The Royal Marsden

1

GI consequences of cancer treatment:

Have we forgotten how to care?

Jervoise AndreyevConsultant Gastroenterologist in Pelvic Radiation DiseaseLondon, UK

The Royal Marsden2

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

Oncology loves documenting classifying / staging……….Survival or containing

…..Not about disease modification

A truth?

Gastroenterology is increasingly about disease

modification….

The Royal Marsden

Muddling “measuring” with “management”?

The Royal Marsden5

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

Cured!

But does anybody care?

The Royal Marsden6

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

It is no-one’s job tomanage quality of life

Truth no. 2

The Royal Marsden8

• 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”

Sarah

The Royal Marsden9

A third fundamental truth

Curing cancer inevitably risks damage to normal

tissues

The Royal Marsden10

Rectal cancer

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

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

1971-1975 1976-1980 1981-1985 1986-1990 1991-1995 1996-2000*

2001-2003*

2004-2006*

0

10

20

30

40

50

60

70

80

90

100

Men Women

Period of diagnosis

% survival

Figure 3.1: Age standardised relative survival (%) at one, five, ten and twenty years since diagnosis, female breast cancer, England and Wales, 1971-2003

* England only

Age-standardised one-year relative survival rate, rectal cancer, by sex, England and Wales, 1971-2006

The Royal Marsden11

That third fundamental truth

Curing cancer inevitably risks damage to normal

tissuesOK, that’s not quite right…..

The Royal Marsden12

The third fundamental truth

Curing cancer inevitably risks damage to normal

tissuesand so toxicity isn’t wicked……

The Royal Marsden13

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

The Royal Marsden14

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

• 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 use of pelvic radiotherapy to cure cancer

The Royal Marsden

8,500 moderate or severe Gl dysfunction after pelvic radiotherapy / year

12,000 IBD/ year

7,000 GI cancers with toilet dependency / year

UK hospitals with ≥1gastroenterologists with a specialistinterest in IBD

The Royal Marsden

0

10

20

30

40

50

60

70

80

90

100

Clinic Attendances at the RMH late effects GI clinic

July 2008

Jan 2010July 2010Jan 2011July2011

Jan 2008

Jan 2009July 2009

July 2007

Jan 2007

Nu

mb

ers

of

pati

en

ts p

er

mon

th

The Royal Marsden

Oncological

Symptom assessment & control

The Royal Marsden

The Royal Marsden20

What do symptoms mean?

- very little!

Symptom assessment & control

The Royal Marsden21

• 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

Mr. H

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

The Royal Marsden22

Why do patients develop GI symptoms?

The Royal Marsden23

The physiological model

Any insult

Symptoms

ischaemia

fibrosis

Unrelated factors• medication side effects

• stress• sepsis• premorbid conditions

Potentially alter specific GI physiological function(s)

Cell death

Atrophy / loss of

stem cells

Oedema

Inflammatory changes

The Royal Marsden24

Radiotherapy is not about anatomy

The Royal Marsden25

Chronic loose stool / Diarrhoea 1:2

% % % % %

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

Ludgate Arlow Danielsson Ford Andreyev 1985 1987 1991 1992 2005

n= 26 11 20 12 78

The Royal Marsden26

GI symptoms: the Royal Marsden GI Unit

algorithmic approach

The Royal Marsden27

RMH algorithm version 7Bleeding 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)

The Royal Marsden

Gillespie AP&T 2007

Leak

age

PR b

leed

ing

Win

d

Bloat

ing

Slee

p di

stur

banc

e

Diarrho

ea

Cons

tipat

ion

Pain

Muc

us

Urgen

cy

Other

0%

10%

20%

30%

40%

Which symptom is the worst?

Male

Female

The Royal Marsden29

For each of the 23 symptoms:

• defined list of tests • defined sequence of treatments

RMH algorithm version 7

The Royal Marsden

Identify each symptom accurately

Management of symptoms becomes straightforward

Using the concept of physiological algorithmic approach

Arrange appropriate tests to identify which physiological

deficits are present->obvious treatment

options

The Royal Marsden31

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 Marsden33

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

The Royal Marsden34

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”

Sarah• 38 year, 10 year old son• Cervical cancer 2001• Surgery + radiotherapy• 5 different clinicians involved in follow up

The Royal Marsden

Sarah1. 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 refluxRx: 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”

The Royal Marsden37

A third fundamental truth

Curing cancer inevitably risks damage to normal

tissuesand so toxicity isn’t wicked……

OK,

that’

s stil

l not

quite

right…

..

The Royal Marsden38

A third fundamental truth

Curing cancer inevitably risks damage to normal

tissuesand so toxicity isn’t wicked……

….is doing nothing about it.but what is wicked……

The Royal Marsden39

Conclusions

1. Loads of patients2. In loads of trouble3. 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