Circulating tumor DNA (ctDNA) has been suggested as a surrogate biomarker for early detection of cancer recurrence. We aimed to explore the utility of ctDNA as a noninvasive prognostic biomarker in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. Seventy HNSCC specimens were analysed for the detection of TP53 genetic alterations utilizing next-generation sequencing (NGS). TP53 mutations were revealed in 55 (79%). Upon detection of a significant TP53 mutation, circulating cell-free DNA was scrutinized for the presence of the tumor-specific mutation. ctDNA was identified at a minimal allele frequency of 0.08% in 21 out of 30 processed plasma samples. Detectable ctDNA correlated with regional spread (N stage ≥ 1, p = 0.011) and poorer 5-year progression-free survival (20%, 95% CI 10.9 to 28.9, p = 0.034). The high-risk worst pattern of invasion (WPOI grade 4–5) and deep invasion were frequently found in patients whose ctDNA was detected (p = 0.087 and p = 0.072, respectively). Detecting mutated TP53 ctDNA was associated with poor progression-free survival and regional metastases, indicating its potential role as a prognostic biomarker. However, ctDNA detectability in early-stage disease and the mechanisms modulating its release into the bloodstream must be further elucidated.

Advanced cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with poor outcome despite multimodality therapy. Comprehensive risk stratification may pinpoint the most suitable adjuvant treatment. This study aimed to evaluate the outcomes of surgically treated locoregional CSCCHN and to identify prognostic indicators of treatment outcomes. We retrospectively analyzed disease variables, pathologic characteristics, and management in association with treatment outcomes of all consecutive advanced CSCCHN patients who underwent surgical resection at Tel Aviv Sourasky Medical Center. From 2008 to 2018, 74 patients met the inclusion criteria. Only perineural invasion (PNI) was significantly associated with worse overall survival (OS) (P = .001). Location within the facial “mask areas” was significantly associated with pathologically negative cervical disease (P = .001). Forty-seven patients underwent adjuvant radiation therapy (RT) which significantly improved OS and disease-free survival versus surgery alone (P = .025 and P = 0.035, respectively). PNI was associated with worse OS in surgically treated advanced CSCCHN. Adjuvant RT conferred better outcomes despite high risk features.

Background: The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for identifying patients at high risk of cSCC. This meta-analysis aimed to assess the prognostic significance of a 40-gene expression profile (40-GEP) both independently and integrated with clinicopathologic risk factors and established staging systems (American Joint Committee on Cancer, eighth edition (AJCC8) and Brigham and Women’s Hospital (BWH)). Methods: Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar, were systematically searched to identify cohort studies and randomized controlled trials on evaluations of the prediction value of 40-GEP in cSCC patients up to January 2023. The metastatic risk analysis of a given 40-GEP class combined with tumor stage and/or other clinicopathologic risk factors was based upon log hazard ratios (HRs) and their standard error (SE). Heterogeneity and subgroup analyses were performed, and data quality was assessed. Results: A total of 1019 patients from three cohort studies were included in this meta-analysis. The overall three-year metastatic-free survival rates were 92.4%, 78.9%, and 45.4% for class 1 (low risk), class 2A (Intermediate risk), and class 2B (high risk) 40-GEP, respectively, indicating a significant variation in survival rates between the risk classification groups. The pooled positive predictive value was significantly higher in class 2B when compared to AJCC8 or BWH. The subgroup analyses demonstrated significant superiority of integrating 40-GEP with clinicopathologic risk factors or AJCC8/BWH, especially for class 2B patients. Conclusions: The integration of 40-GEP with staging systems can improve the identification of cSCC patients at high risk of metastasis, potentially leading to improved care and outcomes, especially in the high-risk class 2B group.

Background Military aviators are potentially at risk for developing noise-induced hearing loss. Whether ambient aircraft noise exposure causes hearing deficit beyond the changes attributed to natural ageing is debated. The aim of this research was to assess changes in hearing thresholds of Israeli Air Force (IAF) pilots over 20 years of military service and identify potential risk factors for hearing loss. Methods A retrospective cohort analysis was conducted of pure-tone air conduction audiograms of pilots, from their recruitment at 18 years of age until the last documented medical check-up. Mean hearing thresholds were analysed in relation to age, total flight hours and aircraft platform. Comparisons were made to the hearing thresholds of air traffic controllers (ATCs) who were not exposed to the noise generated by aircraft while on duty. Results One hundred and sixty-three pilots were included, with flying platforms ranging from fighter jets (n=54), combat helicopters (n=27), transport helicopters (n=52) and transport aircraft (n=30). These were compared with the results from 17 ATCs. A marked notch in the frequency range of 4–6 kHz was demonstrated in the mean audiograms of all platforms pilots, progressing with ageing. Hearing threshold shifts in relation to measurements at recruitment were first noted at the age of 30 years, particularly at 4 kHz (mean shift of 2.97 dB, p=0.001). There was no statistical association between flying variables and hearing thresholds adjusted for age by logistic regression analysis. Conclusions The audiometric profile of IAF pilots has a pattern compatible with noise exposure, as reflected by characteristic noise notch. However, no flight variable was associated with deterioration of hearing thresholds, and no significant difference from non-flying controls (ATCs) was seen.

Objective: To determine the best timing for surgical intervention for adults with recurrent tonsillitis (RT).Methods: A Markov model was constructed using variables and ranges based upon a literature review. A 1‐way sensitivity analysis was performed to evaluate the number of yearly bouts at which each algorithm (antibiotics or tonsillectomy) would be favored. A Monte‐Carlo probabilistic sensitivity analysis was calculated for gains and cost. Model outcomes were measured with quality‐adjusted life‐years (QALYs) and incremental cost‐effectiveness ratios (ICER) for tonsillectomy versus repeat antibiotic treatment.Results: Patients expected to sustain a single annual tonsillitis event will have a negative QALY of 0.02 if treated with surgery and those with 2 annual events will have a QALY gain from undergoing tonsillectomy of 0.01, 3 events = 0.03, 4 events = 0.05, 5 events = 0.07, 6 events = 0.09, 7 events = 0.1, and 8 events = 0.11. These gains became meaningful only after 2 years of recurrent bouts. The average cost of tonsillectomy was 3,238 USD, and the overall average cost of RT was 7,069 USD (an incremental cost of 3,831 USD). The ICER of tonsillectomy over antibiotic treatment for 1 QALY gain was 44,741 USD.Conclusion: Adult patients who sustain more than 3 annual bouts of tonsillitis over a period of at least 2 years will gain QALY after tonsillectomy. These gains increase proportionally to the number of yearly events and perennial episodes. The incremental costs of tonsillectomy fail to meet the NICE guidelines but are within other acceptable reference ranges.Level of Evidence: NA Laryngoscope, 134:2153–2161, 2024