Van Abel, Kathryn M

AbstractObjectiveLow‐grade parotid malignancies have high overall survival rates; however, controversy remains about the appropriate extent of surgery. We aim to explore the trends in the extent of parotidectomy performed over time in low‐grade parotid malignancies in the United States, with a hypothesis that there has been a trend towards less aggressive surgery.Study DesignRetrospective cohort study of all low‐grade (grade I) acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC) in the Surveillance, Epidemiology, and End Results (SEER) from 2004 to 2020.SettingGeographic areas served by SEER.MethodsTrends were assessed using Cochran‐Armitage tests and logistic regression; Kaplan‐Meier survival curves were used to analyze overall and cancer‐specific survival, and chi‐square tests were used to analyze patient characteristics.ResultsIn total, 1288 patients were identified (916 MEC; 372 ACC). Most patients (n = 772, 60%) were non‐Hispanic white, with an average age of 50.6 years and had a slight female predominance (1.58:1). Most of the cohort presented with tumor stage T1 or T2 (84%), N0 (90.1%), and M0 (96.9%). Treatment with total parotidectomy decreased significantly (34.6 vs 17.7%, P = .02) whereas sacrificing the facial nerve (FN) slightly decreased (20 vs 15.7%, P = .1). A significant increase in N0 patients (71%‐94%, P < .0001) was observed, whereas T staging remained stable (61%‐64%, P = .3). Overall, both ACC and MEC had excellent cancer‐specific survival.ConclusionOver the last 17 years, there has been a significant de‐escalation in the extent of parotidectomy for low‐grade parotid malignancy in the United States.

Background: Malignant mesenchymal tumors involving the parotid gland are uncommon, characteristically aggressive, and little is known with few reports documented. Study Design: Retrospective case series. Setting: Single institution tertiary care center, 2010 to 2022. Method: Patients were identified from an institutional parotid tumor database. Patient history, demographics, pathologic diagnosis, treatment, and follow up were documented. Results: Eight patients were identified, 3 were males. The average age was 61 years old, and the most common tumors identified were pleomorphic sarcomas (3 patients). Presenting symptoms included: preauricular/cheek mass in 7 patients, facial pain (4), otalgia (4), aural fullness (3), and numbness (1). All patients received a parotidectomy, and 4 patients received adjuvant therapy of either radiation or chemoradiation. Post-operatively, there were 3 cases of distant recurrence, 2 cases of regional recurrence, and 1 case of local recurrence. There were 2 reports of death. Conclusion: Malignant mesenchymal tumors of the parotid are rare, represent varied histologies. Due to their aggressive nature, surgical resection with radiation and close follow-up may be an appropriate treatment regimen in controlling the disease.

Importance Circulating tumor human papillomavirus DNA (ctHPVDNA) is an important biomarker for the presence of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but little is known about early postoperative kinetics of ctHPVDNA clearance. Objective To investigate early postoperative kinetics of ctHPVDNA in patients with HPV-associated OPSCC. Design, Setting, and Participants This prospective cohort study was conducted at a single tertiary care center from January 4, 2020, to January 26, 2023. Patients with newly diagnosed HPV-associated OPSCC undergoing surgical management were enrolled. HPV status was defined as positive if findings of p16 immunohistochemistry and/or HPV DNA in situ hybridization and/or E6/E7 RNA in situ hybridization were positive. Exclusion criteria included history of prior head and neck cancer and metastatic disease at presentation. Data were analyzed from September 1, 2024, to April 25, 2025. Exposures Transoral robotic surgery with concurrent neck dissection. Main Outcomes and Measures Blood was drawn prior to surgery (pretreatment), 1 to 2 days after surgery (postoperative days 1 to 2), and approximately 2 weeks after surgery (postoperative week 2; range, 8 to 20 days). ctHPVDNA was quantified by a tumor tissue–modified viral (TTMV) HPV DNA test. Correlations were tested between the pretreatment and postoperative day 1 to 2 TTMV HPV DNA levels using Gaussian regression. Concordance between detectability at postoperative day 1 to 2 and postoperative week 2 was explored using negative predictive value and positive predictive value. Results Of 57 included patients with detectable pretreatment TTMV HPV DNA, 51 (89%) were male, and the median (IQR) age was 59 (54-66) years. A total of 35 patients (61%) had blood draws at all 3 time points; 16 (28%) had detectable TTMV HPV DNA on postoperative day 1 to 2. Pretreatment and postoperative day 1 to 2 TTMV HPV DNA levels had a medium positive linear correlation ( r = 0.31; 95% CI, 0.04-0.54). Undetectable TTMV HPV DNA on postoperative day 1 to 2 blood draw had a negative predictive value of 0.95 (95% CI, 0.74-1.00) for an undetectable level on postoperative week 2 blood draw, but a detectable level on postoperative day 1 to 2 blood draw only had a positive predictive value of 0.19 (95% CI, 0.04-0.46). Of the 16 patients with detectable TTMV HPV DNA pretreatment and at postoperative day 1 to 2, only 3 (19%) continued to have detectable TTMV HPV DNA at postoperative week 2. One patient had undetectable levels at postoperative day 1 to 2 and detectable levels at postoperative week 2. Conclusions and Relevance In this study, ctHPVDNA detectability early after surgery did not predict detectability at 2 weeks after surgery. ctHPVDNA clearance early after surgery could predict a negative test at 2 weeks. A negative blood draw finding on postoperative day 1 may be used to omit a postoperative blood draw at 2 weeks for minimal residual disease detection in future clinical trials.

Importance A subset of Union for International Cancer Control ( UICC )/ American Joint Committee on Cancer ( AJCC ) eighth edition TNM stage I and II human papillomavirus–positive oropharyngeal carcinoma has undesirable outcomes, which might have contributed to a lack of success in phase III deintensification trials. Refining clinical stage groups, especially in the overabundant cN1/stage I group, has become important for treatment selection. Objective To assess the prognostic importance of pretreatment lymph node (LN) characteristics to optimize case distribution and outcome homogeneity within the N classification system. Design, Setting, and Participants This is an international multi-institutional retrospective prognostic cohort study. Analysis of human papillomavirus–positive oropharyngeal carcinoma treated curatively from 4 institutions (International Collaboration of Oropharyngeal Cancer Network for N-Classification [ICON-N] dataset) provided a refined clinical staging proposal; an independent dataset (Centre Hospitalier de l’Université de Montréal [CHUM] dataset) validated the proposal. Neuroradiologists reviewed pretreatment computed tomography and/or magnetic resonance imaging for nodal features, including presence or absence of abnormal LN(s), retropharyngeal LN, laterality, number of abnormal LN, and imaging-detected extranodal extension (iENE). Data were collected from February to May 2023, and data were analyzed from June to July 2023. Exposures Definitive chemoradiotherapy/radiotherapy or definitive surgery with or without postoperative chemoradiotherapy/radiotherapy. Main Outcomes and Measures The primary end point was overall survival. A Cox proportional hazards multivariable model was used to estimate adjusted hazard ratios (AHRs) and to derive an optimal clinical TNM stage classification (AHR-stage schema) incorporating the strongest prognostic nodal features within the UICC/AJCC eighth edition TNM framework after confirming the prognostication of iENE status. The performance (according to overall normalized scores and ranking) of the AHR-stage schema against the current UICC/AJCC eighth edition TNM staging system was evaluated for hazard consistency, hazard discrimination, prognostic importance, and sample size balance. Validation was performed in the CHUM dataset. Results The ICON-N dataset comprised 2053 patients, including 1898 (92.5%) with cN-positive disease and 155 (7.5%) with cN0 disease; a total of 298 (14.5%) were female, and the mean (SD) age was 60.6 (9.3) years. iENE-positive disease was identified in 710 of 1898 patients with cN-positive disease (37.4%). The median (range) follow-up was 5.1 (0.1-14.7) years. iENE was the strongest prognostic nodal feature in multivariable analysis; the AHR for iENE-positive vs iENE-positive disease was 2.43 (95% CI, 1.96-3.03) in the ICON-N dataset and 2.04 (95% CI, 1.28-3.23) in the CHUM dataset (n = 451). Reclassifying iENE-positive cases 1 stratum higher for N categorization without altering iENE-negative cases yielded an AHR-stage schema that outperformed the current TNM staging system in disease-free and overall survival with a lower (ie, better) overall normalized score (2 vs 3). Conclusions and Relevance In this study, reclassifying each N category 1 stratum higher for iENE-positive disease resulted in better disease-free and overall survival. The proposed new classification outperformed the currently TNM staging system in risk stratification and may facilitate future clinical trial design, outcomes research, and patient care.

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.