Identification and Characterization of Circulating Tumor Cells in Men Who have Undergone Prostatectomy for Clinically Localized, High Risk Prostate Cancer.

PURPOSE: Approximately 15% of men with newly diagnosed prostate cancer have high risk features which increase the risk of recurrence and metastasis. Better predictive biomarkers could allow for earlier detection of biochemical recurrence and change surveillance and adjuvant treatment paradigms. Circulating tumor cells are thought to represent the earliest form of metastases. However, their role as biomarkers in men with high risk, localized prostate cancer is not well defined. MATERIALS AND METHODS: Two to 5 months after prostatectomy we obtained blood samples from 37 patients with high risk, localized prostate cancer, defined as stage T3a or higher, Gleason score 8 or greater, or prostate specific antigen 20 ng/ml or greater. Circulating tumor cells were enumerated using a commercial platform. Matched tumor and single circulating tumor cell sequencing was performed. RESULTS: Circulating tumor cells were detected in 30 of 37 samples (81.1%) with a median of 2.4 circulating tumor cells per ml (range 0 to 22.9). Patients with detectable circulating tumor cells showed a trend toward shorter recurrence time (p=0.12). All patients with biochemical recurrence had detectable circulating tumor cells. Androgen receptor over expression was detected in 7 of 37 patients (18.9%). Patients with biochemical recurrence had more circulating tumor cell copy number aberrations (p=0.027). Matched tumor tissue and single circulating tumor cell sequencing revealed heterogeneity. CONCLUSIONS: We noted a high incidence of circulating tumor cell detection after radical prostatectomy and shorter time to biochemical recurrence in men with a higher circulating tumor cell burden and more circulating tumor cell copy number aberrations. Genomic alterations consistent with established copy number aberrations in prostate cancer were detectable in circulating tumor cells but often discordant with cells analyzed in bulk from primary lesions. With further testing in appropriately powered cohorts early circulating tumor cell detection could be an informative biomarker to assist with adjuvant treatment decisions.

Forecasting Rural and Urban Otolaryngologists, Radiation Oncologists, and Oropharyngeal Carcinoma.

OBJECTIVE: To forecast oropharyngeal carcinoma (OPC) incidence with otolaryngologist and radiation oncologist numbers per population by rural and urban counties through 2030. METHODS: Incident OPC cases were abstracted from the Surveillance, Epidemiology, and End Results 19 database, and otolaryngologists and radiation oncologists from the Area Health Resources File by county from 2000 to 2018. Variables were analyzed by metropolitan counties with over 1,000,000 people (large metros), rural counties adjacent to a metro (rural adjacent), and rural counties not adjacent to a metro (rural not adjacent). Data were forecasted via an unobserved components model with regression slope comparisons. RESULTS: Per 100,000 population, forecasted OPC incidence increased from 2000 to 2030 (large metro: 3.6 to 10.6 cases; rural adjacent: 4.2 to 11.9; rural not adjacent: 4.3 to 10.1). Otolaryngologists remained stable for large metros (2.9 to 2.9) but declined in rural adjacent (0.7 to 0.2) and rural not adjacent (0.8 to 0.7). Radiation oncologists increased from 1.0 to 1.3 in large metros, while rural adjacent remained similar (0.2 to 0.2) and rural not adjacent increased (0.2 to 0.6). Compared to large metros, regression slope comparisons indicated similar forecasted OPC incidence for rural not adjacent (p = 0.58), but greater for rural adjacent (p < 0.001, r = 0.96). Otolaryngologists declined for rural regions (p < 0.001 and p < 0.001, r = -0.56, and r = -0.58 for rural adjacent and not adjacent, respectively). Radiation oncologists declined in rural adjacent (p < 0.001, r = -0.61), while increasing at a lesser rate for rural not adjacent (p = 0.002, r = 0.96). CONCLUSIONS: Rural OPC incidence disparities will grow while the relevant, rural health care workforce declines. LEVEL OF EVIDENCE: NA Laryngoscope, 134:136-142, 2024.

Outcomes of Near-Total and Subtotal Resection of Sporadic Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate tumor control and facial nerve outcomes after gross-total (GTR), near-total (NTR), and subtotal resection (STR) of sporadic vestibular schwannomas (VS). DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched in August 2021 through inception following PRISMA guidelines. REVIEW METHODS: English language articles reporting tumor control and facial nerve outcomes of adults (≥18 years) with NTR and STR of VS were evaluated. Study characteristics, demographics data, tumor characteristics, type of surgical intervention, and outcome measures on tumor control and facial nerve function were collected. Pooled relative risk (RR) estimates for tumor recurrence and facial nerve outcomes were calculated and stratified by extent of resection. RESULTS: From an initial search of 2504 articles, 48 studies were included in the analysis. When comparing 1108 patients who underwent NTR to 3349 patients with GTR, the pooled RR of recurrence in the NTR cohort was 2.94 (95% confidence interval [CI] 1.65-5.24, P = .0002). When comparing 1016 patients who underwent STR to 6171 patients with GTR, the pooled RR of recurrence in the STR cohort was 11.50 (95% CI 6.64-19.92, P < .0001). Estimates for risk of tumor regrowth for less-than-complete resection are presented. There was no elevated risk of adverse facial nerve outcome (defined as House-Brackmann grade III and above) in each category of extent of resection compared to GTR. CONCLUSION: Extent of resection predicts risk of tumor recurrence/regrowth following microsurgical resection. Favorable facial nerve outcome should be weighed against the increased risk of regrowth and the potential need for further treatment.

Team Consistency in Reducing Operative Time in Head and Neck Surgery with Microvascular Free Flap Reconstruction.

OBJECTIVE(S): To evaluate the impact of consistent surgical teams on procedure duration in head and neck free tissue transfer, and to evaluate the length of stay and readmission rates with consistent teams. METHODS: A retrospective chart review of head and neck microvascular reconstruction by a single surgeon between August 2017 and November 2021 was performed. Procedure duration, wound complications, length of stay, and 30-day readmissions were analyzed. One circulating nurse (CN) and surgical technologist (ST) were considered "consistent" due to their prior work with the primary surgeon. All others were considered "ad hoc." Teams were "Consistent CN + ST," "Consistent ST," "Consistent CN," or "Ad hoc." Procedure duration between groups was compared via analysis of variance. Multivariate linear regression was performed to predict procedure duration. RESULTS: A total of 135 patients were included. Age, sex, and American Society of Anesthesiologists status did not significantly differ across groups (p = 0.963; p = 0.467; p = 0.908, respectively). The mean procedure duration was 339.3 min and differed significantly across all groups (p = 0.006, Cohen d = 0.32). Compared to the Ad hoc group, consistent teams demonstrated significant reductions in mean procedure duration (Consistent CN + ST: 58.4 min, p = 0.001, Cohen d = 0.67; Consistent ST: 51.6 min, p = 0.013, Cohen d = 0.61; Consistent CN: 44.5 min, p = 0.031, Cohen d = 0.52). Controlling for other factors, the ad hoc team predicted increased procedure duration on multivariate analysis ( ß 57.38, 19.92-94.85, p < 0.003). Wound complications, length of stay, and readmission rates did not differ significantly across groups (p = 0.940; p = 0.174; p = 0.935, respectively). CONCLUSION: Consistent CN and ST improve operative efficiency in head and neck-free tissue transfer. Future studies may evaluate the impact of team consistency on complications, physician burnout, and health systems costs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2154-2159, 2023.

Interpretable Computer Vision to Detect and Classify Structural Laryngeal Lesions in Digital Flexible Laryngoscopic Images.

OBJECTIVE: To localize structural laryngeal lesions within digital flexible laryngoscopic images and to classify them as benign or suspicious for malignancy using state-of-the-art computer vision detection models. STUDY DESIGN: Cross-sectional diagnostic study SETTING: Tertiary care voice clinic METHODS: Digital stroboscopic videos, demographic and clinical data were collected from patients evaluated for a structural laryngeal lesion. Laryngoscopic images were extracted from videos and manually labeled with bounding boxes encompassing the lesion. Four detection models were employed to simultaneously localize and classify structural laryngeal lesions in laryngoscopic images. Classification accuracy, intersection over union (IoU) and mean average precision (mAP) were evaluated as measures of classification, localization, and overall performance, respectively. RESULTS: In total, 8,172 images from 147 patients were included in the laryngeal image dataset. Classification accuracy was 88.5 for individual laryngeal images and increased to 92.0 when all images belonging to the same sequence (video) were considered. Mean average precision across all four detection models was 50.1 using an IoU threshold of 0.5 to determine successful localization. CONCLUSION: Results of this study showed that deep neural network-based detection models trained using a labeled dataset of digital laryngeal images have the potential to classify structural laryngeal lesions as benign or suspicious for malignancy and to localize them within an image. This approach provides valuable insight into which part of the image was used by the model to determine a diagnosis, allowing clinicians to independently evaluate models' predictions.

Pilot randomized, controlled, preoperative intervention for nutrition trial in head and neck cancer.

BACKGROUND: Several prospective studies report improved outcomes with pretreatment nutrition interventions prior to radiation therapy for head and neck cancer (HNC), but none have assessed similar interventions before surgery for HNC. METHODS: POINT, a pilot randomized controlled trial, was conducted to evaluate a multimodal nutrition intervention. Patients undergoing primary surgery with free flap reconstruction for HNC were randomly assigned to the control arm or a preoperative multimodal nutrition intervention. RESULTS: POINT included 49 patients. Nutrition risk scores did not change significantly for either the intervention or control group. Control patients had a significant decrease in body weight in the preoperative period (p < 0.001). Conversely, weight among intervention patients did not significantly decrease (p = 0.680). The intervention mitigated weight loss in patients with dysphagia (p = 0.001). CONCLUSIONS: Preoperative nutrition optimization shows potential to reduce weight loss normally experienced by patients with head and neck cancer prior to surgical extirpation, especially among those with subjective dysphagia.

Assessing the Risk of Adjuvant Radiotherapy Initiation Delays With Social Support Surveys.

OBJECTIVE: In patients with head and neck squamous cell carcinoma (HNSCC), initiating postoperative radiotherapy (PORT) greater than 42 days after surgery is associated with a higher risk of poor survival outcomes. Social support has been shown to modulate behaviors related to care-seeking and treatment adherence. In this study, we sought to determine the relationship between social support metrics and PORT delays. STUDY DESIGN: Prospective cohort study. SETTING: Single tertiary medical center. METHODS: Patients with HNSCC who underwent primary surgical excision requiring PORT were prospectively enrolled. Patient-perceived social support metrics were assessed using the Medical Outcomes Study Social Support Survey (MOS-SSS) at initial presurgical evaluation. Associations with PORT delays were evaluated via univariable and multivariable logistic regression analysis. RESULTS: A total of 111 patients met the inclusion criteria for the study. An additional 28 patients were recommended to receive PORT but did not initiate treatment and were included for secondary analysis. All four subscales of the MOS-SSS (positive social interaction, affectionate support, tangible support, and emotional/informational support) were significantly associated with PORT initiation delays on univariable analysis. On multivariable analysis, the overall MOS-SSS score (odds ratio [OR] 2.08, 1.15-4.35, p = .028) was significantly associated with PORT initiation delays. On secondary analysis, lower tangible support was associated with a lack of PORT initiation (OR 1.63, 1.05-2.54, p = .028). CONCLUSION: Social support metrics were significantly associated with PORT delays, which may help promote tighter scheduling and closer monitoring of high-risk patients.

Association of Social-Ecological Factors With Delay in Time to Initiation of Postoperative Radiation Therapy: A Prospective Cohort Study.

Importance: Timely initiation of postoperative radiation therapy (PORT) is associated with reduced recurrence rates and improved overall survival in patients with head and neck squamous cell carcinoma (HNSCC). Measurement of the association of social-ecological variables with PORT delays is lacking. Objective: To assess individual and community-level factors associated with PORT delay among patients with HNSCC. Design, Setting, and Participants: This prospective cohort study carried out between September 2018 and June 2022 included adults with untreated HNSCC who were enrolled in a prospective registry at a single academic tertiary medical center. Demographic information and validated self-reported measures of health literacy were obtained at baseline visits. Clinical data were recorded, and participant addresses were used to calculate the area deprivation index (ADI), a measure of community-level social vulnerability. Participants receiving primary surgery and PORT were analyzed. Univariable and multivariable regression analysis was performed to identify risk factors for PORT delays. Exposures: Surgical treatment and PORT. Main Outcomes and Measures: The primary outcome was PORT initiation delay (>42 days from surgery). Risk of PORT initiation delay was evaluated using individual-level (demographic, health literacy, and clinical data) and community-level information (ADI and rural-urban continuum codes). Results: Of 171 patients, 104 patients (60.8%) had PORT delays. Mean (SD) age of participants was 61.0 (11.2) years, 161 were White (94.2%), and 105 were men (61.4%). Insurance was employer-based or public among 65 (38.5%) and 75 (44.4%) participants, respectively. Mean (SD) ADI (national percentile) was 60.2 (24.4), and 71 (41.8%) resided in rural communities. Tumor sites were most commonly oral cavity (123 [71.9%]), with 108 (63.5%) classified as stage 4 at presentation. On multivariable analysis, a model incorporating individual-level factors with health literacy in addition to community-level factors was most predictive of PORT delay (AOC= 0.78; R2, 0.18). Conclusions and Relevance: This cohort study provides a more comprehensive assessment of predictors of PORT delays that include health literacy and community-level measures. Predictive models that incorporate multilevel measures outperform models with individual-level factors alone and may guide precise interventions to decrease PORT delay for at-risk patients with HNSCC.

Adjuvant radiotherapy mitigates impact of perineural invasion on oncologic outcomes in early-stage oral cavity squamous cell carcinoma. A multi-institutional analysis of 557 patients.

OBJECTIVES: Understand the prognostic impact of perineural invasion (PNI) in early-stage oral cavity squamous cell carcinoma (OCSCC). Assess the influence of adjuvant radiotherapy on outcomes of patients with PNI-positive early-stage OCSCC. MATERIALS AND METHODS: Retrospective seven-institution cohort study including patients with pathologic T1-2 N0-1 OCSCC who underwent primary surgery with negative margins. Outcomes included disease-free survival (DFS) and locoregional control (LRC). Cox proportional hazards models were used to evaluate oncologic outcomes. Interaction terms were introduced to assess relationships between PNI and adjuvant radiotherapy. RESULTS: Among 557 patients (mean (SD) age 61.0 (13.9), 47.2% female, 66.6% pathologic T1, 93.5% pathologic N0), 93 had PNI-positive tumors, among which 87.1% underwent neck dissection and 39.6% received radiotherapy. On multivariable analysis, PNI was associated with lower DFS and LRC. Adjuvant radiotherapy was not associated with improved outcomes on multivariable analysis of the entire cohort. However, among patients with PNI-positive tumors, adjuvant radiotherapy significantly decreased hazard for DFS. CONCLUSION: Among patients with low-risk, early-stage OCSCC, PNI was associated with worse DFS and LRC. In patients with PNI-positive tumors, adjuvant radiotherapy lowered hazard for DFS on multivariable analysis. These data support using adjuvant radiotherapy for patients with early-stage OCSCC with PNI.

(Even Off-Label) Cochlear Implantation in Single-Sided Deafness and Asymmetric Hearing Loss Results in Measurable Objective and Subjective Benefit.

OBJECTIVE: To quantify objective and subjective outcomes in cochlear implant (CI) recipients with asymmetric hearing loss, including single-sided deafness (SSD) whose candidacy was determined on an ear-specific basis when word recognition was 50% or less. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. BACKGROUND: The effectiveness of CI in cases of SSD and asymmetric hearing loss (AHL) has been described in terms of tinnitus suppression, improved speech recognition in quiet and noise, enhanced localization ability, and improved quality of life. However, CI is not yet routinely offered as a top option or standard of care for these individuals. Recent Food and Drug Administration (FDA) labeling limits aided word recognition in the ear to be implanted to only 5% in cases of AHL/SSD, which is significantly poorer than 40 to 50%, which is often referenced in cases of bilateral hearing loss. Anecdotal experience suggests that patients with much better preoperative word recognition than 5% can benefit from CI. METHODS: We conducted a retrospective chart review of all adult CI candidates, with one ear exhibiting consonant-nucleus-consonant (CNC) word recognition scores at least 50% and one ear not meeting CI candidacy (i.e., CNC word recognition >50%). Outcome variables of interest included word and sentence recognition and subjective handicap questionnaires (hearing, tinnitus, dizziness) and the Speech Spatial Qualities questionnaire. RESULTS: Statistically and clinically significant improvement in speech understanding (word, sentence, sentence in noise) was noted for both the SSD and AHL groups in the implanted ear. There were statistically and clinically significant subjective improvements noted for both groups on the Hearing Handicap Inventory, the Tinnitus Handicap Inventory, and the Speech Spatial Qualities questionnaire by 1 month after activation. There were no significant differences between the AHL and SSD groups on either objective or subjective measures of the implanted ear. Individual word understanding improved for the majority of recipients across both groups and is not dependent on meeting the FDA criteria of less than 5%. CONCLUSIONS: Cochlear implantation is a viable option with measurable objective and perceived benefits for recipients with preoperative aided CNC word scores exceeding current FDA labeling. There is no significant difference between the AHL and SSD groups, suggesting that candidacy and outcome expectations should be set based on the ear to be implanted alone, without regard for the ability of the better hearing ear.

Hearing loss patterns in enlarged vestibular aqueduct syndrome: Do fluctuations have clinical significance?

OBJECTIVES: To reveal hearing loss patterns in patients with enlarged vestibular aqueduct (EVA) syndrome according to demographic and clinical characteristics. METHODS: A retrospective, longitudinal study design was utilized to identify patients with EVA. Ears of patients were categorized into one of four cohorts: progressive fluctuating, progressive non-fluctuating, stable fluctuating, and stable non-fluctuating patterns. Pairwise and group comparisons were performed with non-parametric tests to assess vestibular aqueduct (VA) morphology, clinical, and demographic variables between hearing loss pattern cohorts. Rates of hearing loss in the subgroups were determined utilizing a mixed linear effects model. RESULTS: 44 patients (25 female, 19 male, median diagnosis age: 8.06 years) met inclusion criteria. 16 individuals demonstrated unilateral EVA and 29 had bilateral EVA, resulting in 74 total ears with EVA. Amongst the four cohorts, differences in operculum widths amongst groups were statistically significant (p = 0.049) while VA midpoint widths were not (p = 0.522). Progressive hearing loss ears without fluctuations demonstrated a 3.20 dB per year (p < 0.001) progression while progressive hearing loss ears with fluctuations reported a rate of 3.52 dB loss per year (p < 0.001). CONCLUSION: Hearing fluctuations occur similarly in EVA patients with stable and progressive hearing loss. With the exception of increased rates of hearing loss progression for fluctuating progressive hearing loss patients, vestibular aqueduct morphology, demographic, and clinical characteristics commonly reported are likely not strong predictors for whether patients will or will not experience fluctuating patterns of hearing loss.

Measuring competitive exclusion in non-small cell lung cancer.

In this study, we experimentally measure the frequency-dependent interactions between a gefitinib-resistant non-small cell lung cancer population and its sensitive ancestor via the evolutionary game assay. We show that cost of resistance is insufficient to accurately predict competitive exclusion and that frequency-dependent growth rate measurements are required. Using frequency-dependent growth rate data, we then show that gefitinib treatment results in competitive exclusion of the ancestor, while the absence of treatment results in a likely, but not guaranteed, exclusion of the resistant strain. Then, using simulations, we demonstrate that incorporating ecological growth effects can influence the predicted extinction time. In addition, we show that higher drug concentrations may not lead to the optimal reduction in tumor burden. Together, these results highlight the potential importance of frequency-dependent growth rate data for understanding competing populations, both in the laboratory and as we translate adaptive therapy regimens to the clinic.

Olfactory, Auditory, and Vestibular Performance: Multisensory Impairment Is Significantly Associated With Incident Cognitive Impairment.

Background: Dysfunction in the olfactory, auditory, and vestibular systems are commonly seen in aging and are associated with dementia. The impact of sensory loss(es) on cognition is not well understood. Our aim was to assess the relationships between performance on objective multisensory testing and quantify the impact of dysfunction on cognition. Methods: Patients presenting with subjective hearing loss presenting to a tertiary care otologic/audiologic clinic were identified and underwent multisensory testing using the Affordable, Rapid Olfactory Measurement Array (AROMA), pure tone audiometric evaluations, and the Timed "Up and Go" test. Cognitive impairment (CI) was assessed via the Montreal Cognitive Assessment (MoCA) was also administered. Key Results: 180 patients were enrolled. Thirty one percentage (n = 57) screened positive for cognitive impairment. When evaluating single sensory impairments, we found that olfactory dysfunction, gait impairment, and sensorineural hearing loss were all statistically significantly (p < 0.05) associated with a higher risk of cognitive impairment (ORs 3.89, 3.49, and 2.78, respectively) for CI. Multisensory impairment was significantly associated with cognitive impairment. Subjects with dysfunction in all domains were at the highest risk for cognitive impairment (OR 15.7, p < 0.001) vs. those with impairment in 2 domains (OR 5.32, p < 0.001). Conclusion: Dysfunction of the olfactory, auditory, and vestibular systems is associated with a significantly increased risk of CI. The dramatically increased risk of CI with multisensory dysfunction in all three systems indicated that MSD may synergistically contribute to CI.

Sinus Surgery and Balloon Sinuplasty: What Do Patients Want to Know?

OBJECTIVE: Limited knowledge exists regarding the information patients seek online about sinus procedures. The goals of our study were to identify the most searched online queries regarding functional endoscopic sinus surgery (FESS) and balloon sinuplasty and evaluate the sources to which patients are directed. STUDY DESIGN: Observational. SETTING: Online Google Database. METHODS: Google data were analyzed using the search engine optimization tool Ahrefs. People Also Ask (PAA) questions (extracted from Google searches) helped identify questions for analysis of search query volume. Search results were categorized into specific topics, and the source (eg, academic vs medical practice) of the information was identified. The JAMA benchmark criteria were used to determine the quality of the online resource. RESULTS: The most searched term (average monthly queries) on Google was "sinus surgery" (13,190), followed by "balloon sinuplasty" (9212). For FESS and balloon sinuplasty, most questions focused on treatment of sinusitis (71.64% vs 79.19%) and preoperative inquiries about sinus issues (11.50% vs 11.35%). Answers to PAA questions for FESS were obtained from academic sources at a higher frequency compared to balloon sinuplasty (26.7% vs 10.3%, P = .016) but a lower frequency from medical practice websites (15.2% vs 29.3%, P = .042). The mean (SD) JAMA scores for FESS and balloon sinuplasty sources were 1.59 (1.46) and 1.40 (1.46), respectively. CONCLUSION: There is a high volume of online search queries regarding FESS and balloon sinuplasty. The quality of the sources could be improved by addressing authorship, attribution, disclosure, and currency. This information may help otolaryngologists better address patient queries.

Identifying Olfactory Phenotypes to Differentiate Between COVID-19 Olfactory Dysfunction and Sinonasal Inflammatory Disease.

The objective of this study was to identify specific olfactory phenotypes-patterns of olfactory performance-across distinct cohorts with or without olfactory dysfunction (OD). Adult patients underwent testing via a novel olfactory testing methodology in 1 of 4 groups based on health status: sinonasal inflammatory condition (chronic rhinosinusitis or allergic rhinitis), ≥4 weeks of self-reported OD after resolved COVID-19 infection, Alzheimer's disease, and healthy control. Participants' scores for each scent were normalized on a scale of 0 to 1 relative to their worst and best scores. Agglomerative hierarchal cluster analysis was performed on normalized data for the COVID-19 and sinonasal cohorts. Resulting clusters from the penultimate merger revealed a sensitivity of 81% and specificity of 63% for the detection of patients with COVID-19. These results support that there are olfactory phenotypes that may discriminate COVID-19 OD from sinonasal inflammatory disease. These phenotypes will likely become increasingly leveraged in the workup and treatment of patients with OD.

Predictive Modeling and Risk Stratification of Patients With Enlarged Vestibular Aqueduct.

OBJECTIVES/HYPOTHESIS: To investigate patient-specific characteristics that independently predict for progressive hearing loss in patients with enlarged vestibular aqueduct (EVA). Utilize multivariable predictive models to identify subgroups of patients with significantly different progression risks. STUDY DESIGN: Retrospective analysis of patients evaluated at an academic tertiary care center. Cohort included 74 ears of patients with a diagnosis of EVA as defined by the Cincinnati criteria. METHODS: Hearing trajectories were characterized, and a Kaplan-Meier estimator was utilized to determine progressive phenotype probabilities across the first 10 years after diagnosis. Cox proportional hazard regression was used to identify patient characteristics that independently altered this probability. Stratified risk groups were delineated from generated nomogram scores. RESULTS: Male gender was associated with a 4.53 hazard ratio for progressive hearing loss (95% confidence interval [CI], 2.53 to 12.59). Each millimeter increase in operculum size was independently associated with an 80.40% increase in expected hazard (95% CI, 40.18 to 120.62). Each dB increase in air pure tone average at time of diagnosis decreased expected hazard by 1.59% (95% CI, -3.02 to -0.17). The presence of incomplete partition type II was associated with a 2.44 hazard ratio (95% CI, 1.04 to 5.72). Risk groups stratified by median nomogram score evidenced the discriminative ability of our model with the progression probability in the high-risk group being six times higher at 1 year, nearly five times greater at 3 years, and three times greater at 9 years. CONCLUSIONS: EVA patient characteristics can be used to predict hearing loss probability with a high degree of accuracy (C-index of 0.79). This can help clinicians make more proactive management decisions by identifying patients at high risk for hearing loss. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1439-1445, 2022.

Development and Validation of Machine Learning Models for Predicting Occult Nodal Metastasis in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Importance: Given that early-stage oral cavity squamous cell carcinoma (OCSCC) has a high propensity for subclinical nodal metastasis, elective neck dissection has become standard practice for many patients with clinically negative nodes. Unfortunately, for most patients without regional metastasis, this risk-averse treatment paradigm results in unnecessary morbidity. Objectives: To develop and validate predictive models of occult nodal metastasis from clinicopathological variables that were available after surgical extirpation of the primary tumor and to compare predictive performance against depth of invasion (DOI), the currently accepted standard. Design, Setting, and Participants: This diagnostic modeling study collected clinicopathological variables retrospectively from 7 tertiary care academic medical centers across the US. Participants included adult patients with early-stage OCSCC without nodal involvement who underwent primary surgical extirpation with or without upfront elective neck dissection. These patients were initially evaluated between January 1, 2000, and December 31, 2019. Exposures: Largest tumor dimension, tumor thickness, DOI, margin status, lymphovascular invasion, perineural invasion, muscle invasion, submucosal invasion, dysplasia, histological grade, anatomical subsite, age, sex, smoking history, race and ethnicity, and body mass index (calculated as weight in kilograms divided by height in meters squared). Main Outcomes and Measures: Occult nodal metastasis identified either at the time of elective neck dissection or regional recurrence within 2 years of initial surgery. Results: Of the 634 included patients (mean [SD] age, 61.2 [13.6] years; 344 men [54.3%]), 114 (18.0%) had occult nodal metastasis. Patients with occult nodal metastasis had a higher frequency of lymphovascular invasion (26.3% vs 8.1%; P < .001), perineural invasion (40.4% vs 18.5%; P < .001), and margin involvement by invasive tumor (12.3% vs 6.3%; P = .046) compared with those without pathological lymph node metastasis. In addition, patients with vs those without occult nodal metastasis had a higher frequency of poorly differentiated primary tumor (20.2% vs 6.2%; P < .001) and greater DOI (7.0 vs 5.4 mm; P < .001). A predictive model that was built with XGBoost architecture outperformed the commonly used DOI threshold of 4 mm, achieving an area under the curve of 0.84 (95% CI, 0.80-0.88) vs 0.62 (95% CI, 0.57-0.67) with DOI. This model had a sensitivity of 91.7%, specificity of 72.6%, positive predictive value of 39.3%, and negative predictive value of 97.8%. Conclusions and Relevance: Results of this study showed that machine learning models that were developed from multi-institutional clinicopathological data have the potential to not only reduce the number of pathologically node-negative neck dissections but also accurately identify patients with early OCSCC who are at highest risk for nodal metastases.

Assessing Prognostic Value of Quantitative Neck Dissection Quality Measures in Patients With Clinically Node-Negative Oral Cavity Squamous Cell Carcinoma.

Importance: In clinically localized (T1-2) oral cavity squamous cell carcinoma (OCSCC), regional lymph node metastasis is associated with a poor prognosis. Given the high propensity of subclinical nodal disease in these patients, upfront elective neck dissections (END) for patients with clinically node-negative disease are common and associated with better outcomes. Unfortunately, even with this risk-adverse treatment paradigm, disease recurrence still occurs, and our understanding of the factors that modulate this risk and alter survival have yet to be fully elucidated. Objective: To investigate the prognostic value of lymph node yield (LNY), lymph node ratio (LNR), and weighted LNR (wLNR) in patients with clinically node-negative T1-2 OCSCC. Design, Setting, and Participants: In this cohort study, data were collected retrospectively from 7 tertiary care academic medical centers. Overall, 523 patients with cT1-2N0 OCSCC who underwent elective neck dissections after primary surgical extirpation were identified. Exposures: Lymph node yield was defined as the number of lymph nodes recovered from elective neck dissection. Lymph node ratio was defined as the ratio of positive nodes against total LNY. Weighted LNR incorporated information from both LNY and LNR into a single continuous metric. Main Outcomes and Measures: Locoregional control (LRC) and disease-free survival (DFS) were both evaluated using nonparametric Kaplan-Meier estimators and semiparametric Cox regression. Results: On multivariable analysis, LNY less than or equal to 18 lymph nodes was found to be significantly associated with decreased LRC (aHR, 1.53; 95% CI, 1.04-2.24) and DFS (aHR, 1.46; 95% CI, 1.12-1.92) in patients with pN0 disease, but not those with pN-positive disease. Importantly, patients with pN0 disease with LNY less than or equal to 18 and those with pN1 diseasehad nearly identical 5-year LRC (69.7% vs 71.4%) and DFS (58.2% vs 55.7%). For patients with pN-positive disease, LNR greater than 0.06 was significantly associated with decreased LRC (aHR, 2.66; 95% CI, 1.28-5.55) and DFS (aHR, 1.65; 95% CI, 1.07-2.53). Overall, wLNR was a robust prognostic variable across all patients with cN0 disease, regardless of pathologic nodal status. Risk stratification via wLNR thresholds demonstrated greater optimism-corrected concordance compared with American Joint Committee on Cancer (AJCC) 8th edition nodal staging for both LRC (0.61 vs 0.57) and DFS (0.61 vs 0.58). Conclusions and Relevance: Movement toward more robust metrics that incorporate quantitative measures of neck dissection quality and regional disease burden, such as wLNR, could greatly augment prognostication in cT1-2N0 OCSCC by providing more reliable and accurate risk estimations.

UV decontamination of personal protective equipment with idle laboratory biosafety cabinets during the COVID-19 pandemic.

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm-2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 µWcm-2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.