• 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.
    • 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.
    • Implementing image-guided radiotherapy in the UK: plans for a co-ordinated UK research and development strategy.

      Price, Patricia M; Heap, Gillian; Academic Clinical Oncology and Radiobiology Research Network, c/o Christie Hospital NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. (2008-05)
    • The radiobiology/radiation protection interface in healthcare.

      Martin, C J; Sutton, D G; West, Catharine M L; Wright, Eric G; Department of Clinical Physics and Bio-engineering, Gartnavel Royal Hospital, Glasgow, UK. (2009-06)
      The current knowledge of radiation effects is reviewed and implications for its application in healthcare considered. The 21st L H Gray conference gathered leading experts in radiobiology, radiation epidemiology, radiation effect modelling, and the application of radiation in medicine to provide an overview of the subject. The latest radiobiology research in non-targeted effects such as genomic instability and the bystander effect challenge the old models, but the implications for health effects on humans are uncertain. Adaptive responses to external stresses, of which radiation is one, have been demonstrated in cells and animal models, but it is not known how these might modify human dose-effect relationships. Epidemiological evidence from the Japanese A-bomb survivors provides strong evidence that there is a linear relationship between the excess risk of cancer and organ dose that extends from about 50 mSv up to 2.5 Sv, and results from pooled data for multiple epidemiological studies indicate that risks extend down to doses of 20 mSv. Thus linear extrapolation of the A-bomb dose-effect data provides an appropriate basis for radiological protection standards at the present time. Risks from higher dose diagnostic procedures fall within the range in which health effects can be demonstrated. There is therefore reason for concern about the rise in the number of computed tomography (CT) scans performed in many countries, and in particular the use of CT for screening of asymptomatic individuals. New radiotherapy techniques allow high dose radiation fields to be conformed more effectively to target volumes, and reduce doses to critical organs, but they tend to give a higher and more uniform dose to the whole body which may increase the risk of second cancer. It is important that radiation protection practitioners keep abreast of developments in understanding of radiation effects and advise the medical community about the implications of fundamental research when planning medical applications for the future.
    • Ultrasound Imaging to Assess Inter- and Intra-fraction Motion during Bladder Radiotherapy and its Potential as a Verification Tool.

      McBain, Catherine A; Green, M M; Stratford, Julia; Davies, Julie; McCarthy, Claire; Taylor, Benjamin; McHugh, D; Swindell, Ric; Khoo, Vincent S; Price, Patricia M; et al. (2009-06)
      AIMS: Organ motion is the principle source of error in bladder cancer radiotherapy. The aim of this study was to evaluate ultrasound bladder volume measurement as a surrogate measure of organ motion during radiotherapy: (1) to assess inter- and intra-fraction bladder variation and (2) as a potential treatment verification tool. MATERIALS AND METHODS: Twenty patients receiving radical radiotherapy for bladder cancer underwent post-void ultrasound bladder volume measurement at the time of radiotherapy treatment planning (RTP), and immediately before (post-void) and after receiving daily fractions. RESULTS: Ultrasound bladder volume measurement was found to be a simple and acceptable method to estimate relative bladder volume changes. Six patients showed significant changes to post-void bladder volume over the treatment course (P<0.05). The mean inter-fraction post-void bladder volume of five patients exceeded their RTP ultrasound bladder volume by more than 50%. Intra-fraction bladder volume increased on 275/308 (89%) assessed fractions, with the mean intra-fraction volume increases of seven patients exceeding their RTP ultrasound bladder volume by more than 50%. CONCLUSIONS: Both day-to-day bladder volume variation and bladder filling during treatment should be considered in RTP and delivery. Ultrasound may provide a practical daily verification tool by: supporting volume limitation as a method of treatment margin reduction; allowing detection of patients who may require interventions to promote bladder reproducibility; and identifying patients with prominent volume changes for the selective application of more advanced adaptive/image-guided radiotherapy techniques.