Neff, Brian A.

Objective(1) Assess 3‐dimensional volumetric growth of untreated sporadic vestibular schwannomas (VSs) in a large cohort of patients treated with conservative observation. (2) Compare volumetric and conventional linear diameter measurements for detecting tumor growth.Study DesignCase series with chart review.SettingTertiary skull base referral center.Subjects and MethodsPatients with sporadic VS who elected initial conservative treatment with at least 2 serial magnetic resonance imaging (MRI) scans were included. Tumor volume was determined with 3‐dimensional segmentation of MRI sequences. The volumetric threshold for tumor growth was an increase ≥20% from baseline tumor volume. Tumor size based on linear diameter was assessed with the 1995 American Academy of Otolaryngology—Head and Neck Surgery Foundation guidelines for VS outcome reporting, with growth defined as an increase ≥2 mm.ResultsA total of 361 patients were included with a median radiologic follow‐up of 4.1 years (interquartile range [IQR], 2.5‐6.8). At diagnosis, 232 VSs (64%) were purely intracanalicular, and 129 (36%) extended into the cerebellopontine angle. The median baseline tumor volume was 0.161 cm3 (IQR, 0.054‐0.418). Overall, 69% of tumors demonstrated volumetric growth at a median of 1.1 years (IQR, 0.6‐2.1) after initial MRI. In contrast, based on linear measurement assessment, 48% of tumors demonstrated growth at a median of 1.8 years (IQR, 0.8‐3.1) from first MRI scan. Disequilibrium, facial hypoesthesia, aural fullness, initial tumor size, and nonincidental diagnosis were associated with tumor growth.ConclusionThree‐dimensional volumetric assessment of VS provides a more sensitive measure of tumor growth when compared with linear diameter assessment. Through volumetric analysis, the current study revealed that a significant proportion of VSs demonstrate growth during observation.

OBJECTIVE The morbidity of gross-total resection of jugular paraganglioma (JP) is often unacceptable due to the potential for irreversible lower cranial neuropathy. Stereotactic radiosurgery (SRS) has been used at the authors’ institution since 1990 for the treatment of JP and other benign intracranial tumors. Conventional means of assessing tumor progression using linear measurements or elliptical approximations are imprecise due to the irregular shape and insinuating growth pattern of JP. The objective of this study was to assess long-term tumor control in these patients by using slice-by-slice 3D volumetric segmentation of serial MRI data. METHODS Radiographic data and clinical records were reviewed retrospectively at a single, tertiary-care academic referral center for patients treated from 1990 to 2017. Volumetric analyses by integration of consecutive tumor cross-sectional areas (tumor segmentation) of serial MRI data were performed. Tumor progression was defined as volumetric growth of 15% or greater over the imaging interval. Primary outcomes analyzed included survival free of radiographic and clinical progression. Secondary outcomes included new or worsened cranial neuropathy. RESULTS A total of 85 patients were treated with Gamma Knife radiosurgery (GKRS) for JP at the authors’ institution over the last 27 years. Sixty patients had pretreatment and serial posttreatment contrast-enhanced MRI follow-up suitable for volumetric analysis. A total of 214 MR images were analyzed to segment tumor images in a slice-by-slice fashion to calculate integral tumor volume. The median follow-up duration was 66 months (range 7–202 months). At 5 years the tumor progression-free survival rate was 98%. Three tumors exhibited progression more than 10 years after GKRS. Estimated survival free of radiographic progression rates (95% confidence interval [CI]; n = number still at risk) at 5, 10, and 15 years following radiosurgery were 98% (95% CI 94%–100%; n = 34), 94% (95% CI 85%–100%; n = 16), and 74% (95% CI 56%–98%; n = 6), respectively. One patient with tumor progression required treatment intervention using external beam radiation therapy, constituting the only case of clinical progression. Two patients (3%) without preexisting lower cranial nerve dysfunction developed new ipsilateral vocal fold paralysis following radiosurgery. CONCLUSIONS SRS achieves excellent long-term tumor control for JP without a high risk for new or worsened cranial neuropathy when used in primary, combined modality, or recurrent settings. Long-term follow-up is critical due to the potential for late radiographic progression (i.e., more than 10 years after SRS). As none of the patients with late progression have required salvage therapy, the clinical implications of this degree of tumor growth have yet to be determined.

Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44%, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68+ macrophages to S100+ macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80%). CD68+ cells were present at significantly higher concentrations in tumors that progressed (p = 0.03). Higher macrophage density was significantly associated with both tumor progression (p = 0.02) and unfavorable facial nerve function (p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint (p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.

Abstract FACIAL NERVE MONITORING Question 1 Does intraoperative facial nerve monitoring during vestibular schwannoma surgery lead to better long-term facial nerve function? Target Population This recommendation applies to adult patients undergoing vestibular schwannoma surgery regardless of tumor characteristics. Recommendation Level 3: It is recommended that intraoperative facial nerve monitoring be routinely utilized during vestibular schwannoma surgery to improve long-term facial nerve function. Question 2 Can intraoperative facial nerve monitoring be used to accurately predict favorable long-term facial nerve function after vestibular schwannoma surgery? Target Population This recommendation applies to adult patients undergoing vestibular schwannoma surgery. Recommendation Level 3: Intraoperative facial nerve can be used to accurately predict favorable long-term facial nerve function after vestibular schwannoma surgery. Specifically, the presence of favorable testing reliably portends a good long-term facial nerve outcome. However, the absence of favorable testing in the setting of an anatomically intact facial nerve does not reliably predict poor long-term function and therefore cannot be used to direct decision-making regarding the need for early reinnervation procedures. Question 3 Does an anatomically intact facial nerve with poor electromyogram (EMG) electrical responses during intraoperative testing reliably predict poor long-term facial nerve function? Target Population This recommendation applies to adult patients undergoing vestibular schwannoma surgery. Recommendation Level 3: Poor intraoperative EMG electrical response of the facial nerve should not be used as a reliable predictor of poor long-term facial nerve function. COCHLEAR NERVE MONITORING Question 4 Should intraoperative eighth cranial nerve monitoring be used during vestibular schwannoma surgery? Target Population This recommendation applies to adult patients undergoing vestibular schwannoma surgery with measurable preoperative hearing levels and tumors smaller than 1.5 cm. Recommendation Level 3: Intraoperative eighth cranial nerve monitoring should be used during vestibular schwannoma surgery when hearing preservation is attempted. Question 5 Is direct monitoring of the eighth cranial nerve superior to the use of far-field auditory brain stem responses? Target Population This recommendation applies to adult patients undergoing vestibular schwannoma surgery with measurable preoperative hearing levels and tumors smaller than 1.5 cm. Recommendation Level 3: There is insufficient evidence to make a definitive recommendation. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-manage-ment-patients-vestibular-schwannoma/chapter_4.

Abstract Please see the full-text version of this guideline (https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_3) for the target population of each recommendation listed below. STEREOTACTIC RADIOSURGERY Question 1 What is the overall probability of maintaining serviceable hearing following stereotactic radiosurgery utilizing modern dose planning, at 2, 5, and 10 yr following treatment? Recommendation Level 3 : Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled that there is moderately high probability (>50%-75%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 2 Among patients with AAO-HNS (American Academy of Otolaryngology-Head and Neck Surgery hearing classification) class A or GR (Gardner-Robertson hearing classification) grade I hearing at baseline, what is the overall probability of maintaining serviceable hearing following stereotactic radiosurgery, utilizing modern dose planning, at 2, 5, and 10 yr following treatment? Recommendation Level 3 : Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled that there is a high probability (>75%-100%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 3 What patient- and tumor-related factors influence progression to nonserviceable hearing following stereotactic radiosurgery using ≤13 Gy to the tumor margin? Recommendation Level 3: Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled regarding the probability of successful hearing preservation based on the following prognostic data: the most consistent prognostic features associated with maintenance of serviceable hearing are good preoperative word recognition and/or pure tone thresholds with variable cut-points reported, smaller tumor size, marginal tumor dose ≤12 Gy, and cochlear dose ≤4 Gy. Age and sex are not strong predictors of hearing preservation outcome. MICROSURGERY Question 4 What is the overall probability of maintaining serviceable hearing following microsurgical resection of small to medium-sized sporadic vestibular schwannomas early after surgery, at 2, 5, and 10 yr following treatment? Recommendation Level 3 : Individuals who meet these criteria and are considering microsurgical resection should be counseled that there is a moderately low probability (>25%-50%) of hearing preservation immediately following surgery, moderately low probability (>25%-50%) of hearing preservation at 2 yr, moderately low probability (>25%-50%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 5 Among patients with AAO-HNS class A or GR grade I hearing at baseline, what is the overall probability of maintaining serviceable hearing following microsurgical resection of small to medium-sized sporadic vestibular schwannomas early after surgery, at 2, 5, and 10 yr following treatment? Recommendation Level 3: Individuals who meet these criteria and are considering microsurgical resection should be counseled that there is a moderately high probability (>50%-75%) of hearing preservation immediately following surgery, moderately high probability (>50%-75%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 6 What patient- and tumor-related factors influence progression to nonserviceable hearing following microsurgical resection of small to medium-sized sporadic vestibular schwannomas? Recommendation Level 3: Individuals who meet these criteria and are considering microsurgical resection should be counseled regarding the probability of successful hearing preservation based on the following prognostic data: the most consistent prognostic features associated with maintenance of serviceable hearing are good preoperative word recognition and/or pure tone thresholds with variable cut-points reported, smaller tumor size commonly less than 1 cm, and presence of a distal internal auditory canal cerebrospinal fluid fundal cap. Age and sex are not strong predictors of hearing preservation outcome. CONSERVATIVE OBSERVATION Question 7 What is the overall probability of maintaining serviceable hearing with conservative observation of vestibular schwannomas at 2, 5, and 10 yr following diagnosis? Recommendation Level 3: Individuals who meet these criteria and are considering observation should be counseled that there is a high probability (>75%-100%) of hearing preservation at 2 yr, moderately high probability (>50%-75%) of hearing preservation at 5 yr, and moderately low probability (>25%-50%) of hearing preservation at 10 yr. Question 8 Among patients with AAO-HNS class A or GR grade I hearing at baseline, what is the overall probability of maintaining serviceable hearing with conservative observation at 2 and 5 yr following diagnosis? Recommendation Level 3: Individuals who meet these criteria and are considering stereotactic radiosurgery should be counseled that there is a high probability (>75%-100%) of hearing preservation at 2 yr, and moderately high probability (>50%-75%) of hearing preservation at 5 yr. Insufficient data were available to determine the probability of hearing preservation at 10 yr for this population subset. Question 9 What patient and tumor-related factors influence progression to nonserviceable hearing during conservative observation? Recommendation Level 3: Individuals who meet these criteria and are considering observation should be counseled regarding probability of successful hearing preservation based on the following prognostic data: the most consistent prognostic features associated with maintenance of serviceable hearing are good preoperative word recognition and/or pure tone thresholds with variable cut-points reported, as well as nongrowth of the tumor. Tumor size at the time of diagnosis, age, and sex do not predict future development of nonserviceable hearing during observation. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-manage-ment-patients-vestibular-schwannoma/chapter_3.

Abstract QUESTION 1 What is the expected diagnostic yield for vestibular schwannomas when using a magnetic resonance imaging (MRI) to evaluate patients with previously published definitions of asymmetric sensorineural hearing loss? TARGET POPULATION These recommendations apply to adults with an asymmetric sensorineural hearing loss on audiometric testing. RECOMMENDATION Level 3: On the basis of an audiogram, it is recommended that MRI screening on patients with ≥10 decibels (dB) of interaural difference at 2 or more contiguous frequencies or ≥15 dB at 1 frequency be pursued to minimize the incidence of undiagnosed vestibular schwannomas. However, selectively screening patients with ≥15 dB of interaural difference at 3000 Hz alone may minimize the incidence of MRIs performed that do not diagnose a vestibular schwannoma. QUESTION 2 What is the expected diagnostic yield for vestibular schwannomas when using an MRI to evaluate patients with asymmetric tinnitus, as defined as either purely unilateral tinnitus or bilateral tinnitus with subjective asymmetry? TARGET POPULATION These recommendations apply to adults with subjective complaints of asymmetric tinnitus. RECOMMENDATION Level 3: It is recommended that MRI be used to evaluate patients with asymmetric tinnitus. However, this practice is low yielding in terms of vestibular schwannoma diagnosis (<1%). QUESTION 3 What is the expected diagnostic yield for vestibular schwannomas when using an MRI to evaluate patients with a sudden sensorineural hearing loss? TARGET POPULATION These recommendations apply to adults with a verified sudden sensorineural hearing loss on an audiogram. RECOMMENDATION Level 3: It is recommended that MRI be used to evaluate patients with a sudden sensorineural hearing loss. However, this practice is low yielding in terms of vestibular schwannoma diagnosis (<3%). The full guideline can be found at: https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_2.

Objective: To present a single-institution experience and supportive systematic literature review examining outcomes after repeat microsurgery for recurrent vestibular schwannoma (VS) following previous gross total resection (GTR). Study Design: Retrospective review of prospectively maintained VS database. Systematic literature review. Setting: Tertiary referral center. Patients: Six proven VS recurrences after primary GTR, treated via repeat microsurgery. Intervention: Repeat microsurgery. Main Outcome Measures: Facial nerve function, extent-of-resection, time-to-repeat surgery, same versus alternate approach at repeat surgery (relative to primary operation). Results: GTR was achieved in four (67%). House–Brackmann (HB) grade I–II facial nerve function was achieved in five (87%), including one that improved from preoperative HB grade V. An alternate surgical approach was chosen in four (67%). Systematic review identified four studies documenting 50 cases with patient-specific outcomes after repeat microsurgery for recurrent VS. Our cohort had significantly longer mean time-to-repeat surgery (117 vs. 64 months, p = 0.03), was significantly less likely to have HB III–VI function postrepeat (17% vs. 68%, p = 0.04), and was significantly less likely to undergo same approach surgery (33% vs. 90%, p = 0.0002); rates of GTR were nonsignificant (67% vs. 94%, p = 0.1). Conclusion: We report a six-patient series of microsurgery for recurrent VS after GTR, and the first systematic review of this rare and challenging entity. Anecdotally, our findings suggest that an alternate surgical approach may facilitate easier access to the tumor, with less scar encountered during the approach. Our results confirm that repeat microsurgery for recurrent VS is safe and effective, even for larger tumors not typically amenable to stereotactic radiosurgery.