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Radiotherapy Dose-Fractionation 2 The Royal College of Radiologists Board of Faculty of Clinical Oncology Radiotherapy Dose-Fractionation 2 The Royal College of Radiologists, a registered charity, exists to This document is designed to support, not dictate, decision advance the science and practice of Radiology and Oncology. making. Clinical practice is varied. Although guidance can, to some extent, encompass a part of this variation, there can be It produces standards documents to provide guidance to Clinical no set of guidelines that will deal with all possible eventualities. Oncologists and others involved in the delivery of cancer services This is where clinical judgement and guidelines complement each with the aim of defining good practice, advancing practice and other. Clinical practice is changing rapidly. Readers are referred improving services for the benefit of patients. back to the source literature to inform their clinical judgment. Radiotherapy Dose–Fractionation June 2006 The Royal College of Radiologists Board of Faculty of Clinical Oncology Radiotherapy Dose-Fractionation Contents 1 Dean’s foreword 4 2 Executive summary 5 3 Introduction 6 3.1 Background 6 3.2 Methodology 8 3.3 Fractionation in radiotherapy: A brief history 10 3.4 Fractionation and organs at risk (OAR) 14 3.5 Radiation therapy as a complex intervention 16 3.6 Radiotherapy planning and dose-prescription 20 4 Guidance on radiotherapy dose-fractionation 21 4.1 Anal cancer 21 4.2 Bladder cancer 23 4.3 Breast cancer 26 4.4 Central nervous system (CNS) malignancy 30 4.5 Gastro-oesophageal cancer 33 4.6 Gynaecological malignancy 37 4.7 Head and neck cancer 40 4.8 Lung cancer 43 4.9 Lymphoma 49 4.10 Paediatric cancer 53 4.11 Prostate cancer 54 4.12 Rectal cancer 58 4.13 Sarcoma 60 4.14 Seminoma 62 4.15 Bone metastases 64 4.16 Cerebral metastases 67 4.17 Spinal cord compression 70 5 Summary of recommendations 73 6 Planning for the future 76 7 Clinical audit, service development and research 80 8 Acknowledgements 82 1. Dean’s foreword It is with a strong feeling of privilege and pride that I write this introduction to our Dose-Fractionation document. Since the establishment of the Faculty of Clinical Oncology in 1992, we have published nearly 50 documents relating to many aspects of our professional lives, oncology service manage- ment and specific clinical problem areas. I have no compunction in stating that this one is the most important contribution that the Faculty as an entity has made to the practice of Radiotherapy in the UK during these last 15 years. It has also involved more Fellows and been subject to more open consultation than any previous document, and yet from inception to delivery this enormous project has taken only 18 months. So many of our Fellows have played an active part that it would dangerous for me to attempt to start identifying individuals but there is one exception to that principle. Michael Williams convinced me that the Officers’ dream of pulling together the evidence base for UK fractionation policies in a professional and non-confrontational way was achievable. He has, as many of you know, personally led the process very actively throughout, has harnessed the many disparate talents of our drafters and edited the document into a style that I think we can be very proud of. I do feel that I need to record the Faculty’s enormous debt to him in particular and to the members of the working 4 party and the contributors. I am also very excited for the Faculty because we are now going to publish the full document on the College website in a manner that allows each subspecialty chapter to be published individually, but in a standard RCR format. It is the intention of Officers that the individual site orientated chapters will become the responsibility of the Faculty’s new Site Orientated eNetworks (SOeNs) and that they will be stimulated to review their element of the advice annually. They will be able to modify, rework and republish their chapter(s) when it is agreed that it is professionally possible to support change. We are, therefore, taking our most important Faculty project and, utilising the new college IT resources, thrusting it into the electronic era for the benefit, we believe, of UK Radiotherapy and its present and future patients. Dr Robin Hunter Vice-President and Dean Faculty of Clinical Oncology June 2006 Radiotherapy Dose–Fractionation June 2006 2. Executive summary 2.1 One in three patients in the UK develops cancer during their lifetime, and 50% of these patients should receive radiotherapy treatment. The demand for radiotherapy is increasing at 3% per annum. 2.2 Surveys demonstrate variations in radiotherapy practice with some departments conforming to the international norm of curative treatment delivered over a 6–7 week period and others, at least in part due to historical resource constraint, delivering curative regimens of 3–4 weeks’ duration. 2.3 The Royal College of Radiologists (RCR) has therefore commissioned this report, in order to identify fractionation regimens for which there is high quality evidence for both safety and efficacy. 2.4 The report also identifies areas where further research is required to provide such evidence. 2.5 The report aims, where possible, to recommend evidence-based treatment regimen(s) for a given clinical situation and, where no such firm evidence exists, to present acceptable treatment options, ranked according to the level of evidence available. 5 2.6 It has only been possible to make ten Grade A recommendations for radical treatment and six for palliative treatment. 2.7 In many clinical situations, a state of equipoise exists, where the available published evidence is insufficient to favour one particular treatment regimen over another. We await the results of clinical trials to resolve these issues. 2.8 Where equipoise exists, and trial data are not available, clinicians should exercise considerable caution when considering changes in their treatment practice, based on the understandable desire to minimise resource utilisation. Radiotherapy is a complex intervention, and great harm can result from well-intentioned changes in practice, based solely on theory or an inadequate evidence base. Radiotherapy Dose–Fractionation June 2006 6 3. Introduction 3.1 Background 3.1.1 Radiotherapy fractionation in the UK differs from that in the rest of the world. Over the last 60 years, alternative radiotherapy fractionation regimens have been developed in the UK, at least in part to conserve resources. Shorter regimens using fewer fractions than North America and Europe are often used in radical treatment. This is based on extensive and well- documented clinical research particularly in Manchester and Edinburgh.1–5 In much of the USA and Europe fractions of 2 Gy or less are the standard of care.6 3.1.2 Clinical practice in the UK was surveyed in 1989.7 Clinicians were asked about the prescriptions which they would write for patients in six different cancer scenarios. A wide variety of dose-fractionation regimens was demonstrated and in only one of the six scenarios did more than 25% of clinical oncologists say they would prescribe the same treatment regimen. 3.1.3 An audit of radiotherapy practice in the UK in September 2003 showed that practice had become more uniform and closer to practice in North America and Europe over the last 15 years.8 However, there were significant variations in both radical and palliative treatment. For radical radiotherapy, 54% of prescriptions were for a fraction size of 1.8–2.0 Gy, but the distribution was bi-modal and 20% of patients were prescribed fraction sizes of 2.7–3.0 Gy.8 There were important differences in resource use for the treatment of common malignancies. 3.1.4 The Board of Faculty of Clinical Oncology therefore convened a working party in 2004 with the following terms of reference: • To develop a statement on evidence-based clinical practice from published peer-reviewed evidence. • To produce short consensus statements about the management of the major malignancies, including palliative treatment. • To define evidence-based radiotherapy regimens for each major malignancy. • To identify trials in progress which may have a major effect on practice. • To identify other significant areas for clinical trial. Radiotherapy Dose–Fractionation June 2006 3.1.5 The focus of this project was on linear accelerator use, and skin cancer was consequently excluded from consideration. In addition, rarer malignancies were excluded unless they had a particularly good evidence base, as the impact on resource use would be slight. 3.1.6 Brachytherapy may form part of the patient’s treatment but was not considered further in this project. References 1 Paterson R. The Treatment of Malignant Disease by Radiotherapy (2nd edn). London: Edward Arnold, 1963. 2 Hendry JH, Roberts SA, Slevin NJ, et al. Influence of radiotherapy treatment time on control of laryngeal cancer: Comparisons between centres in Manchester, UK and Toronto, Canada. Radiother Oncol 1994, 31:14–22. 3 Withers HR, Peters LJ, Taylor JM, et al. Local control of carcinoma of the tonsil by radiation therapy: An analysis of patterns of fractionation in nine institutions. Int J Radiat Oncol Biol Phys 1995, 33:549–562. 4 Withers HR, Peters LJ, Taylor JM, et al. Late normal tissue sequelae from radiation therapy for carcinoma of the tonsil: Patterns of fractionation study of radiobiology. Int J Radiat Oncol Biol Phys 1995, 33:563–568. 7 5 Gowda RV, Henk JM, Mais KL, et al. Three weeks radiotherapy for T1 glottic cancer: The Christie and Royal Marsden Hospital experience. Radiother Oncol 2003, 68:105–111. 6 Fletcher GH. Textbook of Radiotherapy. Philadelphia: Lea & Febiger, 1973.
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