Head and Neck Merkel Cell Carcinoma: Therapeutic Benefit of Adjuvant Radiotherapy for Nodal Disease.

OBJECTIVES: To evaluate the therapeutic effect of post-operative radiotherapy (PORT) with respect to nodal status among patients with head and neck Merkel cell carcinoma (HNMCC). METHODS: In this retrospective study, we queried Surveillance, Epidemiology, and End Results (SEER) dataset from 2000 through 2019. We included all adult patients who received primary surgical resection for histologically confirmed treatment naive HNMCC. Entropy balancing was used to reweight observations such that there was covariate balance between patients who received PORT and patients who received surgical resection alone. Doubly robust estimation was achieved by incorporating weights into a multivariable cox proportional hazards model. Planned post hoc subgroup analysis was performed to evaluate the impact of PORT by pathological node status. RESULTS: Among 752 patients (mean age, 73.3 years [SD 10.8]; 64.2% male; 91.2% White; 41.9% node-positive), 60.4% received PORT. Among node-positive patients, we found that PORT was associated with improved overall survival (OS) (aHR, 0.55; 95% CI, 0.37-0.81; p = 0.003) and improved disease-specific survival (DSS) (aHR, 0.57; 95% CI, 0.35-0.92; p = 0.022). Among node-negative patients, we found that PORT was not associated with OS and was associated with worse DSS (aHR, 2.34; 95% CI, 1.30-4.23; p = 0.005). CONCLUSIONS: We found that PORT was associated with improved OS and DSS for node-positive patients and worse DSS for node-negative patients. For HNMCC treated with primary surgical resection, these data confirm the value of PORT for pathologically node-positive patients and support the use of single modality surgical therapy for pathologically node-negative patients without other adverse risk factors. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Electromyography findings in radiation-induced unilateral tongue immobility.

BACKGROUND: We used electromyography to characterize hypoglossal nerve function among radiation-treated head and neck cancer survivors with later onset unilateral tongue immobility. METHODS: Patients with unilateral tongue immobility without evidence of recurrent cancer were seen at a tertiary academic institution between February and September 2021. All patients were at least 2 years post-treatment with radiation therapy for head and neck squamous cell carcinoma. Participants were under annual surveillance and displayed no evidence of operative injury to the hypoglossal nerve. RESULTS: The median symptom-free interval for the 10 patients included in this study was 13.2 years (range 2-25 years). Myokymia alone was present in 3 of 10 patients, fibrillation potentials alone were present in 3 of 10 patients, and 1 subject displayed both fibrillation and myokymia. Three out of 10 patients had normal hypoglossal nerve function. DISCUSSION: These findings highlight how disparate mechanisms may underlie similar clinical presentations of radiation-induced neuromuscular dysfunction.

Postoperative Radiotherapy and Survival in Oral Cavity Squamous Cell Carcinoma With Mandibulectomy.

Importance: Oral cavity squamous cell carcinoma (SCC) tumors with mandibular invasion are upstaged to pT4a regardless of their size. Even small tumors with boney invasion, which would otherwise be classified as pT1-2, are recommended for the locally advanced treatment pathway to receive administration of postoperative radiotherapy (PORT). Objective: To evaluate the association of PORT with overall survival according to tumor size among patients who received mandibulectomy for pT4aN0 oral cavity SCC. Design, Setting, and Participants: This was a retrospective analysis using data from the US National Cancer Database from January 1, 2004, through December 31, 2019. All patients who received mandibulectomy for treatment-naive pT4aN0 oral cavity SCC with negative surgical margins were included. Data analyses were performed in January 2023 and finalized in July 2023. Exposure: PORT vs no PORT. Main Outcomes and Measures: Entropy balancing was used to balance covariate moments between treatment groups. Weighted multivariable Cox proportional hazards regression was used to measure the association of PORT with overall survival associated with tumor size. Results: Among 3268 patients with pT4aN0 oral cavity SCC (mean [SD] age, 65.9 [12.1] years; 2024 [61.9%] male and 1244 [38.1%] female), 1851 (56.6%) received PORT and 1417 (43.4%) did not receive PORT. On multivariable analysis was adjusted for age, insurance status, Charlson Comorbidity Index score, tumor site, tumor grade, tumor size, and PORT. Findings indicated that PORT was associated with improved overall survival and that this relative survival advantage trended upwards with increasing tumor size. That is, the larger the tumor, the greater the survival advantage associated with the use of PORT. For the 1068 patients with tumors greater than 4 cm, the adjusted hazard ratio (aHR) in favor of PORT was 0.63 (95% CI, 0.48-0.82); for the 1774 patients with tumors greater than 2 cm but less than or equal to 4 cm, the aHR was 0.76 (95% CI, 0.62-0.93); and for 426 patients with tumors less than 2 cm, the aHR was 0.81 (95% CI, 0.57-1.15). Conclusions and Relevance: In this retrospective analysis of patients who received mandibulectomy for pT4aN0 oral cavity SCC, PORT was associated with improved overall survival, the benefit of which improved relatively with increasing tumor size. These findings suggest that tumor size should be considered in guidelines for PORT administration in this patient population.

Subcategorization of Perineural Invasion Stratifies Oral Cavity Squamous Cell Carcinoma Prognosis.

OBJECTIVE: To evaluate whether subcategorization of perineural invasion (PNI) improves the prognostic resolution of the American Joint Committee on Cancer, Eighth Edition (AJCC8) staging system in oral cavity squamous cell carcinoma (OCSCC). METHODS: OCSCC tumor specimens from patients seen at a tertiary care institution who underwent primary surgical resection between January 2019 and June 2021 were sorted into four PNI categories: negative, intratumoral, peripheral, and extratumoral. The prognostic effect of these PNI categories were assessed through Kaplan-Meier, Cox regression, and log-rank testing using recurrence-free survival (RFS) and overall survival (OS) as primary and secondary outcomes respectively. RESULTS: A total of 158 patients were examined. The median follow-up time was 21 months. PNI subcategorization further stratified RFS (p = 0.007) and OS (p = 0.002). Extratumoral PNI was associated with a 4.5-fold increase in recurrence risk (adjusted hazards ratio [aHR]: 4.53; 95% confidence interval [CI]: 1.1-18.66) and worse OS when compared with PNI negative disease (aHR: 5.71; 95% CI: 1.0-32.67). Peripheral PNI was associated with worse OS (aHR: 5.7; 95% CI: 1.35-24.08) but not worse RFS (p = 0.18) when compared with PNI negative disease. Interestingly, intratumoral PNI was not associated with significant differences in RFS (p = 0.087) or OS (p = 0.22) when compared with PNI negative disease. CONCLUSIONS: Subcategorization of OCSCC tumors into extratumoral, peripheral, and intratumoral PNI stratifies RFS and OS when compared with patients with PNI negative disease in an incremental fashion. This pilot study suggests that there may be added benefit in subcategorization of PNI in the prognostic evaluation of OCSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1656-1662, 2024.

The pediatric indications for tonsillectomy and adenotonsillectomy: Race/ethnicity, age, and gender.

Objective: To evaluate how pediatric indications for tonsillectomy or adenotonsillectomy relate to gender, race/ethnicity, and age. Methods: Included consecutive pediatric patients who underwent tonsillectomy or adenotonsillectomy from a single tertiary academic institution between 2012 and 2019. Logistic regression analysis was used to measure association between the indication for tonsillectomy and the demographic variables gender, race/ethnicity, and age. Results: Of the 1106 children included in this study, 53% were male and 47% were female. Half of the children were White, 40% were African American, 6% were Hispanic and 4% were other. The most common indication for surgery was upper airway obstruction alone (66%), followed by obstruction and infection (22%), and recurrent infections (12%). We found that male gender (OR 1.59, 95% CI 1.24-2.04), African American race (OR 2.76, 95% CI 2.08-3.65), and younger age were associated with greater odds of presenting with upper airway obstruction as the indication for tonsillectomy. Conversely, male gender (OR 0.63, 95% CI 0.44-0.92), African American race (OR 0.4, 95% CI 0.26-0.61), and younger age were associated with lower odds of presenting with recurrent infection as the indication for tonsillectomy. Conclusions: Male gender, African American race, and young age are risk factors for tonsillar surgery due to airway obstruction. Female gender, White race, and older age are risk factors for tonsillar surgery due to recurrent throat infections. Level of Evidence: 3.

Health Literacy and Adherence to Clinical Recommendations in Head and Neck Cancer.

BACKGROUND: After definitive cancer treatment, survivors of head and neck cancer (HNC) are commonly recommended to participate in therapies aimed at reducing the burden of treatment-related side effects. OBJECTIVE: In this study, we evaluated whether adherence to referral to physical therapy (PT) and speech-language pathology therapy (SLPT) is related to patient health literacy (HL). METHODS: This is a retrospective cohort analysis of patients attending a multidisciplinary HNC survivorship clinic between 2017 and 2019. HL was measured using the Brief Health Literacy Screen, with scores below 10 indicating inadequate HL. Chi-square and logistic regression were used to evaluate the association between HL and adherence to PT or SLPT referral. KEY RESULTS: From the overall cohort (N = 454), 80 patients (18%) had inadequate HL. Compared to those with adequate HL, patients with inadequate HL were significantly less likely to complete initial PT evaluation (74% vs. 58%, p = .034) but were not significantly less likely to complete initial SLPT evaluation (70% vs. 61%, p = .37). After adjusting for age, primary tumor site, and treatment stage, we found that patients with inadequate HL were half as likely to follow up for initial PT evaluation (odds ratio 0.45, p = .032). CONCLUSION: Overall, inadequate HL is associated with reduced adherence to PT but is not associated with adherence to SLPT among HNC survivors. These results highlight the clinical importance of HL and underscore the need for interventions to facilitate adherence to treatment for patients with inadequate HL. [HLRP: Health Literacy Research and Practice. 2023;7(1):e52-e60.].

Local Tumor Behavior Associated With Survival Among Patients With Paraganglioma of the Head and Neck.

Objective: The purpose of this study was to evaluate the utility of ICD-O-3-classified local tumor behavior as a prognosticator of head and neck paraganglioma (HNP) outcomes. Study Design: Retrospective cohort study. Setting: National Cancer Database between 2004 and 2016. Methods: This study included patients aged ≥18 years who were diagnosed with HNP. Clinical outcomes and clinicopathologic features were compared with regard to local tumor behavior. Results: Our study included 525 patients, of which the majority had HNP classified as locally invasive (45.9%) or borderline (37.9%). The most common anatomic sites involved were the carotid body (33.7%), intracranial regions (29.0%), or cranial nerves (25.5%). Carotid body tumors were exclusively locally invasive, whereas intracranial and cranial nerve HNP were overwhelmingly benign or borderline (94% and 91%, respectively). One-fourth of patients underwent pathologic analysis of regional lymph nodes, of which the majority were positive for metastasis (80.6%). Metastasis to distant organs was twice as common in patients with locally invasive tumors vs benign (15% vs 7.1). For benign disease, surgery with radiotherapy (adjusted hazard ratio [aHR], 40.45; P = .006) and active surveillance (aHR, 24.23; P = .008) were associated with worse survival when compared with surgery alone. For locally invasive tumors, greater age (aHR, 1.07; P < .0001) and positive surgical margins (aHR, 4.13; P = .010) were predictors of worse survival, while combined surgery and radiotherapy were predictors of improved survival vs surgery alone (aHR, 0.31; P = .027). Conclusion: While criteria for tumor behavior could not be defined, our results suggest that such a classification system could be used to enhance HNP risk stratification and guide clinical management decisions.