TORPEdO: A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer.

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.

Voice burden in teachers and non-teachers in a UK population: A questionnaire-based survey.

Objective: To characterise the burden of voice disorders in teachers in a UK population, compare it with non-teachers and identify groups of teachers who may be particularly at risk of developing a voice problem.

Design: Questionnaire-based survey of primary and secondary school teachers and non-teachers. Questions consisted of general demographics, VHI-10 and questions relating to voice problems.

Pre-treatment tumour perfusion parameters and initial RECIST response do not predict long-term survival outcomes for patients with head and neck squamous cell carcinoma treated with induction chemotherapy.

Objectives: Previously, we showed that pre-treatment tumour plasma perfusion (Fp) predicts RECIST response to induction chemotherapy (ICT) in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The aim here was to determine whether the pre-treatment tumour Fp estimate, changes in tumour Fp or RECIST response post 2 cycles of ICT were prognostic for long-term survival outcomes.

Methods: A prospective study enrolled patients with high stage HNSCC treated with docetaxel (T), cisplatin (P) and 5-fluorouracil (F) (ICT) followed by synchronous cisplatin and intensity modulated radiotherapy.

Taxane, platinum and 5-FU prior to chemoradiotherapy benefits patients with stage IV neck node-positive head and neck cancer and a good performance status.

Purpose: The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most.

Methods: A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT.

Role of 18-Fludeoxyglucose positron emission tomography-computed tomography and subsequent panendoscopy in head and neck squamous cell carcinoma of unknown primary.

Objectives/hypothesis: Head and neck squamous cell carcinomas of unknown primary (HNSCCUP) accounts for up to 10% of presenting head and neck squamous cell carcinomas. Identification of the primary site allows for directed therapy. Where initial investigations have failed to locate the primary site, 18-fludeoxyglucose positron emission tomography-computed tomography (PET/CT) has emerged as a useful tool with improved sensitivity over positron emission tomography alone.

Tumor plasma flow determined by dynamic contrast-enhanced MRI predicts response to induction chemotherapy in head and neck cancer.

Objectives: Non-response to induction chemotherapy (IC) occurs in 30% of head and neck squamous cell carcinoma (HNSCC) and has been predicted by tumor plasma flow (Fp) derived by perfusion computed tomography. The present study was designed to test whether baseline tumor Fp determined by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) would predict IC response.

Materials And Methods: A prospective open study powered to test the relationship between tumor Fp and response to IC (docetaxel, cisplatin, 5-fluorouracil) enrolled 50 patients with stage IV HNSCC.

Prognostic value of hypoxia-associated markers in advanced larynx and hypopharynx squamous cell carcinoma.

Objectives/hypothesis: To determine the prognostic value of hypoxia-associated markers carbonic anhydrase-9 (CA-9) and hypoxia-inducible factor-1α (HIF-1α) in advanced larynx and hypopharynx squamous cell carcinoma (SCCa) treated by organ preservation strategies.

Study Design: Retrospective cohort study.

Methods: Pretreatment CA-9 and HIF-1α expression, clinicopathologic data, and tumor volume were analyzed in a series of 114 patients with T3-4 SCCa larynx or hypopharynx treated by (chemo)radiation.

Dynamic contrast-enhanced magnetic resonance imaging biomarkers in head and neck cancer: potential to guide treatment? A systematic review.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) generates microvascular parameters from the tracer kinetic analysis of a series of MRI images obtained in under 15 min. DCE-MRI parameters are associated with tumour hypoxia, which is well-established as a cause of treatment failure in head and neck squamous cell carcinoma (HNSCC). A systematic review was conducted of prospective DCE-MRI parameter studies in HNSCC in the English language literature.

A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer.

Purpose: Tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome, and hypoxic status predicts benefit from treatment. Yet, there is no universal measure of clinical hypoxia. The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types.

Molecular and cellular processes underlying the hallmarks of head and neck cancer.

The hallmarks of cancer were updated by Hanahan and Weinberg in 2011. Here we discuss the updated hallmarks in relation to what is known of the molecular and cellular processes underlying the development of head and neck squamous cell carcinoma (HNSCC). Several mechanisms are described, and recent surveys of HNSCC suggest a limited number of mutations, from which more mechanisms may emerge.

Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma.

Background And Purpose: Tumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours.

Materials And Methods: Tumour samples (n=201) from 80 HNSCC patients were collected prospectively from two centres.

Perfusion estimated with rapid dynamic contrast-enhanced magnetic resonance imaging correlates inversely with vascular endothelial growth factor expression and pimonidazole staining in head-and-neck cancer: a pilot study.

Purpose: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck.

Methods And Materials: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.

Mucosal melanoma of the head and neck: radiotherapy or surgery?

Introduction: Head and neck mucosal melanoma (MuM) is rare, comprising < 1% of all melanomas in Western Europe.

Methods: A retrospective analysis of case records of patients treated between 1965 and 2001 was carried out. (Survival outcomes were obtained from the case notes and cancer registry.

Effect of temporal bone resection on temporomandibular joint function: a quality of life study.

Objectives: Temporal bone resection for carcinoma may affect quality of life (QOL) and result in temporomandibular joint (TMJ) disorders. The aims of this study were to 1) assess TMJ function after temporal bone resection, and 2) assess the impact of TMJ dysfunction on QOL.

Study Design: Chart and patient review and QOL study.

Exon array analysis of head and neck cancers identifies a hypoxia related splice variant of LAMA3 associated with a poor prognosis.

The identification of alternatively spliced transcript variants specific to particular biological processes in tumours should increase our understanding of cancer. Hypoxia is an important factor in cancer biology, and associated splice variants may present new markers to help with planning treatment. A method was developed to analyse alternative splicing in exon array data, using probeset multiplicity to identify genes with changes in expression across their loci, and a combination of the splicing index and a new metric based on the variation of reliability weighted fold changes to detect changes in the splicing patterns.

Potential risk factors associated with the use of cidofovir to treat benign human papillomavirus-related disease.

Background: Cidofovir is currently being used off-licence to treat different viral infections, such as benign low-risk human papillomavirus (HPV)-related recurrent respiratory papillomatosis (RRP). There are concerns over the safety of this practice as rat studies demonstrated a high malignant transformation rate. As yet, there are no clinical reports of cidofovir-induced malignant changes in humans.

Shoulder morbidity after pectoralis major flap reconstruction for head and neck cancer.

Background: The effect of pectoralis major flap (PMF) harvest on shoulder function, allowing for the effects of neck dissection, has not previously been objectively measured.

Methods: Twenty-two patients who underwent PMF reconstruction were studied. The control group comprised 35 patients with neck dissection (without PMF).

Cidofovir induces an increase in levels of low-risk and high-risk HPV E6.

Background: Cidofovir is a nucleoside analogue that is used off-license to treat recurrent respiratory papillomatosis (RRP) caused by HPV6/11. However, the effect of this drug upon low-risk HPV 6/11 gene expression is unknown.

Methods: The expression of E6 was evaluated by RT-PCR in HPV-ve C33A cervical carcinoma cells stably transfected with both low- and high-risk HPV E6 cDNA's and in SiHa (HPV16+ve) cervical carcinoma cells after treatment with 2 doses and durations of exposure to cidofovir.

Audit of clinical coding of major head and neck operations.

Introduction: Within the NHS, operations are coded using the Office of Population Censuses and Surveys (OPCS) classification system. These codes, together with diagnostic codes, are used to generate Healthcare Resource Group (HRG) codes, which correlate to a payment bracket. The aim of this study was to determine whether allocated procedure codes for major head and neck operations were correct and reflective of the work undertaken.

The impact of radiotherapy on swallowing and speech in patients who undergo total laryngectomy.

Objectives: Quality of life studies have shown no detrimental effect with radiotherapy (RT) in patients who have a total laryngectomy. We wished to determine the effect of RT (initial or postoperative) specifically on the swallowing and voice function in patients treated by total laryngectomy (TL) for carcinoma of the larynx.

Design: Multicenter chart review.