Adjuvant management of locally advanced oral squamous cell carcinoma - real-world challenges and opportunities.

Patients with locally advanced oral squamous cell cancer (LAOSCC) are treated with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) following surgical ablation. This depends on the pathological risk factors and aims to reduce the risk of local recurrence and improve survival. Delivery of these aggressive treatments is, however, challenging particularly following major surgery. To inform the adaptations necessary to deliver gold-standard therapy, we aimed to describe real-world delivery of multimodality treatment in LAOSCC, in a UK population with high levels of disease incidence and low socioeconomic status. Patients with LAOSCC (T1-4 N1-3/T3-4 N0) who were treated between October 2014 and October 2016 and had a minimum follow up of 24 months were included. They were identified using the Somerset Cancer Register and data were collected through retrospective case note review. Approval was obtained from the audit departments at the relevant NHS institutions, and data were analysed using IBM SPSS Statistics for Windows version 24 (IBM Corp). The analysis included 129 patients with 82% having an initial performance status (PS) of 0-1. The most frequent change in PS was a one point drop (46%). Twenty of the 93 eligible patients (22%) underwent adjuvant CRT. A total of 37 (40%) began adjuvant CRT/RT within 42 days, and 79 (85%) within 56 days. A delay in initiating adjuvant therapy was associated with higher rates of complications and a longer postoperative hospital stay. Concordance between imaging and pathological nodal staging was poor (cK 0.223). PS frequently declines after complex surgical procedures and long postoperative recovery periods, leading to difficulties providing adjuvant treatments within the national guidance of 42 days. Frequent deviation from planned adjuvant therapies highlights the need for improved treatment strategies.

Estimation of compliance with exclusive smoking of very low nicotine content cigarettes using plasma cotinine.

Regulations requiring a reduction of the nicotine content in cigarettes to minimally addictive levels could significantly reduce the public health impact of cigarette smoking. Clinical trials evaluating this strategy are ongoing and methods have been developed to use nicotine biomarkers to estimate compliance with use of very low nicotine content cigarettes (VLNCs). To date, these methods have not considered the potential contribution of nicotine absorption from environmental tobacco smoke (ETS) among research participants. This study used data from 100 randomly selected study completers in ongoing clinical trials of VLNCs (50 randomized to Usual Nicotine Content Cigarettes (UNCs) and 50 to VLNCs) to assess the use of plasma cotinine to estimate compliance. Plasma cotinine and smoking behavior were recorded at baseline after 2 weeks smoking UNC cigarettes, and then after 18 weeks of either continuing smoking UNCs or reducing the nicotine content such that the last 6 weeks comprised smoking VLNCs. Plasma cotinine remained stable (267 ng/ml) in the UNC group but reduced to 93 ng/ml in the VLNC group (p < 0.01). Compliance with smoking VLNCs was first estimated by comparing the cotinine per cigarette on VLNCs with UNCs after allowing for potential compensatory smoking. We found that 29 (58%) of the VLNC group were compliant. Adjusting for potential ETS exposure estimated 32 (64%) to be compliant. This latter group (n = 32) had a mean plasma cotinine on VLNCs of 7 ng/ml (range = 3-16.4 ng/ml). Adjusting for potential ETS exposure may improve identification of participants who plausibly complied with exclusive VLNC use.

Nitric oxide synthase expression is downregulated in basal cell carcinoma of the head and neck.

The small molecule nitric oxide (NO) has many actions, most of which are poorly understood. Recently, NO and related compounds have been implicated in skin damage caused by ultraviolet light although their exact role is not clear. We undertook an immuno histochemical study to assess the expression of type II NO synthase (NOS2) and type III (NOS3) in basal cell carcinomas (BCCs) of the head and neck. In all 48 cases studied, NOS2 was found in the basal cell layer of the skin at the tumour margin but it w as significantly reduced in the tumour epithelial cells (P=0.001). NOS3 was localized to the endothelium of the blood vessels in both skin and tumour in all cases, and it was not seen in the tumour epithelial cells. The results suggest that expression of NOS is down-regulated in basal cell carcinomas.