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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
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Toxicity: an outsider’s view
• Wrong questions
- bleeding v incontinence
• Wrong words
- proctitis / “typical?” / “grade 1”
• What’s not said
- immunology / genetics / internal milieu
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A truth?
Oncology loves documenting
classifying / staging……
….Survival or containing
…..Not about disease modification
Gastroenterology is increasingly
about disease modification….
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Muddling “measuring”
with “management”?
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Mr B
Cured!
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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
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2 CT scans
But
3 MRI scans
1 colonoscopy
13 follow up appointments
CEA checked 7 times
No medication
does anybody care?
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Mr B
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Bowels open 10-18 times / day
Normal – liquid stool
Unable to attend meeting > 20 minutes
Bowels open 3 times per night
Tenesmus +++
Wears nappies
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Truth no. 2
It is no-one’s job to
manage quality of life
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Sarah
38 year, 10 year old son
Cervical cancer 2001
Surgery + radiotherapy
5 different clinicians involved in follow up
2008
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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”
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A third fundamental truth
Curing cancer inevitably risks
damage to normal tissues
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Age-standardised one-year relative survival rate, rectal cancer,
by sex, England and Wales, 1971-2006
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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
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That third fundamental truth
Curing cancer inevitably risks
damage to normal tissues
OK, that’s not quite right…..
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The third fundamental truth
Curing cancer inevitably risks
damage to normal tissues
and so
toxicity isn’t wicked……
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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
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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
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The use of pelvic radiotherapy to cure cancer
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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
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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
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Oncological
Symptom
assessment
& control
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Symptom
assessment
& control
What do symptoms mean?
- very little!
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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
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Why do patients develop GI
symptoms?
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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
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medication side effects
stress
sepsis
premorbid conditions
Symptoms
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Radiotherapy is not about anatomy
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Chronic loose stool / Diarrhoea 1:2
Ludgate
1985
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Arlow
1987
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Danielsson
1991
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Ford
1992
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%
%
%
%
%
bile acid malabsorption
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73
65
83
1
large bowel strictures
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3
bacterial overgrowth
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45
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diverticular disease
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9
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relapse
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(lactose intolerance
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5)
pelvic sepsis
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new GI neoplasia
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drug related
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IBD
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proctopathy
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other
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5
n=
Andreyev
2005
78
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GI symptoms:
the Royal Marsden GI Unit
algorithmic approach
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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
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Which symptom is the worst?
40%
30%
Male
Female
20%
10%
0%
Gillespie AP&T 2007
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RMH algorithm version 7
For each of the 23 symptoms:
• defined list of tests
• defined sequence of treatments
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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
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Mr B
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Bowels open 10-18 times / day
Normal – liquid stool
Unable to attend meeting > 20 minutes
Bowels open 3 times per night
Tenesmus +++
Wears nappies
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Mr B
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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
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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”
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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
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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”
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The Royal Marsden
A third fundamental truth
Curing cancer inevitably risks
damage to normal tissues
and so
toxicity isn’t wicked……
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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.
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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