• Chemoradiotherapy for locally advanced pancreatic cancer: a radiotherapy dose escalation and organ motion study.

      Henry, Ann M; Ryder, W David J; Moore, Christopher J; Sherlock, David J; Geh, J I; Dunn, P; Price, Patricia M; Academic Department of Radiation Oncology, The University of Manchester, Department of Medical Statistics, Christie Hospital NHS Trust, Manchester, UK. (2008-09)
      AIMS: To determine the efficacy of radiation dose escalation and to examine organ motion during conformal radiotherapy for locally advanced pancreatic cancer. MATERIALS AND METHODS: Thirty-nine patients who were consecutively treated with chemoradiotherapy were studied. Fifteen patients, treated from 1993 to 1997, received 50 Gy in 20 fractions (group I). Twenty-four patients, treated from 1997 to 2003, received an escalated dose of 55 Gy in 25 fractions (group II). Intra-fraction pancreatic tumour motion was assessed in three patients using megavoltage movies during radiation delivery to track implanted radio-opaque markers. RESULTS: Improved survival rates were seen in latterly treated group II patients (P=0.083), who received escalated radiotherapy to smaller treatment volumes due to advances in verification. Worse toxicity effects (World Health Organization grade 3-4) were reported by some patients (<10%), but treatment compliance was similar in both groups, indicating equivalent tolerance. Substantial intra-fraction tumour displacement due to respiratory motion was observed: this was greatest in the superior/inferior (mean=6.6 mm) and anterior/posterior (mean=4.75 mm) directions. Lateral displacements were small (<2 mm). CONCLUSIONS: Dose escalation is feasible in pancreatic cancer, particularly when combined with a reduction in irradiated volume, and enhanced efficacy is indicated. Large, globally applied margins to compensate for pancreatic tumour motion during radiotherapy may be inappropriate. Strategies to reduce respiratory motion, and/or the application of image-guided techniques that incorporate individual patients' respiratory motion into radiotherapy planning and delivery, will probably improve pancreatic radiotherapy.
    • 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.