Smoking and other patient factors in HPV-mediated oropharynx cancer: A retrospective cohort study.

PURPOSE: To characterize the significance of patient-level influences, including smoking history, on oncologic outcomes in human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC). MATERIALS AND METHODS: A bi-institutional retrospective cohort study of previously untreated, HPV+ OPC patients who underwent curative treatment from 1/1/2008 to 7/1/2018 was performed. The primary outcome was disease-free survival (DFS) and the primary exposure was ≤10 versus >10-pack-year (PY)-smoking history. RESULTS: Among 953 OPC patients identified, 342 individuals with HPV+ OPC were included. The median patient age was 62 years, 33.0% had a > 10-PY-smoking history, 60.2% had AJCC8 stage I disease, and 35.0% underwent primary surgery. The median follow-up was 49 months (interquartile range [IQR] 32-75 months). Four-year DFS-estimates were similar among patients with ≤10-PY-smoking history (78.0%, 95% CI:71.7%-83.1%) compared to >10-PYs (74.8%; 95% CI:65.2%-82.0%; log-rank:p = 0.53). On univariate analysis, >10-PY-smoking history did not correlate with DFS (hazard ratio[HR]:1.15;95% CI:0.74-1.79) and remained nonsignificant when forced into the multivariable model. On adjusted analyses, stage, treatment paradigm, and age predicted DFS. Neither >10-PYs, nor any other definition of tobacco use (e.g., current smoker or > 20-PYs) was predictive of DFS, overall survival, or disease-specific survival. Conversely, age nonsignificantly and significantly predicted adjusted DFS (adjusted HR[aHR]:1.02,95% CI:0.997-1.05, p = 0.08), overall survival (aHR 1.05; 95% CI: 1.02-1.08; p = 0.002) and disease-specific survival (aHR 1.04;95% CI: 0.99-1.09;p = 0.09). CONCLUSION: Other than age, patient-level influences may not be primary drivers of HPV+ OPC outcomes. Although limited by its modest sample size, our study suggests the significance of smoking has been overstated in this disease. These findings and the emerging literature collectively do not support risk-stratification employing the >10-PY threshold. LEVEL OF EVIDENCE: Level 4.

Recurrent oropharyngeal squamous cell carcinomas maintain anti-tumor immunity and multinucleation levels following completion of radiation.

Objective: Oropharyngeal squamous cell carcinoma (OPSCC) recurrence is almost universally fatal. Development of effective therapeutic options requires an improved understanding of recurrent OPSCC biology. Methods: We analyzed paired primary-recurrent OPSCC from Veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who received curative intent radiation-based treatment (with or without chemotherapy). Patient tumors were analyzed using standard immunohistochemistry and automated imaging of infiltrating lymphocytes and multinucleated tumor cells coupled to machine learning algorithms. Results: Primary and recurrent tumors demonstrated high concordance via p16 and p53 immunohistochemistry, with comparable levels of multinucleation. In contrast, recurrent tumors demonstrated significantly higher levels of CD8+ tumor infiltrating lymphocytes (p<0.05) and higher levels of PD-L1 expression (p<0.05). Conclusion: Exposure to chemo-radiation and recurrence following treatment does not appear deleterious to underlying biological characteristics and anti-tumor immunity of oropharyngeal cancer, suggesting that novel treatment regimens may be as effective in the salvage setting as in the definitive intent setting.

Recurrent Oropharyngeal Squamous Cell Carcinomas Maintain Anti-tumor Immunity and Multinucleation Levels Following Completion of Radiation.

OBJECTIVE: Oropharyngeal squamous cell carcinoma (OPSCC) recurrence is almost universally fatal. Development of effective therapeutic options requires an improved understanding of recurrent OPSCC biology. METHODS: We analyzed paired primary-recurrent OPSCC from Veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who received curative intent radiation-based treatment (with or without chemotherapy). Patient tumors were analyzed using standard immunohistochemistry and automated imaging of infiltrating lymphocytes and multinucleated tumor cells coupled to machine learning algorithms. RESULTS: Primary and recurrent tumors demonstrated high concordance via p16 and p53 immunohistochemistry, with comparable levels of multinucleation. In contrast, recurrent tumors demonstrated significantly higher levels of CD8+ tumor infiltrating lymphocytes (p<0.05) and higher levels of PD-L1 expression (p<0.05). CONCLUSION: Exposure to chemo-radiation and recurrence following treatment preserves critical features of intrinsic tumor biology and the tumor immune microenvironment suggesting that novel treatment regimens may be as effective in the salvage setting as in the definitive intent setting.

Obstructive Sleep Apnea in Underweight Children.

OBJECTIVES: To determine predictors of obstructive sleep apnea (OSA) in underweight children and to describe the demographic, clinical, and polysomnographic characteristics of an ethnically diverse population of underweight children with OSA. STUDY DESIGN: Case-control study. SETTING: University of Texas Southwestern Medical Center and Children's Medical Center of Dallas. METHODS: Underweight children aged 2 to 18 years who underwent a polysomnogram for suspected OSA between January 2014 and December 2020 were included. Underweight was defined as body mass index <5th percentile per Centers for Disease Control and Prevention guidelines. Children with apnea-hypopnea index <1.0 served as a control group. Univariate and multiple logistic regression analysis was used to determine the predictors of OSA. Significance was set at P < .05. RESULTS: An overall 124 children met inclusion criteria: mean age, 6.4 years; 50% female; 44% Hispanic, 31% African American, and 18% Caucasian. A total of 83 children had OSA (apnea-hypopnea index ≥1.0). Height was negatively correlated with OSA (odds ratio, 0.94; 95% CI, 0.88-0.99; P = .02) while allergic rhinitis (odds ratio, 2.97; 95% CI, 1.24-7.08; P = .01) and tonsillar hypertrophy (odds ratio, 3.38; 95% CI, 1.42-8.02; P = .01) were predictors for the presence of OSA. No demographic or clinical characteristics were predictors for severe OSA. CONCLUSION: Underweight children with OSA, as compared with those without OSA, are more likely to have decreased height, tonsillar hypertrophy, and allergic rhinitis. There are no predictors of severe OSA in underweight children. We recommend polysomnography for the diagnosis of OSA in symptomatic underweight children with large tonsils, especially when they have a history of allergies.

Adolescent Tracheostomy for COVID-19 Respiratory Failure.

Pediatric tracheostomy for COVID-19 infections is uncommon and requires age-appropriate adaptations. This case adds to a limited body of literature related to tracheostomy placement and management in an adolescent. Thoughtful planning and communication by a dedicated tracheostomy team was crucial in obtaining a successful outcome.