Yin, Linda X.

Abstract Objective To (1) track the incidence of pleomorphic adenomas (PAs) and (2) compare demographic and treatment trends in PAs over the last five decades in a single county. Study Design Retrospective cohort of all patients with a pathologic diagnosis of nonrecurrent PA from January 1976 to December 2022. Setting Olmsted County, Minnesota. Methods Incidence was calculated per 100,000 persons/year and age and sex‐adjusted to the US 2020 census data. Incidence trends were identified using Poisson rate regression models. Changes in clinical features of diagnosis were evaluated using Spearman rank correlation coefficient tests, Wilcoxon rank sum tests, and Kruskal‐Wallis tests. Results In total, 251 patients with PA were identified. The median age at diagnosis was 50.0 years with a slight female predominance (1.24:1). The adjusted incidence during this period is 4.79/100,000 person‐years, increasing from 2.50 in 1976 to 1979 to 5.73/100,000 persons/year in 2020 to 2022. Less extensive surgery, including partial and superficial parotidectomies, increased significantly from 1976 to 2022, whereas total parotidectomies decreased ( P < .0001). The number of patients who presented with an incidental imaging finding increased during this time period ( P < .001), as did the age at diagnosis (45‐51 years, P = .05) Conclusion The average annual incidence of PAs in Olmsted County from 1976 to 2022 is higher than reported US estimates and has increased over the last five decades. The percentage of patients who presented with incidental imaging findings increased over this period, as did the age at diagnosis. These findings highlight modern imaging techniques and an aging population more willing to seek workup and treatment of a benign parotid mass.

Objective: To assess the impact of extent of parotidectomy on surgical and oncologic outcomes in low grade mucoepidermoid carcinoma (LGMEC). Methods: A retrospective chart review of all patients undergoing primary surgical treatment for LGMEC from 2000 to 2022 was conducted. Clinical features collected included demographics, facial nerve function, operative techniques, postoperative complications/facial nerve function, and recurrence. Results: 58 patients were included; 10 patients underwent partial parotidectomy (PP), 38 underwent superficial parotidectomy (SP), and 10 underwent near-total/total parotidectomy. PP and SP patients had smaller tumors and more superficial tumors compared to near-total/total parotidectomy group ( P = .03). PP and SP were more likely to have negative margins and less locoregional disease compared to near-total/total parotidectomy patients ( P < .01). Near-total/total parotidectomy were more likely to undergo facial nerve resection (20% vs 0% for PP & SP respectively) ( P = .05). Immediate postoperative facial nerve function was significantly better among PP patients (73% HB I) compared to SP (44% HB I) and near-total/total parotidectomy patients (0% HB I) ( P < .01). Most patients regained their facial nerve function although only 40% of the near-total/total parotidectomy patients had a HB I at the time of last follow up ( P < .01). Patients were followed for a median of 6.2 years, during which only 1 patient (total parotidectomy) had a recurrence. Conclusions: PP offers a safe and effective approach for small LGMEC tumors, ensuring better facial nerve function postoperatively with minimal complications compared to more extensive surgery.

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 &amp;gt;40 years). Phase II enrolled 342 participants, of whom 317 completed the survey (305 women [89%]; 284 participants [83%] aged &amp;gt;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.

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.

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.

Abstract Although the majority of HPV (+) oropharyngeal squamous cell carcinoma (OPSCC) patients exhibit a favorable prognosis, approximately 20% face recurrent or metastatic disease, posing management challenges. Therefore, the identification of robust prognostic markers for risk stratification is essential. Our study focused on the comprehensive characterization of intratumor heterogeneity within the tumor immune microenvironment (TME) in both primary tumors and metastatic lymph nodes. Utilizing computational approaches, we integrated hematoxylin and eosin (H&E) and 11 adjacent immunohistochemistry (IHC)-stained slides to investigate the cellular composition and functional characteristics across different regions within the TME. Based on these detailed immune characteristics, we classified patients into specific immune subtypes. Our integrative TME analysis indicated that patients with high tumor-infiltrating lymphocytes (TIL), increased CD8 + levels, and reduced CD163 + cell counts within their primary tumors were likely to have a more favorable progression-free survival outcome. The integration of H&E and IHC data enhances the functional characterization of immune phenotypes of the TME with biological interpretability and improves patient stratification in HPV(+) OPSCC.

ImportanceLimited literature exists on surgical outcomes after selective deep lobe parotidectomy (SDLP) with preservation of superficial lobe for patients with benign deep lobe tumors.ObjectiveTo compare the following factors for SDLP vs total parotidectomy for patients with benign tumors in the deep lobe: postoperative complications, including facial nerve paresis or paralysis, Frey syndrome, first bite syndrome, cosmetic defect, sialocele formation, and wound infection; and tumor control and recurrence.Design, Setting, and ParticipantsThis case series included 273 adults who underwent SDLP (n = 177) or total parotidectomy (n = 96) at a single tertiary care institution for benign parotid tumors located in the deep lobe or deep lobe and parapharynx from January 1, 2000, to December 31, 2020.ExposureSelective deep lobe parotidectomy vs total parotidectomy.Main Outcomes and MeasuresIncidence of postoperative complications and tumor recurrence.ResultsAmong 273 patients (SDLP, 177 [65%]; 122 women [69%]; median age at surgery, 58 years [IQR, 46-67 years]; total parotidectomy, 96 [35%]; 57 women [59%]; median age at surgery, 59 years [IQR, 40-68 years]), the most common tumor was pleomorphic adenoma (SDLP, 128 of 177 [72%]; total parotidectomy, 62 of 96 [65%]). An abdominal dermal fat graft was less commonly performed for patients who underwent SDLP than those who underwent total parotidectomy (2 of 177 [1%] vs 20 of 96 [21%]; difference, −20% [95% CI, −28% to −11%]). The rate of great auricular nerve preservation was higher in the SDLP group than in the total parotidectomy group (84 of 102 [82%] vs 20 of 34 [59%]; difference, 24% [95% CI, 5%-42%]). No meaningful difference in length of hospital stay was found. The percentage of patients with House-Brackmann grade I immediately after surgery was 48% (85 of 177) in the SDLP group and 21% (20 of 96) in the total parotidectomy group (difference, 28% [95% CI, 16%-40%]). There were no clinically meaningful differences in rates of hematoma, sialocele, seroma, ear numbness, wound infection, or unplanned return to emergency department or operating room. The SDLP group reported a lower rate of Frey syndrome than the total parotidectomy group (1 of 137 [1%] vs 12 of 78 [15%]; difference, −15% [95% CI, −23% to −7%]), as well as a lower rate of facial contour defect (28 of 162 [17%] vs 25 of 84 [30%]; difference, −13% [95% CI, −24% to −1%]) and a higher rate of first bite syndrome (34 of 148 [23%] vs 7 of 78 [9%]; difference, 14% [95% CI, 5%-23%]). The percentage of patients with House-Brackmann grade I at their first follow-up visit was 67% (118 of 177) in the SDLP group compared with 49% (47 of 96) in the total parotidectomy group (difference, 17% [95% CI, 4%-30%]). There was no clinically meaningful difference in House-Brackmann grade after 1 year.Conclusions and RelevanceFindings of this case series study suggest that SDLP can be considered an effective and even superior technique for management of benign tumors in the deep parotid lobe. Advantages associated with SDLP include reduction in need for reconstruction for facial contour defect and reduction in complications, such as immediate facial nerve weakness and Frey syndrome. The incidence of first bite syndrome was higher in the SDLP group. Tumor control was not compromised by SLDP.