Faculty Bibliography

Objectives To characterize treatment and hearing outcomes for cerebellopontine angle (CPA) meningiomas with inherent risks of hearing loss and identify predictors of hearing loss for surgically treated lesions. Design Retrospective chart review. Setting Tertiary care medical center. Participants Adult patients with CPA meningiomas impinging upon cranial nerve VIII and/or pretreatment hearing loss managed with microsurgery or stereotactic radiosurgery (SRS) with Gamma Knife at our center between 2012 and 2023. Main Outcome Measures Hearing preservation rate was determined from analysis of patients with pretreatment serviceable hearing for whom hearing-preserving treatment was attempted. Surgical patients were further analyzed using multivariable Cox proportional hazards regression models to identify factors predictive of postoperative hearing loss. Results We identified 80 patients with CPA meningiomas meeting inclusion criteria who were managed with either microsurgery (43, 54%) or radiosurgery (37, 46%). Following SRS, hearing was preserved in 88% of cases. Following microsurgery, hearing was preserved in 71% of patients-all patients who lost hearing had tumors involving the internal auditory canal (IAC). Among surgical patients only, multivariable analysis accounting for preoperative hearing, recurrence status, lesion size, and patient age, the preoperative imaging finding that the CPA meningioma surrounded the vestibulocochlear nerve was significantly associated with hearing loss (hazard ratio: 10.3, 95% confidence interval: 1.3-81.4, p = 0.02). Conclusion Most patients with meningiomas of the CPA can experience preservation of hearing, even when there is risk of hearing loss based on pretreatment evaluation. IAC invasion and surrounding of eighth nerve by tumor may portend poorer hearing outcomes in surgically managed patients.

The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.

BACKGROUND/UNASSIGNED:Patients with head and neck cancer (HNC) often experience high symptom burden leading to lower quality of life (QoL). OBJECTIVE/UNASSIGNED:This study aims to conceptually model optimal cutpoint by examining where total number of patient-reported symptoms exceeds patients' coping capacity, leading to a decline in QoL in patients with HNC. METHODS/UNASSIGNED:Secondary data analysis of 105 individuals with HNC enrolled in a clinical usefulness study of the NYU Electronic Patient Visit Assessment (ePVA)©, a digital patient-reported symptom measure. Patients completed ePVA and European Organization for Research and Treatment of Cancer (EORTC©) QLQ-C30 v3.0. The total number of patient-reported symptoms was the sum of symptoms as identified by the ePVA questionnaire. Analysis of variance (ANOVA) was used to define optimal cutpoint. RESULTS/UNASSIGNED:<.0001). CONCLUSIONS/UNASSIGNED:In HNC, defining optimal cutpoints in the total number of patient-reported symptoms is feasible. IMPLICATIONS FOR PRACTICE/UNASSIGNED:Cutpoints in the total number of patient-reported symptoms may identify patients experiencing a high symptom burden from HNC. FOUNDATIONAL/UNASSIGNED:Using optimal cutpoints of the total number of patient-reported symptoms may help effectively align clinical resources with patients' symptom burden.

In nature, animal vocalizations can provide crucial information about identity, including kinship and hierarchy. However, lab-based vocal behavior is typically studied during brief interactions between animals with no prior social relationship, and under environmental conditions with limited ethological relevance. Here, we address this gap by establishing long-term acoustic recordings from Mongolian gerbil families, a core social group that uses an array of sonic and ultrasonic vocalizations. Three separate gerbil families were transferred to an enlarged environment and continuous 20-day audio recordings were obtained. Using a variational autoencoder (VAE) to quantify 583,237 vocalizations, we show that gerbils exhibit a more elaborate vocal repertoire than has been previously reported and that vocal repertoire usage differs significantly by family. By performing gaussian mixture model clustering on the VAE latent space, we show that families preferentially use characteristic sets of vocal clusters and that these usage preferences remain stable over weeks. Furthermore, gerbils displayed family-specific transitions between vocal clusters. Since gerbils live naturally as extended families in complex underground burrows that are adjacent to other families, these results suggest the presence of a vocal dialect which could be exploited by animals to represent kinship. These findings position the Mongolian gerbil as a compelling animal model to study the neural basis of vocal communication and demonstrates the potential for using unsupervised machine learning with uninterrupted acoustic recordings to gain insights into naturalistic animal behavior.

OBJECTIVE:To investigate the impact of adjuvant radiotherapy in isolated locally advanced oral cavity cancers (pT3N0M0) without adverse features. METHODS:We selected all patients from the National Cancer Database (2004-2019) who underwent surgical treatment where the final pathology was T3N0M0 with negative margins. Demographics, details of treatment, and outcomes were abstracted. The impact of radiotherapy on survival was assessed with univariable, multivariable, and propensity score-matched analyses. RESULTS:We identified 571 patients in our survival cohort. Most were male (348, 60.9%), and median age was 65. Less than one-third (176, 30.8%) received adjuvant radiotherapy. The median length of follow-up was 29 months. Overall, adjuvant radiotherapy was associated with improved survival (87.2% vs. 77.7%, at 2 years, p < 0.01). On multivariable analysis controlling for age and comorbidities, this survival difference persisted (HR: 0.62, 95% CI: 0.43-0.90, p = 0.01). In a propensity score-matched population of 278 patients matched on age and comorbidities, adjuvant radiotherapy was still associated with longer survival (87.4% vs. 78.5%, p = 0.014). CONCLUSION/CONCLUSIONS:In our study, adjuvant radiotherapy was associated with improved survival in completely excised locally advanced oral cavity tumors (T3N0M0). However, a significant proportion of patients do not receive adjuvant radiotherapy. These findings highlight the need for continued efforts to promote guideline-recommended care. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 134:2236-2242, 2024.

BACKGROUND/UNASSIGNED:Microgenia resulting from congenital deficiency or aging can significantly affect the facial profile and render it less attractive. This study assessed the effectiveness of treatment with incobotulinumtoxinA (Inco) and calcium hydroxylapatite with integral lidocaine (CaHA[+]) for improving chin profile. METHODS/UNASSIGNED:Subjects with a hyperactive mentalis and at least moderate chin retrusion according to the Asian Chin Projection Scale (ACPS) were recruited. At Visit 1, subjects received Inco injection into the mentalis, followed by deep, pre-periosteal injections of CaHA(+) into the pogonion. The primary endpoint was an ACPS improvement of one point at one and six months. Photographs at baseline and each follow-up visit were rated by physicians using the Global Aesthetic Improvement Scale (GAIS). All subjects completed a satisfaction questionnaire. RESULTS/UNASSIGNED:Ten female subjects were recruited. Mean age was 42.5 years and all had moderate-to-severe chin retrusion at baseline (ACPS score ≥2). All subjects demonstrated at least a one-point improvement in ACPS compared with baseline at both the one-month and six-month posttreatment visits. Physician GAIS ratings of subject appearance confirmed that 100 percent of subjects experienced improved chin projection at each follow-up visit compared to baseline. All 10 subjects were pleased with their chin profile after treatment, with 90 percent noting that it was still "very much improved" at six months. CONCLUSION/UNASSIGNED:Based on our results, combined treatment with CaHA and Inco appears to be effective and well tolerated for improving the facial profile of subjects with chin retrusion. Treatment was associated with a high degree of patient satisfaction and was well tolerated.

Oral cancer is notoriously painful. Activation of protease-activated receptor 2 (PAR₂, encoded by F2RL1) by proteases in the cancer microenvironment is implicated in oral cancer pain. PAR₂ is a G protein-coupled receptor (GPCR) expressed on neurons and cells in the cancer microenvironment. Sustained signaling of PAR₂ from endosomes of neurons mediates sensitization and nociception. We focused on the differential contribution of PAR₂ on oral cancer cells and neurons to oral cancer pain and whether encapsulation of a PAR₂ inhibitor, AZ3451 in nanoparticles (NP) more effectively reverses PAR₂ activation. We report that F2RL1 was overexpressed in human oral cancers and cancer cell lines. Deletion of F2RL1 on cancer cells reduced cancer-associated mechanical allodynia. A third-generation polyamidoamine dendrimer, functionalized with cholesterol was self-assembled into NPs encapsulating AZ3451. NP encapsulated AZ3451 (PAMAM-Chol-AZ NPs) more effectively reversed activation of PAR₂ at the plasma membrane and early endosomes than free drug. The PAMAM-Chol-AZ NPs showed greater efficacy in reversing nociception than free drug, with respect to both level and duration, in three preclinical mouse models of oral cancer pain. The antinociceptive efficacy was confirmed with an operant orofacial assay. Genetic deletion of F2RL1 on cancer cells or F2rl1 on neurons each partially reversed mechanical cancer allodynia. The remaining nociception could be effectively reversed by PAMAM-Chol-AZ NPs. These findings suggest that PAR₂ on oral cancer cells and neurons contribute to oral cancer nociception and NPs loaded with a PAR₂ antagonist provide increased antinociception and improved oral function compared to free drug.

OBJECTIVES/UNASSIGNED:Acute post-thyroidectomy bilateral vocal cord paresis or paralysis (BVCP) is often managed with observation, botulinum toxin injection or tracheostomy. However, only a few cases discuss obstructive sleep apnea (OSA) in the context of BVCP with limited exploration of home sleep test (HST) and continuous positive airway pressure (CPAP) as post-operative assessment and management tools. This study suggests CPAP as a less invasive approach while awaiting vocal cord recovery. METHODS/UNASSIGNED:A retrospective chart review was conducted on 2 female patients who presented with dyspnea and sleep-disordered breathing (SDB) symptoms post-thyroidectomy. Both patients underwent laryngoscopy and HSTs, followed by CPAP prescription. RESULTS/UNASSIGNED:), aged 66 and 77 respectively, presented with post-surgery dyspnea and SDB symptoms. Laryngoscopy revealed left vocal cord paresis and right vocal cord paralysis in both cases. Although tracheostomy could provide definitive treatment, both cases were deferred for non-invasive options, which led to HST, confirming moderate OSA (PAT-derived apnea-hypopnea index (pAHI): 18/hour and 27.1/hour) leading to CPAP recommendation. In Case 2, 5 weeks of CPAP use resulted in dramatic improvements in her sleep quality, with continued benefits at 3-month follow-up. CONCLUSION/UNASSIGNED:These cases underscore the value of considering sleep studies and CPAP as adjunctive tools in acute post-thyroidectomy BVCP management while awaiting vocal motion recovery. This report also further supports that BVCP sufficiently narrows the glottic airway, predisposing patients to OSA.