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Perlikos F.,Sotiria General Hospital | Harrington K.J.,Institute of Cancer Research | Harrington K.J.,Head and Neck Unit | Syrigos K.N.,Oncology Unit GPP
Critical Reviews in Oncology/Hematology | Year: 2013

Lung cancer remains one of the most common and malignant cancers worldwide. It is most often diagnosed at late stages, when it has already presented local invasion and distal metastases. The basic stages of invasion and metastasis involve the detachment of tumor cells from the extracellular matrix, invasion of surrounding tissues and basal lamina, intravasation into the blood stream, survival and transport through the blood stream, migration, arrest and extravasation at a distal site and formation of a metastatic lesion. These steps require fundamental mechanisms such as angiogenesis, degradation of matrix barriers, disruption of cell-cell and cell-matrix adhesion and inducement of cellular motility. Genes that regulate functions like unlimited growth potential, survival, genomic instability, angiogenesis, epithelial to mesenchymal transition and apoptosis evasion, are involved in giving lung cancer tumors invasive and metastatic competence. Improving of understanding of the underlying molecular and cellular mechanisms remains an urgent and essential issue, in order to develop new more effective strategies in preventing and treating lung cancer. © 2013 Elsevier Ireland Ltd.

Roe J.W.G.,Head and Neck Unit | Roe J.W.G.,Institute of Cancer Research | Ashforth K.M.,Head and Neck Unit
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2011

Purpose of review: Oncological treatment outcomes in head and neck cancer suggest both acute and longer-term oropharyngeal dysphagia. Studies have been published exploring the potential to improve swallowing outcomes using more targeted treatment modalities such as intensity-modulated radiotherapy (IMRT) and through the introduction of swallowing exercises prior to treatment. In this article, we will explore the literature relating to prophylactic swallowing exercises for patients undergoing (chemo-)radiotherapy. Recent findings: Recent studies have attempted to evaluate the benefit of prophylactic, pretreatment swallowing exercises for patients undergoing (chemo-)radiotherapy. We identified three peer-reviewed published studies which present data on the potential benefit of exercise. Only one randomized control trial which includes multidimensional swallowing evaluation with instrumental measures has been published. Authors of all the reviewed studies agree that randomized control trials including baseline measures are required with longitudinal follow-up. Summary: More research is required to complement oncological clinical trials evaluating the impact of prophylactic exercise on swallowing outcome. Multidimensional swallowing evaluation including instrumental and patient-reported measures should be conducted pretreatment and longitudinally to develop the evidence base for intervention in patients undergoing organ-preserving treatment protocols. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Lyons A.J.,Head and Neck Unit | Crichton S.,Kings College London | Pezier T.,Head and Neck Unit
Oral Oncology | Year: 2013

Objectives Trismus frequently occurs as a consequence of radiotherapy or chemo-radiotherapy to the head and neck, with a loss of function that can reduce the overall quality of life. Radiation can trigger an intense fibrosis within the masticatory muscles and transforming growth factor beta 1 (TGF β1) is involved in this process. As in other tissues the degree of fibrosis may be related to a single nucleotide polymorphism; C-T at position -509 in the TGF β1 gene. Materials and methods Trismus was measured in 62 patients before and after radiotherapy or chemoradiotherapy, blood was taken for DNA extraction, and genotype analysis of the TGF β1 gene. Trismus was analysed against, patient age, sex, tumour site and stage, radiotherapy, and chemotherapy. Results and conclusions After radiotherapy or chemo-radiotherapy the reduction in mouth opening was shown to be significantly related to the presence of the T allele (p < 0.001), with patients homozygous the most likely to be severely affected. No other patient, tumour or treatment factors were significant. Hence the TGF β1 genotype is likely to be an important predictor of the degree of post radiotherapy or chemo-radiotherapy trismus. © 2013 Elsevier Ltd. All rights reserved.

Good J.S.,Head and Neck Unit | Harrington K.J.,Head and Neck Unit | Harrington K.J.,The Institute of Cancer Research
Clinical Oncology | Year: 2013

A comprehensive, mechanistic understanding of radiobiological phenomena that can be integrated within the broader context of cancer biology offers the prospect of transforming clinical practice in radiation oncology. In this review, we revisit the six established biological hallmarks of cancer and examine how they have provided insights into novel therapeutic strategies. In addition, we discuss the potential of two emerging hallmarks to continue to expand our understanding beyond the narrow confines of the traditional 5Rs of radiobiology. © 2013 The Royal College of Radiologists.

Scott-Brown M.,University of Oxford | Miah A.,Head and Neck Unit | Harrington K.,Head and Neck Unit | Harrington K.,Institute of Cancer Research | Nutting C.,Head and Neck Unit
Radiotherapy and Oncology | Year: 2010

Inverse planned Intensity modulated radiotherapy (IMRT) can minimize the dose to normal structures and therefore can reduce long-term radiotherapy-related morbidity and may improve patients' long-term quality of life. Despite overwhelming evidence that IMRT can reduce late functional deficits in patients with head and neck cancer, treated with radiotherapy, a review of the published literature produced conflicting results with regard to quality of life outcomes. Following a critical appraisal of the literature, reasons for the discrepant outcomes are proposed. © 2010 Elsevier Ireland Ltd. All rights reserved.

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