• 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.
    • Evaluation of larynx-sparing techniques with IMRT when treating the head and neck.

      Webster, Gareth J; Rowbottom, Carl G; Ho, Kean F; Slevin, Nicholas J; Mackay, Ranald I; North Western Medical Physics, Christie Hospital National Health Service Foundation Trust, Manchester, UK. Gareth.Webster@physics.cr.man.ac.uk (2008-10-01)
      PURPOSE: Concern exists that widespread implementation of whole-field intensity-modulated radiotherapy (IMRT) for the treatment of head-and-neck cancer has resulted in increased levels of dysphagia relative to those seen with conventional planning. Other investigators have suggested an alternative junctioned-IMRT (J-IMRT) method, which matches an IMRT plan to a centrally blocked neck field to restrict the laryngeal dose and reduce dysphagia. The effect on target coverage and sparing of organs at risk, including laryngeal sparing, in the optimization was evaluated and compared with that achieved using a J-IMRT technique. METHODS AND MATERIALS: A total of 13 oropharyngeal cancer whole-field IMRT plans were planned with and without including laryngeal sparing in the optimization. A comparison of the target coverage and sparing of organs at risk was made using the resulting dose-volume histograms and dose distribution. The nine plans with disease located superior to the level of the larynx were replanned using a series of J-IMRT techniques to compare the two laryngeal-sparing techniques. RESULTS: An average mean larynx dose of 29.1 Gy was achieved if disease did not extend to the level of the larynx, with 38.8 Gy for disease extending inferiorly and close to the larynx (reduced from 46.2 and 47.7 Gy, respectively, without laryngeal sparing). Additional laryngeal sparing could be achieved with J-IMRT (mean dose 24.4 Gy), although often at the expense of significantly reduced coverage of the target volume and with no improvement to other areas of the IMRT plan. CONCLUSION: The benefits of J-IMRT can be achieved with whole-field IMRT if laryngeal sparing is incorporated into the class solution. Inclusion of laryngeal sparing had no effect on other parameters in the plan.
    • IMRT dose fractionation for head and neck cancer: variation in current approaches will make standardisation difficult.

      Ho, Kean F; Fowler, Jack F; Sykes, Andrew J; Yap, Beng K; Lee, Lip W; Slevin, Nicholas J; Academic Department of Radiation Oncology, University of Manchester, Christie Hospital, Wilmslow Road, Manchester, UK. (2009)
      INTRODUCTION: Altered fractionation has demonstrated clinical benefits compared to the conventional 2 Gy/day standard of 70 Gy. When using synchronous chemotherapy, there is uncertainty about optimum fractionation. IMRT with its potential for Simultaneous Integrated Boost (SIB) adds further to this uncertainty. This survey will examine international practice of IMRT fractionation and suggest possible reasons for diversity in approach. MATERIAL AND METHODS: Fourteen international cancer centres were surveyed for IMRT dose/fractionation practised in each centre. RESULTS: Twelve different types of dose fractionation were reported. Conventional 70-72 Gy (daily 2 Gy/fraction) was used in 3/14 centres with concurrent chemotherapy while 11/14 centres used altered fractionation. Two centres used >1 schedule. Reported schedules and number of centres included 6 fractions/week DAHANCA regime (3), modest hypofractionation (< or =2.2 Gy/fraction) (3), dose-escalated hypofractionation (> or =2.3 Gy/fraction) (4), hyperfractionation (1), continuous acceleration (1) and concomitant boost (1). Reasons for dose fractionation variability include (i) dose escalation; (ii) total irradiated volume; (iii) number of target volumes; (iv) synchronous systemic treatment; (v) shorter overall treatment time; (vi) resources availability; (vii) longer time on treatment couch; (viii) variable GTV margins; (ix) confidence in treatment setup; (x) late tissue toxicity and (xi) use of lower neck anterior fields. CONCLUSIONS: This variability in IMRT fractionation makes any meaningful comparison of treatment results difficult. Some standardization is needed particularly for design of multi-centre randomized clinical trials.
    • A novel imaging technique for fusion of high-quality immobilised MR images of the head and neck with CT scans for radiotherapy target delineation.

      Webster, Gareth J; Kilgallon, J E; Ho, Kean F; Rowbottom, Carl G; Slevin, Nicholas J; Mackay, Ranald I; North Western Medical Physics, Christie Hospital NHS Foundation Trust, Manchester, UK. gareth.webster@physics.cr.man.ac.uk (2009-06)
      Uncertainty and inconsistency are observed in target volume delineation in the head and neck for radiotherapy treatment planning based only on CT imaging. Alternative modalities such as MRI have previously been incorporated into the delineation process to provide additional anatomical information. This work aims to improve on previous studies by combining good image quality with precise patient immobilisation in order to maintain patient position between scans. MR images were acquired using quadrature coils placed over the head and neck while the patient was immobilised in the treatment position using a five-point thermoplastic shell. The MR image and CT images were automatically fused in the Pinnacle treatment planning system using Syntegra software. Image quality, distortion and accuracy of the image registration using patient anatomy were evaluated. Image quality was found to be superior to that acquired using the body coil, while distortion was < 1.0 mm to a radius of 8.7 cm from the scan centre. Image registration accuracy was found to be 2.2 mm (+/- 0.9 mm) and < 3.0 degrees (n = 6). A novel MRI technique that combines good image quality with patient immobilization has been developed and is now in clinical use. The scan duration of approximately 15 min has been well tolerated by all patients.