1. GI consequences of cancer treatment: Have we forgotten how to care?
Jervoise Andreyev Consultant Gastroenterologist in Pelvic Radiation Disease
London, UK

2. Toxicity: an outsider’s view
Wrong questions
- bleeding v incontinence
Wrong words
- proctitis / “typical?” / “grade 1”
What’s not said
immunology / genetics / internal milieu

3. A truth? Oncology loves documenting classifying / staging……
….Survival or containing
…..Not about disease modification
Gastroenterology is increasingly about disease modification….

4. Muddling “measuring”
with “management”?

5. Cured! But does anybody care? Mr B 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
3 MRI scans
1 colonoscopy
13 follow up appointments
CEA checked 7 times
No medication
But does anybody care?

6. 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

7. It is no-one’s job to
manage quality of life
Truth no. 2

8. Sarah Cervical cancer 2001 Surgery + radiotherapy
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. A third fundamental truth
Curing cancer inevitably risks damage to normal tissues

10. Preoperative radiotherapy Post operative radiotherapy
Rectal cancer
Symptoms
Surgery alone
Preoperative radiotherapy
Post operative radiotherapy
Any incontinence
5-38%
51-72%
49-60%
Toilet dependency 6%
30%
53%
Excellent function
32%
14%
N/A
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. That third fundamental truth OK, that’s not quite right…..
Curing cancer inevitably risks damage to normal tissues
OK, that’s not quite right…..

12. The third fundamental truth
Curing cancer inevitably risks damage to normal tissues
and so
toxicity isn’t wicked……

13. Surviving cancer UK: 2 million USA: 13 million
MacMillan 2008, Hauer-Jensen 2010, NCSI Vision 2011
UK: Increasing > 3% per year
USA: Increasing > 11% per year
25%: Have chronic physical
symptoms affecting QOL

14. 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

15. 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

16. 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

17. Jan 2007 July 2007 Jan 2008 July 2008 Jan 2009 July 2009 Jan 2010
Numbers of patients per month
Jan 2007
July 2007
Jan 2008
July 2008
Jan 2009
July 2009
Jan 2010
July 2010
Jan 2011
July2011

18. Symptom assessment & control
Oncological
Symptom assessment & control

20. Symptom assessment & control
What do symptoms mean?
- very little!

21. Too much fibre Mr. H Mr. J 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
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
Mr. J
Giardia
&
2cm sigmoid polyp

22. Why do patients develop GI symptoms?

23. The physiological model
Cell death
Atrophy / loss of stem cells
Oedema
Inflammatory changes
The physiological model
Any insult
ischaemia
Potentially alter specific
GI physiological function(s)
fibrosis
Symptoms
Unrelated factors
medication side effects
stress
sepsis
premorbid conditions

24. Radiotherapy is not about anatomy

25. Chronic loose stool / Diarrhoea 1:2
Ludgate Arlow Danielsson Ford Andreyev n= %
bile acid malabsorption 50 73 65 83 1
large bowel strictures 15 9 - 3
bacterial overgrowth 8 45 12
diverticular disease 22
relapse 4 10
(lactose intolerance 5)
pelvic sepsis
new GI neoplasia
drug related 5
IBD
proctopathy 33
other

26. the Royal Marsden GI Unit algorithmic approach
GI symptoms:
the Royal Marsden GI Unit
algorithmic approach

27. RMH algorithm version 7 Men median 6 symptoms (range 1-16)
Bleeding
Nausea
Bloating
Nocturnal need to defecate
Borborygmi
Pain - abdomen
Change in bowel habit
Pain - back (new onset)
Constipation
Pain – perineal / anal / rectal
Diarrhoea / loose stool
Perianal pruritus
Evacuation difficulty
Steatorrhoea
Flatulence (oral / rectal)
Tenesmus
Frequency of defaecation
Urgency
Incontinence / soiling / leakage
Vomiting
Loss of rectal sensation
Weight loss
Mucus excess
Benton 2011
Men median 6 symptoms (range 1-16)
Women median 11 symptoms (range 4-16)

28. Gillespie AP&T 2007

29. RMH algorithm version 7 For each of the 23 symptoms:
defined list of tests
defined sequence of treatments

30. ->obvious treatment options
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. 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. 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. Sarah Cervical cancer 2001 Surgery + radiotherapy
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”

36. 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: g 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. A third fundamental truth OK, that’s still not quite right…..
Curing cancer inevitably risks damage to normal tissues
OK, that’s still not quite right…..
and so
toxicity isn’t wicked……

38. A third fundamental truth
Curing cancer inevitably risks damage to normal tissues
and so
toxicity isn’t wicked……
….is doing nothing about it.
but what is wicked……

39. Conclusions Loads of patients In loads of trouble
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