E-8. Evidence-based palliative radiotherapy

Abstract

Evidence-based medicine has been defined as “the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients” [l]. It relies on quality evidence from well-conducted randomized control trials, and systematic reviews, including (but not confined to) meta-analyses. These reviews frequently result in practice guidelines, defined as “... systematically developed statements to assist provider and patient decisions about appropriate health care for specific clinical circumstances...” [2]. Systematic reviews and evidence based practice guidelines can then be used by health care providers, patients and decision makers (at an institutional or local national level), to achieve a wide range of goals, including provide most effective treatment, improve patient outcome, improve quality of care, minimize practice variations, decrease health care costs by minimizing ineffective treatment, yet still allow for physician autonomy and patients choice. Palliative Radiotherapy for lung cancer (specifically non-small cell lung cancer) is a topic that has been subject to numerous randomized controlled trials, comparing different palliative RT fractionation schemes (summarized in a Cochrane systematic review [3]), immediate vs delayed palliative radiation for asymptomatic patients [4] and palliative radiation +/chemotherapy [5]. Many, but not all, studies comparing different palliative RT regimens have suggested that less protracted radiation protocols provide better palliation, i.e. equivalent symptom control with less toxicity and less burden to the patient and family. Using shorter treatment protocols, approximately 80-85% of patients report improvement in hemoptysis, and 60% improvement in cough; pain improved in 2/3 patients. On average, symptom relief lasted for 50% or more of the patient’s survival time. No dose-fractionation schedule has to date demonstrated a clear superiority in terms of palliation, and until mid-nineties, there was no survival advantage to any of the regimens either. More recently, several studies have demonstrated prolonged survival in the higher dose palliative RT arm of the study: in the MRC trial [6] that difference was seen when comparing 36 Gy/13 fractions to 17 Gy/2 fractions; in the NCIC CTG trial [7] that was seen in patients treated with 20 Gy/5 fractions, as compared to single 10 Gy. This benefit appeared confined to the good performance status patients or those with localized disease (but who were not deemed candidates for aggressive treatment). The main challenge remains how to define and analyze symptom palliation in lung cancer, as a standard definition of palliation is lacking. The degree of improvement in symptoms present at baseline can be used as an index of palliation. However, the effectiveness of palliative radiation may be related to the initial severity of the symptom, not all the patients will have the symptom being assessed, and the timing of response may vary. A broader definition of palliative benefit of treatment would also include stability of mild symptoms and prevention of new symptoms. A method to calculate the palliative benefit of treatment using this broader definition has been described [8], which offers promise as a tool to better assess the benefit of a treatment in the setting where multiple symptoms are common, as is the case in lung cancer. Advances in practising evidence-based palliative radiotherapy will stem from a more uniform approach to analyzing palliation, an emphasis on both the quality of trials and of reporting of those trials [9]; creation and dissemination of systematic reviews and practice guidelines [IO], and attention to factors other than level of evidence which influence medical decisions, including values and beliefs of health care providers and patients, context of the decision and economic studies of impact of intervention, among others.