37, P < .0001). GTR decreased with increased diameter (OR: 0.80 per cm, P = .0036) and preoperative visual deficits (OR 0.56, P = .0075). Mortality was 0.5%. Complications occurred in 23.9%. New unilateral or bilateral blindness occurred in 3.3% and 0.4%, respectively. The cerebrospinal fluid leak rate was 17.3% for EEA and 2.2% for TCA (OR 9.1, P < .0001). The recurrence rate was 10.9% (n = 103). Longer follow-up (OR 1.01 per month, P < .0001), World Health Organization II/III (OR 2.20, P = .0262), and GTR (OR: 0.33, P < .0001) were associated with recurrence. The recurrence rate after GTR was lower after EEA compared with TCA (OR 0.33, P = .0027). CONCLUSION/CONCLUSIONS:EEA for appropriately selected TSM may lead to better visual outcomes and decreased recurrence rates after GTR, but cerebrospinal fluid leak rates are high, and longer follow-up is needed. Tumors were smaller in the EEA group, and follow-up was shorter, reflecting selection, and observation bias. Nevertheless, EEA may be superior to TCA for appropriately selected TSM.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Tuberculum sellae meningiomas are resected via an expanded endonasal (EEA) or transcranial approach (TCA). Which approach provides superior outcomes is debated. The Magill-McDermott (M-M) grading scale evaluating tumor size, optic canal invasion, and arterial involvement remains to be validated for outcome prediction. The objective of this study was to validate the M-M scale for predicting visual outcome, extent of resection (EOR), and recurrence, and to use propensity matching by M-M scale to determine whether visual outcome, EOR, or recurrence differ between EEA and TCA. METHODS:Forty-site retrospective study of 947 patients undergoing tuberculum sellae meningiomas resection. Standard statistical methods and propensity matching were used. RESULTS:The M-M scale predicted visual worsening (odds ratio [OR]/point: 1.22, 95% CI: 1.02-1.46, P = .0271) and gross total resection (GTR) (OR/point: 0.71, 95% CI: 0.62-0.81, P < .0001), but not recurrence ( P = .4695). The scale was simplified and validated in an independent cohort for predicting visual worsening (OR/point: 2.34, 95% CI: 1.33-4.14, P = .0032) and GTR (OR/point: 0.73, 95% CI: 0.57-0.93, P = .0127), but not recurrence ( P = .2572). In propensity-matched samples, there was no difference in visual worsening ( P = .8757) or recurrence ( P = .5678) between TCA and EEA, but GTR was more likely with TCA (OR: 1.49, 95% CI: 1.02-2.18, P = .0409). Matched patients with preoperative visual deficits who had an EEA were more likely to have visual improvement than those undergoing TCA (72.9% vs 58.4%, P = .0010) with equal rates of visual worsening (EEA 8.0% vs TCA 8.6%, P = .8018). CONCLUSION/CONCLUSIONS:The refined M-M scale predicts visual worsening and EOR preoperatively. Preoperative visual deficits are more likely to improve after EEA; however, individual tumor features must be considered during nuanced approach selection by experienced neurosurgeons.

OBJECTIVE:Skull base chordoma is a rare and locally destructive malignancy which presents unique therapeutic challenges. While achieving gross total resection (GTR) confers the greatest survival advantage, the role of adjuvant radiotherapy (RT) for patients who receive GTR remains unclear in the absence of prospective trials. Here, we aim to assess the effect of RT on survival outcomes in skull base chordoma patients who receive GTR by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS:Patients with diagnostic, primary site, and resection codes specific for chordoma, skull base, and GTR, respectively, were queried in the SEER database (2000-2018). Kaplan-Meier curves (log-rank test) were constructed and Cox proportional hazards models were used to assess survival outcomes. RESULTS:A total of 115 skull base chordomas undergoing GTR were identified, of which 37 (32%) received no RT and 78 (68%) received RT. Median follow-up was 55.00 months (range: 0.00-227.00). Overall survival (OS) of patients with GTR was 85% and 70% at 5 and 10 years, respectively. Multivariate Cox proportional hazard analysis among chordoma patients undergoing GTR found age ≥65 (P < 0.01) was associated with poorer OS outcomes. RT appeared to trend toward offering benefit in terms of OS in patients after GTR, however this did not achieve statistical significance in the adjusted model (HR = 0.51, CI = 0.23-1.16, P = 0.09). When comparing, disease-specific survival was also not improved in patients undergoing RT (HR = 0.58, CI = 0.23-1.46, P = 0.25). CONCLUSIONS:It remains unclear whether RT after GTR of chordoma improved survival outcomes among SEER database patients.

OBJECTIVE:Prealbumin levels correlate with overall nutritional status, and low values are associated with poor wound healing. We investigated whether low preoperative prealbumin levels predict risk of endoscopic endonasal skull base surgery (EESBS) reconstruction failure, as demonstrated by postoperative cerebrospinal fluid (CSF) leak and/or infection. METHODS:Between October 2018 and February 2020, 98 patients with documented preoperative prealbumin levels were prospectively followed. The incidence of CSF leak and infection in patients with low prealbumin levels (≤20 mg/dL) was compared with those with normal prealbumin levels (>20 mg/dL). Numerous factors previously shown to influence CSF leak rates were assessed. Both univariate and multivariable analyses were performed to identify independent predictive factors. RESULTS:Within this prospectively gathered patient cohort composed of >95% "high-risk" expanded EESBS, 14 of 98 patients (14.3%) experienced a postoperative CSF leak. Factors univariately associated with postoperative complications at the 0.2 level of significance were used in a multivariable model. Low prealbumin levels (≤20 mg/dL) proved to be a strong independent predictive factor associated with a 5-fold increased risk of postoperative CSF leak (odds ratio 5.01, P = 0.01), and postoperative surgical-site infection (P = 0.0009). These associations remained after controlling for multiple other factors, including body mass index, surgical pathology, previous EESBS, risk assessment index, and high- versus low-flow intraoperative CSF leaks. CONCLUSIONS:Preoperative prealbumin levels are an independent predictor of EESBS associated CSF leak and infection. Future studies are needed to investigate the utility of screening and correcting prealbumin levels to limit postoperative complications.