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The Royal Marsden GI consequences of cancer treatment: Have we forgotten how to care? Jervoise Andreyev Consultant Gastroenterologist in Pelvic Radiation Disease London, UK 1 2 The Royal Marsden Toxicity: an outsider’s view • Wrong questions - bleeding v incontinence • Wrong words - proctitis / “typical?” / “grade 1” • What’s not said - immunology / genetics / internal milieu The Royal Marsden A truth? Oncology loves documenting classifying / staging…… ….Survival or containing …..Not about disease modification Gastroenterology is increasingly about disease modification…. The Royal Marsden Muddling “measuring” with “management”? 5 The Royal Marsden Mr B Cured! • • • • • • 46 year old banker Stage IV low rectal cancer Neoadjuvant chemoradiation Low anterior resection with J pouch 2 years out from treatment 3 different clinicians involved in follow up • • • • • • 2 CT scans But 3 MRI scans 1 colonoscopy 13 follow up appointments CEA checked 7 times No medication does anybody care? 6 The Royal Marsden Mr B • • • • • • Bowels open 10-18 times / day Normal – liquid stool Unable to attend meeting > 20 minutes Bowels open 3 times per night Tenesmus +++ Wears nappies The Royal Marsden Truth no. 2 It is no-one’s job to manage quality of life 8 The Royal Marsden • • • • Sarah 38 year, 10 year old son Cervical cancer 2001 Surgery + radiotherapy 5 different clinicians involved in follow up 2008 • • • • • • • • • Bowels open up to 12 times / day Several times at night Liquid stool, urgency, daily incontinence Intermittent steatorrhoea Nausea +++ Abdominal pain +++ Lost 35% body weight Sub acute obstructive symptoms every 6 weeks Repeatedly told “no treatment” 9 The Royal Marsden A third fundamental truth Curing cancer inevitably risks damage to normal tissues 10 The Royal Marsden Age-standardised one-year relative survival rate, rectal cancer, by sex, England and Wales, 1971-2006 100 Rectal cancer 90 Men Women 80 % survival 70 60 50 40 30 20 10 0 1971-1975 1976-1980 1981-1985 1986-1990 1991-1995 1996-2000* 2001-2003* 2004-2006* Period of diagnosis Symptoms * England only Surgery alone Preoperative radiotherapy Post operative radiotherapy 5-38% 51-72% 49-60% Toilet dependency 6% 30% 53% Excellent function 32% 14% N/A Any incontinence Frykholm 1993, Kollmorgen 1994, Letschert 1994, Lundby 1997, Dahlberg 1998, Miller 1999, Sauer 2004, Peeters 2005, Lundby 2005, Marijnen 2005, Pollack 2006, Pietrzak 2007, Birgisson 2007, Birgisson 2008 11 The Royal Marsden That third fundamental truth Curing cancer inevitably risks damage to normal tissues OK, that’s not quite right….. 12 The Royal Marsden The third fundamental truth Curing cancer inevitably risks damage to normal tissues and so toxicity isn’t wicked…… 13 The Royal Marsden Surviving cancer • UK: 2 million • USA: 13 million • UK: Increasing > 3% per year • USA: Increasing > 11% per year • 25%: Have chronic physical symptoms affecting QOL MacMillan 2008, Hauer-Jensen 2010, NCSI Vision 2011 14 The Royal Marsden The use of pelvic radiotherapy to cure cancer • 40% of all patients with pelvic cancer • 17,000+ per annum in the UK • 300,000 in the Western world The Royal Marsden The use of pelvic radiotherapy to cure cancer • • • • • 9 out of 10 have permanent change in bowel habit 1 in 2 have problems which affect daily activities 1 in 3 people “moderate or severe” 3 out of 20 will eventually need surgery bowel problems often worsen other problems Widmark 1994, Kollmorgen 1994, Crook 1996, Denham 1999, Ooi 2000, al Abany 2002, Henningsohn 2002, Bergmark 2002, Gami 2003, Fokdal 2004, Jephcott 2004, Olopade 2005, Abayomi 2009, Barker 2009, Capp 2009 The Royal Marsden UK hospitals with ≥1 gastroenterologists with a specialist interest in IBD 8,500 moderate or severe Gl dysfunction after pelvic radiotherapy / year 7,000 GI cancers with toilet dependency / year 12,000 IBD/ year The Royal Marsden Clinic Attendances at the RMH late effects GI clinic 100 Numbers of patients per month 90 80 70 60 50 40 30 20 10 0 The Royal Marsden Oncological Symptom assessment & control The Royal Marsden 20 The Royal Marsden Symptom assessment & control What do symptoms mean? - very little! 21 The Royal Marsden Mr. H • 76 year old, normal bowel function pre-RT • Prostate cancer, 1 year after conformal RT • Normal PSA • Bowels open x4 per day • Urgency • Often loose stool • Faecal incontinence weekly • Tenesmus • Perianal soreness Too much fibre Mr. J • 64 year old, normal bowel function pre-RT • Prostate cancer, 1 year after IMRT • Bowels open 3-6 per day • Urgency • Often loose stool • x2 faecal incontinence / month • Tenesmus • Perianal soreness Giardia & 2cm sigmoid polyp 22 The Royal Marsden Why do patients develop GI symptoms? 23 The Royal Marsden The physiological model Inflammatory changes Any insult Oedema ischaemia Cell death Atrophy / loss of stem cells fibrosis Potentially alter specific GI physiological function(s) Unrelated factors • • • • medication side effects stress sepsis premorbid conditions Symptoms 24 The Royal Marsden Radiotherapy is not about anatomy 25 The Royal Marsden Chronic loose stool / Diarrhoea 1:2 Ludgate 1985 26 Arlow 1987 11 Danielsson 1991 20 Ford 1992 12 % % % % % bile acid malabsorption 50 73 65 83 1 large bowel strictures 15 9 - - 3 bacterial overgrowth 8 - 45 - 12 diverticular disease 8 9 - - 22 relapse 4 - - - 10 (lactose intolerance - - - - 5) pelvic sepsis 4 - - - 3 new GI neoplasia - - - - 8 drug related - - - - 5 IBD - - - - 4 proctopathy - - - - 33 other - - - - 5 n= Andreyev 2005 78 26 The Royal Marsden GI symptoms: the Royal Marsden GI Unit algorithmic approach 27 The Royal Marsden RMH algorithm version 7 Bleeding Nausea Bloating Nocturnal need to defecate Borborygmi Pain - abdomen Change in bowel habit Pain - back (new onset) Constipation Pain – perineal / anal / rectal Flatulence (oral / rectal) Tenesmus Frequency of defaecation Urgency Incontinence / soiling / leakage Vomiting Loss of rectal sensation Weight loss Men Diarrhoea median 6 symptoms (range 1-16) / loose stool Perianal pruritus Evacuationmedian difficulty Steatorrhoea (range 4-16) Women 11 symptoms Mucus excess Benton 2011 The Royal Marsden Which symptom is the worst? 40% 30% Male Female 20% 10% 0% Gillespie AP&T 2007 29 The Royal Marsden RMH algorithm version 7 For each of the 23 symptoms: • defined list of tests • defined sequence of treatments The Royal Marsden Using the concept of physiological algorithmic approach Management of symptoms becomes straightforward Identify each symptom accurately Arrange appropriate tests to identify which physiological deficits are present ->obvious treatment options 31 The Royal Marsden Mr B • • • • • • Bowels open 10-18 times / day Normal – liquid stool Unable to attend meeting > 20 minutes Bowels open 3 times per night Tenesmus +++ Wears nappies 33 The Royal Marsden Mr B • • some inflammation in his pouch no other abnormalities Treatment given • Normacol • Toileting exercises • Glycerine suppositaries After 6 weeks • Bowels open 4 times a day • No urgency incontinence • No nocturnal defaecation 34 The Royal Marsden • • • • Sarah 38 year, 10 year old son Cervical cancer 2001 Surgery + radiotherapy 5 different clinicians involved in follow up 2008 • • • • • • • • • Bowels open up to 12 times / day Several times at night Liquid stool, urgency, daily incontinence Intermittent steatorrhoea Nausea +++ Abdominal pain +++ Lost 35% body weight Sub acute obstructive symptoms every 6 weeks Repeatedly told “no treatment” The Royal Marsden Sarah 1. Bile acid malabsorption (SeHCAT scan 0%) Rx: Colesevelam 2. Small bowel bacterial overgrowth (D2 aspirate) Rx: Ciprofloxacin 3. Free fatty acid malabsorption Rx: 40-50g fat diet 4. Gastric bile reflux Rx: Sucralfate suspension • • • • • • Within 4 days formed stool 2 /day No more urgency or faecal incontinence No further obstructive episodes Nausea settled Within 3 weeks completely normal “it’s a miracle” 37 The Royal Marsden A third fundamental truth Curing cancer inevitably risks damage to normal tissues and so toxicity isn’t wicked…… 38 The Royal Marsden A third fundamental truth Curing cancer inevitably risks damage to normal tissues and so toxicity isn’t wicked…… but what is wicked…… ….is doing nothing about it. 39 The Royal Marsden Conclusions 1. Loads of patients 2. In loads of trouble 3. Need referral pathways for expert care Because • Symptoms are due to correctable physiological dysfunction not “anatomical syndromes” • Physiological deficits are easily diagnosed by appropriate tests • Targeted treatment works • Disease modification therapies are the future