Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Hypofractionated Gamma Knife radiosurgery (hfGKRS) is increasingly considered for treating large or near-critical structure meningiomas because of potential safety advantages. However, data on optimal fractionation and long-term outcomes remain limited. This study evaluated the longer-term tumor control and toxicity after hfGKRS for intracranial meningiomas at 2 large centers, supplemented by a systematic review and meta-analysis of existing literature. METHODS:The analysis included 34 patients (site 1 = 25, site 2 = 9, median age 62.6 years) with 40 tumors (median volume 11.2 cm3). 62% was low-grade (World Health Organization grade 0-1) and 38% was high-grade (World Health Organization grade 2-3). The most common fractionation schemes were 20 Gy in 5 fractions for low-grade and 21 Gy in 3 fractions for high-grade tumors. The mean follow-up was 28.8 months. RESULTS:Only 6 of 34 patients did not have any previous treatment including surgery and/or radiotherapy. 82% of patient patients had neurological deficits before stereotactic radiosurgery. The estimated rate of 5-year tumor progression for low-grade and high-grade tumors was 7.7% (95% CI 0.41%-30%) and 36% (95% CI 12%-62%). Symptoms improved in 12 patients (35%) and worsened in 6 patients (16%), with 1 case attributed to tumor progression and no significant visual deterioration in 16 tumors within 3 mm of the optic apparatus. There was no statistically significant association between fractionation (3 vs 5) scheme and tumor control (P = .07) or survival (P = .12). Karnofsky Performance Status performance was a significant predictor of death (HR 0.89, P = .012) and tumor progression (HR 0.93, P = .048). The combined meta-analysis revealed a 5-year tumor control rate of 91.6% for low-grade and 37.9% for high-grade meningiomas. CONCLUSION/CONCLUSIONS:hfGKRS demonstrates durable control and acceptable safety for low-grade intracranial meningiomas. High-grade tumors showed less favorable outcomes comparable with single-session Gamma Knife radiosurgery historical data. Further prospective data are needed to confirm these findings and optimize fractionation strategies.

OBJECTIVE:Bilateral cochlear implantation (CI) is not routinely recommended in patients of advanced age due to concerns regarding cost-effectiveness and the medical risks of multiple operations in this population. This study seeks to evaluate outcomes of bilateral CI in post-lingually deafened adults over 65 years old. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-five post-lingually deafened adults over 65 years at the time of second implantation (CI2) and 11 post-lingually deafened adults over 65 years at the time of simultaneous implantation. INTERVENTIONS/METHODS:Bilateral cochlear implantation. MAIN OUTCOME MEASURES/METHODS:Bilateral CNC word scores at 1 year postoperatively. RESULTS:Bilateral CNC scores were significantly improved compared with preoperative scores 1 year postoperatively in both sequentially implanted patients (d=9.2%, P<0.001) and simultaneously implanted patients (d=44%, P=0.028). No significant correlations were observed between changes in bilateral CNC word scores at 1 year and age at the time of CI1 (r=0.095, P=0.665), age at the time of CI2 (r=0.034, P=0.879), or length of time between implantations (r=0.164, P=0.453) in sequentially implanted patients, nor was age at implantation correlated with changes in bilateral CNC scores at 1 year in simultaneously implanted patients (r=0.548, P=0.452). Finally, bilateral CNC scores of sequentially and simultaneously implanted patients were not found to be different at 1 year (d=4.5%, P=0.8905). CONCLUSIONS:Patients older than 65 years who underwent both sequential and simultaneous bilateral cochlear implantation showed similar and significant improvements in speech perception scores compared with preoperative scores. These outcomes were not correlated with age at the time of implantation or time between implantations in the case of sequentially implanted patients. This suggests that significant benefit can be seen even with advanced age at the time of implantation and longer time between implantations.

OBJECTIVE:To better understand the distance relationship of the stapes to the round window, to assist in intraoperative round window identification. STUDY DESIGN/METHODS:Retrospective review of CT temporal bone imaging and multiplanar image reformat analysis. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Patients above 18 years of age who underwent cochlear implantation between January 2020 and April 2025 and had preoperative computed tomography (CT) imaging of the temporal bone. Patients were excluded if they had prior surgical procedures that could distort the stapes superstructure (eg, stapedectomy) or if image quality/resolution precluded adequate visualization of the stapes crus. INTERVENTION/METHODS:None. MAIN OUTCOME MEASURE/METHODS:Prediction accuracy of the stapes intercrural width to locate the level of the round window. RESULTS:There were 102 ears that were studied, including 51 (50%) left and 51 (50%) right ears. The average measured intercrural width was 2.1 mm (SD: 0.17 mm). The maximum intercrural distance was found to be 2.6 mm, and the minimum distance was 1.7 mm. In all 102 (100%) ears, the intercrural distance of the stapes accurately predicted the level of the RW on image analysis. CONCLUSION/CONCLUSIONS:The stapes intercrural width can be utilized as an accurate predictor of the round window level and is a simple and intuitive intraoperative tool surgeons can utilize to safely gain access to the cochlea.

PURPOSE/OBJECTIVE:This prospective, non-randomized phase II single-arm pilot trial aimed to explore favorable mid-treatment nodal response (FMNR) through CT imaging to guide de-escalated chemoradiation therapy (CRT) in patients with favorable risk, node-positive HPV-associated oropharyngeal cancer (OPC). MATERIALS AND METHODS/METHODS:. At week 4, CT imaging evaluated nodal response: ≥40% reduction warranted de-escalation to 60 Gy, while <40% reduction continued standard CRT. Primary endpoint was 2-year PFS from initiation of dose de-escalated CRT. Tissue tumor modified viral (TTMV) HPV DNA samples and DW-MRI were collected at baseline and week 4. MDADI questionnaires were collected at baseline, 1, 3, 6, 12, and 24 months. RESULTS:Of 39 patients, 26 had FMNR and underwent de-escalated treatment. 13 pts had slow mid-treatment nodal shrinkage and received standard dose. At a median follow-up of 47.4 months, the 2-year PFS was 92.1% (95% CI: 0.72-0.98) for the deescalated dose group and 92.3% for the standard dose patients (95% CI: 0.57-0.99), p=0.96. With a median survival follow up of 48.9 months (range: 16.7-77.8 months), there were no deaths or distant failures. FMNR was associated with rapid TTMV HPV DNA clearance, reduced TTMV HPV DNA flare, lower baseline and week 4 MRI diffusivity, and higher baseline and week 4 MRI diffusional kurtosis. No differences in acute or late maximum grade 3-4 toxicity by patient were noted. MDADI composite scores showed minimal clinical important difference (MCID) in the de-escalated group at 1-month post-treatment while the standard group had MCID up to 1-year post-treatment. No patients required feeding tube placement. CONCLUSIONS:De-escalated CRT using CT-based mid-treatment nodal response in favorable risk, node-positive HPV-associated OPC achieved excellent 2-year PFS and OS rates and represents a potential approach in better selecting patients for treatment de-escalation.

BACKGROUND:Inferring risk for malignant transformation (MT) in patients with lesions diagnosed as mild or moderate oral epithelial dysplasia (low-grade OED) remains challenging. We developed two models assessing the risk of progression to high-grade OED (severe dysplasia or carcinoma in situ) or OSCC in patients with low-grade OED lesions. METHODS:We included demographic, risk habit and clinical data from participants with low-grade OED lesions enrolled in the BC Oral Cancer Prevention Program's Oral Cancer Prediction Longitudinal study. Cox proportional hazard models were fit to estimate the effects of anatomic site and toluidine blue findings and adjusted for confounders, as both are associated with MT in the literature but without a North American-specific cohort analysis. Our primary model included both variables of interest. A secondary model included only anatomic site since toluidine blue is not in widespread use. RESULTS:Five hundred and thirty-four participants with 605 lesions met final inclusion criteria, with 339 mild and 266 moderate OED at baseline. In the primary model, lesions at a high-risk anatomic site or with positive toluidine blue staining were associated with a 2.6 and 2.4-fold increased risk of progression, respectively. In the second model that did not incorporate toluidine blue, high-risk anatomic site remained a highly associated risk factor (2.7-fold increased risk of progression). CONCLUSION/CONCLUSIONS:Lesion anatomic site is associated with higher risk of MT for the general practitioner, while a specialist with access to toluidine blue results can assume additional risk associated with positive staining. These models may inform decisions for surveillance and intervention for OED.

BACKGROUND AND OBJECTIVES/OBJECTIVE: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 cm3 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/CONCLUSIONS: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.

OBJECTIVE:The purpose of this study is to review the current literature on the effect of hypovitaminosis D on voice. STUDY DESIGN/METHODS:Narrative review. METHODS:The literature search from electronic databases included PubMed/MEDLINE, EMBASE, SCOPUS, and Google Scholar. Search terms included voice, voice quality, voice disorders, larynx, laryngology, acoustic analysis, vitamin D, calcitriol, cholecalciferol, vitamin D deficiency, and vitamin D insufficiency. All studies on patients with vitamin D deficiency, which included subjective and objective voice assessments, were reviewed. RESULTS:A total of 39 studies were retrieved. Only four studies met the above-mentioned inclusion criteria and hence were included in this review. The total number of subjects analyzed was 466. The subjective voice outcome measures used were the Voice Handicap Index-10 (VHI-10), self-reported phonatory symptoms, and the GRBAS scale. Objective voice outcome measures included fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, maximum phonation time, and dysphonia severity index. CONCLUSION/CONCLUSIONS:Vitamin D deficiency has no significant effect on laryngeal muscles. There was no statistically significant difference in VHI-10 score, self-reported dysphonia, perceptual voice evaluation scores, or any of the acoustic measures between those with or without vitamin D deficiency.

BACKGROUND/OBJECTIVES/OBJECTIVE:Vocal fold (VF) muscle atrophy, often associated with neuromuscular disorders and aging, can lead to voice-related disability. Myostatin is well-known to mediate skeletal muscle atrophy via Smad2/3 signaling, whereas TGF-β1, a potent inducer of Smad2/3 signaling, is upregulated following VF injury. However, the impact of Smad2/3 signaling on laryngeal muscles remains unclear. This study provides foundational insight regarding Smad2/3-dependent atrophic responses of VF skeletal muscle cells, to ultimately develop novel therapeutic strategies for VF muscle atrophy. STUDY DESIGN/METHODS:In vitro. METHODS:Myoblasts isolated from the rat thyroarytenoid muscle were differentiated into myotubes in myogenic differentiation medium ±500 ng/mL myostatin or 10 ng/mL TGF-β1, in the presence or absence of an ALK4/5 inhibitor or siRNA targeting Smad2 and Smad3. Myotube formation and activation of Smad2/3 (nuclear localization of Smad2/3) were assessed via immunofluorescence. Transcription related to myotube differentiation and Smad2/3 signaling was quantified by qRT-PCR. RESULTS:Both myostatin and TGF-β1 suppressed myogenic differentiation, increased Smad2/3 nuclear intensity, downregulated Myh2, and upregulated downstream targets of Smad2/3 (Ccn2 and Serpine1) and Fbox32, an atrophy-related gene. These effects were more pronounced with TGF-β1 than with myostatin and were reversed by inhibition of ALK4/5. Furthermore, Smad2/3 knockdown via siRNA promoted myogenic differentiation, further supporting the role of Smad2/3 signaling in the atrophic response in VF myoblasts. CONCLUSIONS:Smad2/3 signaling mediates differentiation of VF myoblasts and TGF-β1, a potent mediator of fibrosis, elicited a more pronounced atrophic response than myostatin. Smad2/3 may be an attractive therapeutic target for VF muscle atrophy. LEVEL OF EVIDENCE/METHODS:NA.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:This study assessed the vocal health of performers returning to full-time performance after the COVID-19 pandemic shutdown and investigated how differences in voice usage, exposure to voice care professionals, and vocal pathology before and during the pandemic contributed to variability in self-perceived and instrumental vocal outcome measures. STUDY DESIGN/METHODS:This was a prospective, case-control observational study conducted at a single outpatient site. METHODS:Twenty-two patients, 11 cases and 11 controls, were enrolled for the study. All participants were full-time singing professionals prior to the COVID-19 pandemic. Cases were recruited from patients presenting to a tertiary care voice center for vocal or pharyngeal complaints. Controls were healthy volunteers recruited from the general population of professional singers in the surrounding metropolitan area. All participants provided responses to the Voice Handicap Index-10, Evaluation of Ability to Sing Easily, and Laryngopharyngeal Measure of Perceived Sensation validated questionnaires as well as a study survey with questions regarding vocal use and history prior to and during the pandemic. All participants underwent instrumental acoustic and videostroboscopic voice evaluations. RESULTS:Cases had poorer outcome measures overall and were more likely to report their voices were worse at study enrollment when compared to their prepandemic perception (P = 0.027). Cases tended to be older and less likely to have pursued alternative employment during the pandemic that involved increased speaking voice use (27% vs 55%), but these differences were not statistically significant. CONCLUSIONS:There was a variable response among performers to the prolonged hiatus from performing during the COVID-19 pandemic. Those with poorer outcomes tended to be older and may have used their voice less during the pandemic. These findings are consistent with detraining periods in the exercise physiology literature and support the construct of treating vocal performers as vocal athletes.