Trends of Ten Leading Causes of Death in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: An understanding of the leading causes of death in patients with head and neck squamous cell carcinoma (HNSCC) would be helpful to inform doctors, patients, and healthcare providers on disease management. This study aimed to comprehensively study the leading causes of death in these survivors. METHODS: We investigated the trends of risk factors for major causes of death in patients with HNSCC. Causes of death in HNSCC were obtained from the Surveillance, Epidemiology, and End Results registries. We characterized trends in the 5-year cumulative mortality as well as risk factors associated with the ten leading causes of death. RESULTS: Among 48 297 deaths identified, the ten leading causes were as follows: HNSCC, heart disease, lung cancer, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, pneumonia & influenza, accidents & adverse effects, esophagus cancer, chronic liver diseases, and septicemia. Non-HNSCC deaths surpassed HNSCC deaths 4 years after cancer diagnosis. There was a significant decline in the 5-year cumulative mortality from HNSCC, heart disease, lung cancer, COPD, cerebrovascular disease, and esophagus cancer. The risks of mortality from the ten leading causes varied with patient characteristics. CONCLUSION: Our findings provide a useful picture of mortality patterns in HNSCC survivors, which might help when planning personalized HNSCC care.

The primary site of head and neck squamous cell carcinoma predicts survival benefits of EGFR inhibitors: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: To assess the survival benefits associated with epidermal growth factor receptor (EGFR) inhibitors in head and neck squamous cell carcinoma (HNSCC) according to the primary site. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted for randomized phase III trials comparing treatment with or without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCC. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Data were pooled using a random-effects model. RESULTS: Seven trials with a total of 3391 patients were included. The addition of EGFR inhibitors improved OS in patients with oral cavity-oropharyngeal carcinoma (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.67-0.87, P < 0.001) but not in patients with hypopharyngeal-laryngeal carcinoma (HR 0.94, 95% CI 0.82-1.08, P = 0.398). A significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.029). The addition of EGFR inhibitors increased PFS in both patients with oral cavity-oropharyngeal carcinoma (HR 0.67, 95% CI 0.52-0.85, P = 0.001) and patients with hypopharyngeal-laryngeal carcinoma (HR 0.81, 95% CI 0.69-0.94, P = 0.005). A trend towards significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.161). Comparable results were observed in the pre-specified subgroup analyses. Meta-regression analyses suggested that the primary site appeared to be a predictor of survival benefits in HNSCC patients who received treatment with EGFR inhibitors over those who did not. CONCLUSION: Our meta-analysis suggests that the survival benefits of EGFR inhibitors might depend on primary sites in HNSCC. Further studies are needed to confirm this finding.

Difference in tumor mutation burden between squamous cell carcinoma in the oral cavity and larynx.

OBJECTIVES: This study aimed to evaluate the difference in tumor mutation burden (TMB) between oral cavity squamous cell carcinoma (OCSCC) and larynx squamous cell carcinoma (LSCC). MATERIALS AND METHODS: Patients with OCSCC or LSCC were identified from datasets within The Cancer Genome Atlas. Somatic mutations and clinical information were included in the analysis. A Poisson regression model was used to evaluate the association of TMB with the primary cancer sites. RESULTS: We identified 5 datasets that included 396 OCSCC patients and 143 LSCC patients. Patients with LSCC had a significantly higher TMB than patients with OCSCC (crude risk ratio: 0.60, 95% confidence interval: 0.51-0.70, P < 0.001; adjusted risk ratio: 0.57, 95% confidence interval: 0.49-0.66, P < 0.001).Subgroup analyses suggested that this difference was independent of dataset, age, sex, race, alcohol drinking, smoking status, pathological risk, tumor grade, and tumor stage. Sensitivity analyses confirmed the robustness of this finding. CONCLUSION: To the best of our knowledge, this is the first study to identify a significant difference in TMB between OCSCC and LSCC. Though preliminary, these findings might have implications for guiding the development of trials for examining the response of head and neck carcinomas to immune checkpoint inhibitor treatments.

Association between NF-κB Activation in Peripheral Blood Mononuclear Cells and Late Skin and Subcutaneous Fibrosis following Radiotherapy.

BACKGROUND: This study aimed at evaluating the association between the speed of nuclear factor-kappa B (NF-κB) activation in peripheral blood mononuclear cells (PBMCs) and late skin and subcutaneous fibrosis in patients with head and neck squamous cell carcinoma (HNSCC) after radiotherapy. METHODS: The speed of NF-κB activation was represented by the nuclear p65 expression ratio before and after irradiation. The optimal time point to measure the ratio was determined by Western blot in the PBMCs from healthy outpatients ranging from 0 to 12 hours after ex vivo irradiation. We recruited patients with HNSCC who had received ratiotherapy and who were under regular follow-up care. We assessed the association between the risk of developing ≥grade 2 late fibrosis and the nuclear p65 expression ratio in the PBMCs after ex vivo irradiation in these patients. RESULTS: The maximum nuclear p65 ratio was observed at 1 hour after ex vivo irradiation in the PBMCs from the healthy outpatients. The speed of NF-κB activation was then represented by the nuclear p65 ratio in the PBMCs before and 1 hour after ex vivo irradiation. A total of 200 patients with HNSCC were recruited, 32.50% (n = 65) of which presented with ≥grade 2 late fibrosis. There was a significant association between the speed of NF-κB activation in the PBMCs and an increased risk of developing ≥grade 2 late fibrosis in these patients (P = 0.004). Subgroup analysis suggested that this finding was independent of the known clinical characteristics. CONCLUSIONS: The speed of NF-κB activation might be a potential predictor of late toxicity in cancer patients after radiotherapy. Prospective studies are needed for validation.

Impact of age on the overall survival benefits of anti-EGFR-containing regimens in head and neck squamous cell carcinoma: A meta-analysis of randomized controlled trials.

BACKGROUND: We conducted a meta-analysis to examine the associations of age, human papillomavirus (HPV) infection, and performance status with the overall survival (OS) benefits of patients with head and neck squamous cell carcinoma (HNSCC) after treatment with versus without epidermal growth factor receptor (EGFR) inhibitors. METHODS: We systematically searched literature for randomized controlled trials comparing chemotherapy or radiotherapy with versus without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCCs. Hazard ratios (HRs) for OS were calculated using random-effects models for patient groups according to age (younger vs. older), HPV infection status (p16-positive vs. p16-negative), and performance status score (better vs. poorer). RESULTS: Five phase III trials with 2653 patients were included. EGFR inhibition was associated with a greater OS benefit in younger patients than in older counterparts (HR 0.70 vs. 1.05, P < 0.001). There were no apparent differences in OS based on HPV status (P = 0.860) or performance status score (P = 0.235). Largely consistent results were obtained following stratification by treatment strategy (i.e., chemotherapy and radiotherapy). CONCLUSIONS: Patient age appears to impact OS independent of HPV infection and performance status after adding EGFR inhibitor agents during HNSCC treatment. This finding may help design relevant clinical trials.