The Royal Marsden Dietary intervention for the prevention of toxicity during radiotherapy for pelvic cancer Clare Shaw, Dietitian ClareConsultant Shaw, CDietitian Linda Wedlake, Research Linda Wedlake, Research Dietitian Lorraine Watson, Macmillan Dietitian in Pelvic Radiation Disease Disease The Royal Marsden Acute GI-related toxicity Change in bowel habit: 90% Uncomfortable gas: 65% Need anti-diarrhoeals: 40% Faecal incontinence: 37% Henry J. Binder, Text book of Physiology Khalid U, IJROBP 2006 The Royal Marsden Acute radiation injury  Cytocidal effects: clonogenic and apoptotic cell death  Functional: non-cytocidal effects  Secondary effects: reactive and downstream cellular or tissue phenomena Hauer-Jensen et al 2007 COSPC 1:23-29 Hovdenak et al 2000 IJROBP 48:1111-7 The Royal Marsden Donowitz, 2012 Gastroenterolgy The Royal Marsden Benefits of dietary intervention in acute setting  Reduce acute reaction to reduce risk of late effects (1)  Exploit dose-independent opportunity (CQLE) (2)  Sustained protection against cumulative toxicity (3)  Dietary intervention is feasible and popular (4) (1) Pinkawa 2010; Zelefskey 2008; Heemsbergen 2006; Vargas 2005; Jerezak-Fossa, O’Brien 2002; Weiss 1999; Wang 1998; Schulltheis 1997 (2) Heemsbergen 2006; Vargas 2005; Weiss 1999; Wang 1998; Denham 1999 (3) Wedlake, Gulliford 2010 (4) McNair 2011; Oates 2013 The Royal Marsden Diet in other inflammatory conditions Dietary intervention Ulcerative colitis Crohn’s disease Modified (MCT) or low fat (20% kcals) √ (1,2) Elemental formulas √ (3) Pouchitis Prebiotics / Oral fibre supplements √ (5) - √ (5) Probiotics √ (4) - √ (4) Synbiotics √ (4,5) Cochrane reviews: (1) Zachos 2007; (2) Griffiths 1995; (3) Rolfe 2006; Other reviews: (4) Hedin 2007; (5) Wedlake 2013 The Royal Marsden Severe diarrhoea requiring ORS Benefit of selected added nutrients (RS) ORS: Oral Rehydration Solutions RS: Resistant starch Binder 2010; Ann Rev Physiol 72: 297-813 The Royal Marsden The Royal Marsden Rationale for dietary intervention Reduced pancreatic & biliary secretions Ease of absorption Increased SCFA production & benefits Competitive inhibition; immunogenic effects Modified fat (MCT) / low fat (<40g/day) √ √ Elemental formulas √ √ Prebiotics / Oral fibre supplements √ √ Probiotics / synbiotics √ √ Dietary intervention Low lactose / Lactose restriction Reduced risk of lactose intolerance √ The Royal Marsden Total number of RCTs Total reporting positive outcomes Number of Studies 10 n=1260 8 6 4 n=827 n=316 n=224 2 n=64 Elemental formula Low or modified fat Modified fibre Lactose restricted Probiotic Prebiotic synbiotic 10 The Royal Marsden Results: summary table Intervention Key findings of systematic review Weak evidence: 1/4 positive. Largest study abstract only. Noncompliance, differing formulas, feasibility of intubation untested. Elemental formulas Modified (MCT) Limited evidence: 3/4 positive. Multiple interventions, low quality, one positive study abstract only. Compliance not reported. fat or low fat Oral low or high fibre diets Weak evidence: 1/3 positive. Positive study used non-validated outcomes. Multiple interventions. Dietary intake not assessed. Low lactose No evidence: One study high quality. High dropout. Type II error. Probiotics, Prebiotics and synbiotics Probable evidence: 8/9 studies positive including synbiotic (n=1) prebiotic (n=1) and probiotic (n=6). Endpoints (clinical and physiological), strains and strengths (CFU) differ. Concomitant CT not reported. None currently approved for routine use at RMH. Systematic Reviews: Wedlake 2013; McGough 2004 Meta-analysis of probiotic interventions: Hamad (n=10) 2013; Fuccio (n=4) 2019 The Royal Marsden The future for dietary intervention – – – – – Better understanding of mechanisms of damage Identification of site of damage (small or large bowel) Understanding cause of symptoms (e.g. diarrhoea) Nature of response (microbiota-mediated or other) High quality RCTs with informative endpoints Would result in: – Targeted dietary therapy as a simple, cost-effective strategy for radiation-induced GI toxicity The Royal Marsden Acknowledgements Dr HJN Andreyev (Consultant Gastroenterologist in PRD, RMH) Prof K Whelan (King’s College, London) Dr C Shaw (Consultant Dietitian, RMH) T Klopper & L Bottle (Oncology Dietitians, RSCH) Dr H McNair (Research Radiographer, RMH) E Grace, B Benton, A Lalji (PRD Research Team, RMH) Change Presentation title and date in Footer dd.mm.yyyy 13