Abel, Kathryn M. Van

ImportanceThere is a lack of reliable, patient-reported quality-of-life (QOL) instruments to address the multidimensional nature of patient-centered outcomes for patients undergoing parotidectomy. The Parotidectomy Quality of Life Index is a new 35-item validated patient-reported outcome instrument specific to recovery after parotidectomy.ObjectiveTo establish and validate a comprehensive English-language patient-reported QOL instrument specific to parotidectomy.Design, Setting, and ParticipantsThis survey study was conducted in 2 phases: first, in a single-institution cohort (October 12, 2021, to March 7, 2022), and second, as an anonymous web-based survey enrolled via printed promotional brochures and social media platforms (March 13 to July 31, 2023). Inclusion criteria were age at least 18 years and parotidectomy within the last year. For test-retest reliability, a subset of phase II participants volunteered to answer the survey a second time within 2 weeks. Data were analyzed from March 8, 2022, to November 3, 2023.Main Outcomes and MeasuresItem rankings from phase I participants were used to narrow the original 61-item survey down to 45 items in the phase II survey. To assess construct validity, an exploratory factor analysis was performed. Cronbach α and pairwise Pearson correlation coefficients were used to measure internal consistency, reliability, and redundancy. Test-retest reliability was evaluated using intraclass correlation coefficients.ResultsPhase I enrolled 38 individuals, of whom 30 completed the survey (15 women [60%]; 21 participants [84%] aged >40 years). Phase II enrolled 342 participants, of whom 317 completed the survey (305 women [89%]; 284 participants [83%] aged >40 years). A total of 42 items across 7 domains were selected based on exploratory factor analysis. After Cronbach α and pairwise correlation analysis, 33 items across 6 multi-item domains and 2 standalone items were incorporated into the final QOL instrument. Cronbach αs for each of the final 6 domains were at least 0.77, suggesting excellent internal validity. Pairwise correlations did not show strong correlations (ie, none ≥0.80), suggesting minimal redundancy between domains. Younger age was significantly associated with a lower global score. Participants with malignant tumors scored lower on 4 of the 6 multi-item domains. Test-retest reliability coefficients for the domains ranged from 0.82 to 0.93, indicating very good reproducibility over a 2-week interval.Conclusions and RelevanceThese findings suggest the Parotidectomy Quality of Life Index demonstrated excellent internal validity and test-retest reliability. With further external validation, this instrument may provide opportunity for quality improvement in clinical practice and has potential as a key patient-reported outcome in future parotidectomy clinical trials.

Abstract Purpose: Tumor-infiltrating lymphocytes are associated with a decreased risk of recurrence in human papillomavirus–associated oropharyngeal squamous cell carcinoma. The composition and spatial distribution of tumor-infiltrating lymphocytes and tumor-infiltrating immune cells are not well characterized. Experimental Design: Formalin-fixed, paraffin-embedded primary and lymph node (LN) tumor tissues from 10 progressors (cases) and 10 matched nonprogressors (controls) were interrogated by imaging mass cytometry. Immune, stromal, and tumor cells were quantified from selected regions of interest using machine learning. Nearest neighbors, cell–cell interactions, and niche analyses were performed. Results: In primary regions of interest, immune cell, lymphocyte, T cell, CD8+ T cell, and innate cell prevalence was significantly greater in controls. High prevalence of immune cells, lymphocytes, innate cells, and CD4+ T cells in primary tissues was significantly associated with increased time to event (TTE). Although primary and LN prevalence of T cells, CD4+ T cells, CD8+ T cells, macrophages, and tumor cells were significantly correlated, differences in LNs were neither significant nor associated with TTE. Average distances between T cells and the nearest B cells and between lymphocytes and the nearest tumor cells were decreased in control primary tissues. Interactions between B and T cells were less organized in primary tissues from cases. A niche predominantly comprising lymphocytes was associated with longer TTE. Conclusions: In human papillomavirus–associated oropharyngeal squamous cell carcinoma, immune cell subset prevalence in primary tumors differs with outcome and is associated with TTE. Interactions between B cells and both T-cell subsets are associated with longer TTE, underscoring the importance of active intratumoral immune responses in outcomes.

Abstract Objective Margin distance is a significant prognosticator in oral cavity cancer but its role in HPV‐related oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] remains unclear. Here, we investigate the impact of margin distance on locoregional recurrence in HPV(+)OPSCC. Study Design This is a retrospective cohort study of surgically treated HPV(+)OPSCC patients. Patients received either standard of care (at least 60 Gy with or without cisplatin) or de‐escalated adjuvant therapy (30‐36 Gy with concurrent docetaxel). Margin distance was measured in mm from the primary specimen or in combination with separately submitted margins. Kaplan‐Meier survival analysis with univariate and multivariable Cox regressions were conducted to determine the impact of margin distance on risk of local and locoregional recurrence. Setting Setting for this is 3 tertiary centers between January 2010 and February 2024. Results Among 1102 included patients, 33 (3.0%) had positive final margins. 374 patients had adequate margin distance data available. Margin distance was >3 mm in 73.4%, 1 to 3 mm in 24.5%, and <1 mm in 2.2% of patients. Positive final margins, pT4 disease, pN2 disease, and surgery alone as a treatment modality ( P < .02 for all) was associated with higher risk of 5‐year locoregional recurrence. Margin distance did not significantly impact risk of local or locoregional recurrence even after adjusting for de‐escalated adjuvant therapy ( P > .05). Conclusion Positive final margins after TORS without adjuvant radiotherapy for HPV(+)OPSCC carries a high risk of local recurrence. Margin distance does not appear to significantly impact risk of local or locoregional recurrence, even after de‐escalated adjuvant radiotherapy.

AbstractObjectiveThe extent of parotidectomy for benign tumors has de‐escalated in the United States. We aim to define modern benchmarks for operative time and hospital length of stay (LOS) in parotidectomy and identify risk factors that may prolong these benchmarks.Study DesignThis is a retrospective cross‐sectional study of all adults who underwent parotidectomy for a primary parotid neoplasm between January 2011 and December 2021 using the American College of Surgeons National Surgical Quality Improvement Program database.MethodsThe extent of parotidectomy was defined using Current Procedural Terminology codes. Prolonged operative time and LOS were defined as above the 75th percentile (longer than 194 minutes and more than 1 day, respectively). Multivariable logistic regression was used to identify patient and surgical risk factors that predict prolonged operative time or LOS.ResultsBenign parotidectomies are mostly performed as outpatient procedures in the United States (average LOS <1 day). Prolonged operative time was independently associated with malignant tumors versus benign tumors (adjusted odds ratio [aOR]: 2.7, 95% confidence interval [CI]: 2.4‐3.0), total parotidectomy with facial nerve sacrifice versus lesser extent of parotidectomy (aOR: 2.3, 95% CI: 1.7‐3.0), and simultaneous reconstructive procedures versus none (P < .001 for all). These features were similarly independently associated with prolonged LOS (P < .001 for all). Complication rates were universally low.ConclusionThe majority of superficial parotidectomies in this country are performed as outpatient procedures requiring <3 hours of operative time, with low complication rates. Malignant tumors, greater extent of parotidectomy, and simultaneous procedures were independently associated with prolonged operative time and LOS. These national benchmarks can inform operating room and hospital bed resource assignments.

ObjectiveThe purpose of this study was to evaluate the performance of advanced large language models from OpenAI (GPT‐3.5 and GPT‐4), Google (PaLM2 and MedPaLM), and an open source model from Meta (Llama3:70b) in answering clinical test multiple choice questions in the field of otolaryngology—head and neck surgery.MethodsA dataset of 4566 otolaryngology questions was used; each model was provided a standardized prompt followed by a question. One hundred questions that were answered incorrectly by all models were further interrogated to gain insight into the causes of incorrect answers.ResultsGPT4 was the most accurate, correctly answering 3520 of 4566 questions (77.1%). MedPaLM correctly answered 3223 of 4566 (70.6%) questions, while llama3:70b, GPT3.5, and PaLM2 were correct on 3052 of 4566 (66.8%), 2672 of 4566 (58.5%), and 2583 of 4566 (56.5%) questions. Three hundred and sixty‐nine questions were answered incorrectly by all models. Prompts to provide reasoning improved accuracy in all models: GPT4 changed from incorrect to correct answer 31% of the time, while GPT3.5, Llama3, PaLM2, and MedPaLM corrected their responses 25%, 18%, 19%, and 17% of the time, respectively.ConclusionLarge language models vary in their understanding of otolaryngology‐specific clinical knowledge. OpenAI's GPT4 has a strong understanding of core concepts as well as detailed information in the field of otolaryngology. Its baseline understanding in this field makes it well‐suited to serve in roles related to head and neck surgery education provided that the appropriate precautions are taken and potential limitations are understood.Level of EvidenceNA Laryngoscope, 135:629–634, 2025

ImportanceAsymmetric oropharynx uptake on positron emission tomography (PET)/computed tomography (CT) is a common incidental finding and often prompts otolaryngology referral to rule out malignancy; however, the true risk of malignancy based on this finding is unknown.ObjectiveTo identify the incidence of oropharynx cancer in patients with incidental asymmetric oropharynx PET uptake.Design, Setting, and ParticipantsIn this retrospective cohort study, patients 18 years and older undergoing PET/CT scans at Mayo Clinic between January 2001 and December 2018 were included. Patients with a history or pretest suspicion of oropharynx cancer were excluded. Data were analyzed from March 2021 to December 2023.ExposureBlinded radiologic review of imaging studies, including measurement of maximum standardized uptake values (SUVmax) of the ipsilateral side of concern and contralateral side. Retrospective medical record review for associated clinical data.Main Outcomes and MeasuresThe primary study outcome was the incidence of oropharynx cancer diagnosis in patients with asymmetric oropharynx PET uptake. The primary outcome was formulated before data collection.ResultsOf the 1854 patients identified with asymmetric oropharynx PET uptake, 327 (17.6%) met inclusion criteria. Of these, 173 (52.9%) were male, and the median (range) age was 65.0 (24.8-90.7) years. The mean (SD) follow-up interval was 52.1 (43.4) months. A total of 18 of 327 patients (5.5%) were newly diagnosed with oropharynx cancer. The most common diagnosis was squamous cell carcinoma (n = 9), followed by lymphoma (n = 8), and sarcoma (n = 1). Patients with an incidental diagnosis of oropharynx cancer had higher mean (SD) ipsilateral SUVmax (8.7 [3.7] vs 5.3 [1.9]) and SUVmax ratio (3.0 [1.6] vs 1.6 [0.6]) compared with patients with normal examination findings. SUVmax ratio and difference were found to be good discriminators of oropharynx cancer, with areas under the receiver operating characteristic curve of 86.3% (95% CI, 76.4-94.6) and 85.8% (95% CI, 74.8-94.6), respectively. Patients with a new diagnosis of oropharynx cancer were more likely to have a corresponding CT abnormality than those with normal examination findings (6 of 18 [33%] vs 24 of 295 [8.1%]). Patients with concerning lesions on oropharynx palpation by an otolaryngology health care professional were significantly more likely to be diagnosed with oropharynx cancer compared with patients with normal examination findings (odds ratio, 28.4; 95% CI, 6.6-145.8).Conclusions and RelevanceIn this cohort study, while incidental asymmetric oropharynx PET uptake was common, a new diagnosis of oropharynx cancer was not and potentially results in a large volume of unnecessary referrals and work-up. Using SUVmax ratio, SUVmax difference, and CT correlation may increase the benefit of referral. Patients with a palpable oropharynx lesion and asymmetric oropharynx PET uptake should undergo confirmatory biopsy.

Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.

Abstract Background: Analyzing interactions and the microanatomical distribution of the tumor immune microenvironment (TIME) is essential for a comprehensive understanding of tumor progression. Imaging Mass Cytometry (IMC) is a high-dimensional tissue imaging system that enables the deeper and multiparametric in situ exploration of tumor microenvironments at a single-cell level. This study describes a pipeline for analyzing 39-plex IMC images of human HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) tumor sections, elucidating immune cells' nature, functions, and interactions with tumor cells. The IMC data analysis provides valuable information for clinical studies that could be used for the identification of prognostic biomarkers and mechanisms of resistance to current immunotherapies. Methods: A retrospective study was conducted on (N=20) patients (10 progressors and 10 non-progressors) with HPV(+) OPSCC. The dataset comprises paired hematoxylin and eosin (H&E) images with IMC data from multiple Regions of Interest (ROIs) (N=82), enabling the in-situ profiling of 39 proteins in primary tumor tissue. Cell segmentation was followed by employing original images and their segmentation masks for cell phenotype identification using a probabilistic neural network method to spatially profile cancer cells, macrophages, NK-M cells, B-cells, and distinct T-cell populations. We identified protein expression at single-cell resolution and investigated the impact of multicellular spatial organization on the disease progression. The spatial neighborhood interaction score of tumor cells with various other cells was computed for all the ROIs across the two groups. Results: The markers showed varying expression levels of intensity distribution, likely due to differences in tissue sample composition. Specifically, CD3, CD4, CD8, CD19, CD20, and CD68 showed significantly higher intensity in non-progressors. Interestingly, FoxP3 also had a significantly higher intensity level in non-progressors. Cell phenotyping emphasized that non-progressors generally have increased levels of NK-M cell markers. Spatial analysis revealed a significant increase in interaction between CD3 cells and tumor cells in non-progressors (p-value=0.07, Mann-Whitney U test). Furthermore, a significant rise in the interaction between B-cells and FoxP3+ cells was observed in non-progressors (p-value&lt;0.05, Mann-Whitney U test) suggesting a coordinated suppression of tumor growth. Conclusion: We developed a deep learning-based pipeline to analyze spatial relationships in the TIME of IMC data, demonstrating its clinical relevance in predicting disease progression. Our findings emphasize the importance of spatial relationships in the TME for response and suggest that proximity between either CD3+ T-cells to cancer cells or B-cells to FoxP3+ cells are candidate biomarkers. Citation Format: Sumanth Reddy Nakkireddy, Routman David, Kathleen Bartemes, Daniel Ma, Tae Hyun Hwang, Kathryn Van Abel, Chadi Nimeh Abdel-Halim. AI-enhanced spatial proteomics reveals B-cells & FoxP3+ cells interactions in HPV(+) oropharyngeal squamous cell carcinoma Progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5488.

Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient’s quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. Conclusions: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.