Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery.

BACKGROUND: Oral cavity is the most prevalent site of head and neck squamous cell carcinomas (HNSCCs). Most often diagnosed at a locally advanced stage, treatment is multimodal with surgery as the cornerstone. The aim of this study was to explore the molecular landscape of a homogenous cohort of oral cavity squamous cell carcinomas (OCSCCs), and to assess the prognostic value of tumor mutational burden (TMB), along with classical molecular and clinical parameters. PATIENTS AND METHODS: One hundred and fifty-one consecutive patients with OCSCC treated with upfront surgery at the Institut Curie were analyzed. Sequencing of tumor DNA from frozen specimens was carried out using an in-house targeted next-generation sequencing panel (571 genes). The impact of molecular alterations and TMB on disease-free survival (DFS) and overall survival (OS) was evaluated in univariate and multivariate analyses. RESULTS: Pathological tumor stage, extranodal spread, vascular emboli, and perineural invasion were associated with both DFS and OS. TP53 was the most mutated gene (71%). Other frequent molecular alterations included the TERT promoter (50%), CDKN2A (25%), FAT1 (17%), PIK3CA (14%), and NOTCH1 (15%) genes. Transforming growth factor-ß pathway alterations (4%) were associated with poor OS (P = 0.01) and DFS (P = 0.02) in univariate and multivariate analyses. High TMB was associated with prolonged OS (P = 0.01 and P = 0.02, in the highest 10% and 20% TMB values, respectively), but not with DFS. Correlation of TMB with OS remained significant in multivariate analysis (P = 0.01 and P = 0.005 in the highest 10% and 20% TMB values, respectively). Pathological tumor stage combined with high TMB was associated with good prognosis. CONCLUSION: Our results suggest that a high TMB is associated with a favorable prognosis in patients with OCSCC treated with upfront surgery.

Management of incidental discovery of microscopic squamous cell carcinoma in zones of osteoradionecrosis of the mandible.

OBJECTIVES: Osteoradionecrosis (ORN) of the mandible is a common complication of head and neck radiotherapy and often requires surgical treatment. Squamous cell carcinoma (SCC) can be exceptionally discovered within zones of ORN on histological examination of the operative specimen. The authors discuss the management of these lesions based on a short patient series. MATERIALS AND METHODS: This single-centre retrospective study was based on patients managed between 2012 and 2014 for ORN with incidental discovery of microscopic SCC. RESULTS: Five patients with incidental discovery of microscopic SCC in a zone of ORN of the mandible were included in this study. The mean time to onset of ORN after the end of radiotherapy for locally advanced SCC of the oral cavity or oropharynx was 42 months. Surgical treatment consisted of marginal or segmental mandibulectomy with free flap reconstruction. No recurrence was observed with a mean follow-up of 35 months [24-46]. CONCLUSION: The incidental discovery of microscopic SCC in a zone of ORN of the mandible is a rare event and has not been reported in the literature. Optimal management cannot be reliably defined due to the lack of data in the literature, but the present study supports careful histological examination of ORN specimens. Treatment must be as conservative as possible to avoid excessively invasive surgery.

Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival.

BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes. RESULTS: A median of 2 (range: 0-10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis. CONCLUSION: These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.

Peak inspiratory flow as predictor for tracheotomy.

OBJECTIVES: Quantitative evaluation of upper airway obstruction cannot be commonly performed under acute dyspnea, especially in head and neck cancer (HNC); the decision whether or not to perform airway control surgery may be difficult to reach. Peak inspiratory flow (PIF) has been previously demonstrated to be a useful tool to decide on decannulation after HNC surgery. The aim of the present study was to assess the role of PIF as a standardized non-invasive tool in quantifying severe inspiratory dyspnea requiring emergency tracheostomy. MATERIALS AND METHODS: A single-center prospective observational pilot study analyzed PIF measurements in 22 patients exhibiting acute dyspnea due to upper airway obstruction. MAIN OUTCOME MEASURES: The decision whether or not to perform tracheotomy was taken prior to PIF measurement. PIF was measured with a hand-held PIF meter (In-Check method), and laryngeal fiberoscopy was then performed. Obstruction severity was defined by PIF values. RESULTS: PIF could be measured prior to tracheotomy (imminent in 21 cases, postponed in 1) in all cases. PIF values below 53.1 L/min (i.e., 18.3% of theoretic value) correlated with necessity for emergency tracheotomy. This threshold is concordant with that previously found for the feasibility of decannulation (60L/min). CONCLUSIONS: PIF is a non-invasive quantitative parameter assessing severity of upper airway obstruction, that may be helpful in decision-making for tracheostomy. Testing is simple, quick and reproducible.

How to release neck dissections: Role of the triangle between the spinal accessory nerve and the internal jugular vein.

The neck dissection technique has been precisely defined. It allows resection of lymph node groups, comprising at least groups IIA, IIB, III and IV according to Robbins' classification for head and neck cancer. Neck dissection is classically performed in an upwards and forwards direction, but the technique can vary according to the site of lymph nodes. The authors describe the central role of dissection of the triangle between the spinal accessory nerve and the internal jugular vein at the beginning of neck dissection in order to facilitate group IIB dissection while avoiding traction on the spinal accessory nerve and to ensure early control of the internal jugular vein superiorly; release of the vein also facilitates subsequent dissection of the thyrolinguofacial trunk and identification of the hypoglossal nerve. This specific dissection and its role has not been previously described in the literature. This triangle constitutes the posterior part of group IIA, but is intimately related anatomically to group IIB dissection.