Association of quality of life with mortality in patients with adenoid cystic carcinoma using an internationally-validated QoL questionnaire (EQ-5D-5L).

Background/objectives: An evaluation of quality of life (QoL) is increasingly required for approval and reimbursement of new drug therapies. To support the evaluation of the impact of new drug therapies on QoL in single-arm studies in adenoid cystic carcinoma (ACC), we sought to determine the QoL baseline in a cohort of patients with ACC during routine follow up visits and to assess for associations with clinical or prognostic factors.

Methods: An internationally-validated QoL questionnaire (EQ-5D-5L) was completed by patients with ACC referred to an experimental medicine centre.

KDM6A, ARID1A and SETD2 loss-of-function mutations as prognostic biomarkers and their association with sites of metastatic progression in locally-advanced, recurrent or metastatic adenoid cystic carcinoma.

Objectives: Recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) is typically slow growing however, some patients have more rapid progression. We sought to classify mutations in chromatin regulating genes in ACC to determine the impact of chromatin regulatory disfunction on clinical outcomes.

Materials And Methods: Matched clinical-genomic data from 271 pts with non-resectable or R/M ACC were included in this study.

The Clinical Utilisation and Duration of Treatment with HER2-Directed Therapies in HER2-Positive Recurrent or Metastatic Salivary Gland Cancers.

Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC.

Diffuse scalp neurofibromas: Case series and Clinicoradiological characteristics of a rare vascular lesion.

Diffuse neurofibroma of the head and neck are rare tumours which have unique clinical and radiological findings. Presurgical diagnosis is important as these lesions are usually highly vascular and pre-operative embolisation can reduce the risk of intra-operative haemorrhage. In this article we describe four cases; two which underwent pre-operative embolisation, which should aid the reader in successfully diagnosing this entity before biopsy/surgery.

Randomized Phase 3 Trial of the Hypoxia Modifier Nimorazole Added to Radiation Therapy With Benefit Assessed in Hypoxic Head and Neck Cancers Determined Using a Gene Signature (NIMRAD).

Purpose: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT).

Methods And Materials: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689).

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.

Evaluation of the Clinical Utility of Genomic Profiling to Inform Selection of Clinical Trial Therapy in Salivary Gland Cancer.

For most patients with salivary gland cancer, there are no effective standard systemic therapies. Although clinical trials of biomarker-led drug therapies have delivered significant recent advances, there remains a need to understand the clinical utility of genomic profiling of cancer as a means to match patients with recurrent or metastatic salivary gland cancer to clinical trial therapies. In total, 209 patients with salivary gland cancers were profiled with 24 gene (n = 209)) and >325 gene (n = 32) DNA-based next-generation sequencing panels.

The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma.

Objectives: Despite wide excision and post-operative irradiation, loco-regional and/or metastatic recurrence is a significant clinical problem in salivary adenoid cystic carcinoma (SACC). Reliable biomarkers are required to tailor post-treatment surveillance to patients at highest risk of recurrence. We sought to determine the utility of TP53 and PIK3CA mutations as prognostic biomarkers in SACC.

Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.

Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (∆R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen.

FGFR2, HER2 and cMet in gastric adenocarcinoma: detection, prognostic significance and assessment of downstream pathway activation.

Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma.

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.

An in vivo hypoxia metagene identifies the novel hypoxia inducible factor target gene SLCO1B3.

A hypoxia-associated gene signature (metagene) was previously derived via in vivo data-mining. In this study, we aimed to investigate whether this approach could identify novel hypoxia regulated genes. From an initial list of nine genes, three were selected for further study (BCAR1, IGF2BP2 and SLCO1B3).

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.

Spectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma.

Purpose: To identify functionally related prognostic gene sets for head and neck squamous cell carcinoma (HNSCC) by unsupervised statistical analysis of microarray data.

Patients And Methods: Microarray analysis was performed on 14 normal oral epithelium and 71 HNSCCs from patients with outcome data. Spectral clustering (SC) analysis of the data set identified multiple vectors representing distinct aspects of gene expression heterogeneity between samples.

hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer.

Background: Hypoxia is an important mechanism of treatment resistance in head and neck squamous cell carcinoma (HNSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The authors have investigated the role of 3 microRNAs, including the hypoxia-induced hsa-miR-210, as potential markers of hypoxia or prognosis.

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.