• Epidermal growth factor receptor-targeted therapy.

      West, Catharine M L; Joseph, L; Bhana, Sara; Academic Radiation Oncology, The University of Manchester, Christie Hospital, Manchester M20 4BX, UK. catharine.west@manchester.ac.uk (2008-10)
      High epidermal growth factor receptor (EGFR) expression is a feature of human tumours and is an adverse prognostic factor for radiotherapy outcome. High expression is associated with benefit from accelerated radiotherapy in patients with head and neck squamous cell carcinoma. Anti-EGFR strategies potentiate the effects of radiotherapy and the inhibition of deoxyribonucleic acid repair appears to be important amongst a wide range of mechanisms, which include effects on angiogenesis, differentiation and the immunological response. There is considerable interest in exploring combined modality therapies involving radiation and EGFR antagonists for the curative treatment of cancer patients. Important issues in designing new trials are to investigate optimal scheduling and to establish biobanks to develop biomarkers for future patient selection.
    • Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples.

      Hall, J S; Leong, Hui Sun; Armenoult, L S C; Newton, G E; Valentine, Helen R; Irlam, Joely J; Möller-Levet, Carla S; Sikand, Kanwal A; Pepper, Stuart D; Miller, Crispin J; et al. (2011-03-15)
      Degradation and chemical modification of RNA in formalin-fixed paraffin-embedded (FFPE) samples hamper their use in expression profiling studies. This study aimed to show that useful information can be obtained by Exon-array profiling archival FFPE tumour samples.
    • Monitoring dosimetric impact of weight loss with kilovoltage (kV) cone beam CT (CBCT) during parotid-sparing IMRT and concurrent chemotherapy.

      Ho, Kean F; Marchant, Thomas E; Moore, Christopher J; Webster, Gareth J; Rowbottom, Carl G; Pennington, Hazel; Lee, Lip W; Yap, Beng K; Sykes, Andrew J; Slevin, Nicholas J; et al. (2012-03-01)
      Parotid-sparing head-and-neck intensity-modulated radiotherapy (IMRT) can reduce long-term xerostomia. However, patients frequently experience weight loss and tumor shrinkage during treatment. We evaluate the use of kilovoltage (kV) cone beam computed tomography (CBCT) for dose monitoring and examine if the dosimetric impact of such changes on the parotid and critical neural structures warrants replanning during treatment.
    • Preliminary study of oxygen-enhanced longitudinal relaxation in MRI: a potential novel biomarker of oxygenation changes in solid tumors.

      O'Connor, James P B; Naish, Josephine H; Parker, Geoff J M; Waterton, John C; Watson, Yvonne; Jayson, Gordon C; Buonaccorsi, Giovanni A; Cheung, Susan; Buckley, David L; McGrath, Deirdre M; et al. (2009-11-15)
      PURPOSE: There is considerable interest in developing non-invasive methods of mapping tumor hypoxia. Changes in tissue oxygen concentration produce proportional changes in the magnetic resonance imaging (MRI) longitudinal relaxation rate (R(1)). This technique has been used previously to evaluate oxygen delivery to healthy tissues and is distinct from blood oxygenation level-dependent (BOLD) imaging. Here we report application of this method to detect alteration in tumor oxygenation status. METHODS AND MATERIALS: Ten patients with advanced cancer of the abdomen and pelvis underwent serial measurement of tumor R(1) while breathing medical air (21% oxygen) followed by 100% oxygen (oxygen-enhanced MRI). Gadolinium-based dynamic contrast-enhanced MRI was then performed to compare the spatial distribution of perfusion with that of oxygen-induced DeltaR(1). RESULTS: DeltaR(1) showed significant increases of 0.021 to 0.058 s(-1) in eight patients with either locally recurrent tumor from cervical and hepatocellular carcinomas or metastases from ovarian and colorectal carcinomas. In general, there was congruency between perfusion and oxygen concentration. However, regional mismatch was observed in some tumor cores. Here, moderate gadolinium uptake (consistent with moderate perfusion) was associated with low area under the DeltaR(1) curve (consistent with minimal increase in oxygen concentration). CONCLUSIONS: These results provide evidence that oxygen-enhanced longitudinal relaxation can monitor changes in tumor oxygen concentration. The technique shows promise in identifying hypoxic regions within tumors and may enable spatial mapping of change in tumor oxygen concentration.
    • Use of multiple biological markers in radiotherapy-treated head and neck cancer.

      Silva, Priyamal; Slevin, Nicholas J; Sloan, Philip; Valentine, Helen R; Ryder, W David J; Price, Patricia M; West, Catharine M L; Homer, Jarrod J; School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK. (2010-06)
      OBJECTIVE: Management of patients with head and neck squamous cell carcinoma is often based on clinical parameters, with little appreciation of the underlying tumour biology. Single biological marker studies fail to acknowledge the complexity of these tumours. Our aim was to define a profile of biological markers associated with outcome. DESIGN: This retrospective study involved consecutive patients with oropharyngeal squamous cell carcinoma treated with primary radiotherapy between 1996 and 2001. Pre-treatment biopsies were used to study the immunohistochemical expression of nine biological markers. Markers were chosen to reflect biologically relevant pathways. RESULTS: Following analysis of nine markers, a profile of two markers was derived (carbonic anhydrase 9 and major vault protein), the co-expression of which conferred a significantly poor probability of locoregional control. The prognostic effect of these biomarkers in combination was greater than their effect individually. CONCLUSION: Biomarker profiles can be established which highlight large differences in locoregional control. Identifying tumours that express both carbonic anhydrase 9 and major vault protein may facilitate patient selection for more aggressive treatment.