Liam MurrayCancer Epidemiology and Prevention Research Group

Queen’s University Belfast

Dublin September 3rd 2009

The Northern Ireland Barrett’s Register: incidence and risk factors for progression to

cancer

What is Barrett’s oesophagus?

Shaheen NJ, Richter JE. Lancet 2009;373:850-861

Why is Barrett’s oesophagus important?

OAC trends by sex and deprivation category, England and Wales, 1986–2001

The American Journal of Gastroenterology (2008) 103, 2694–2699

Trends in Barrett’s oesophagus - USA

Conio et al Gut 2001;48:304-309

Copyright ©2009 BMJ Publishing Group Ltd.

Corley, D A et al. Gut 2009;58:182-188

Recent trends in Barrett's oesophagus diagnosis in the USA

Copyright ©2009 BMJ Publishing Group Ltd.

Corley, D A et al. Gut 2009;58:182-188

Recent trends in Barrett's oesophagus prevalence in the USA

Cancer risk in Barrett's oesophagus by study size

Rationale for the Northern Ireland Barrett’s Register

• Substantial increase in rate of diagnosis of BO

• Very large increases in prevalence of diagnosed BO

• Lack of clarity on cancer risk

• effectiveness/cost-effectiveness of endoscopic surveillance?

• Groups at high risk of progression are not well established

• Biomarkers for progression have not been identified

• Very limited investigation of the factors associated with progression to cancer

• any modifiable lifestyle factors?

• How should BO patients be managed?

• What advice can Barrett’s patients be given?

The Northern Ireland Barrett’s Register(1993-2005)

All oesophageal biopsy specimens

from NI hospitals1993-2005

Biopsy at OGJColumnar Epithelium

of oesophagus

No Columnar

Epithelium

SIM

present Unclassified

DeathsIncident cancers

& HGD

Not present

Manual review

of path reports

Individual patients identified

Note review / Pathology review

Linkage to Cancer Registry / Death files

Malignancy

Prevalence of BO diagnosis in Northern Ireland

0

100

200

300

400

500

600

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

All BO

SIM

The Northern Ireland Barrett’s Register:follow-up data

Incidence of OAC in Barrett’s oesophagus

Patient Characteristics Number of patients (pyr), total events

Incidence of events (per 1,000 pyr)

oesophageal cancer

oesophageal and gastric cardia cancer

oesophageal cancer and HGD

oesophageal/ gastric cardia cancer and HGD

All patients 7585 (38076), 90 1.5 (1.1-1.9) 1.8 (1.4-2.3) 2.0 (1.6-2.5) 2.4 (1.9-2.9)

SIM at index biopsy

Present 3533 (18901), 73 2.34 (1.7-3.2) 2.9 (2.2-3.8) 3.3 (2.6-4.3) 3.9 (3.0-4.9)

Absent 2865 (15072), 12 0.4 (0.2-1.00) 0.7 (0.3-1.2) 0.6 (0.3-1.10 0.8 (0.4-1.4)

Unknown 1187 (4103), 5 1.0 (0.2-2.5) 1.2 (0.4-2.8) 1.0 (0.2-2.5) 1.2 (0.4-2.8)

Age at diagnosis

<50 2071 (10675), 12 0.5 (0.2-1.1) 0.7 (0.3-1.4) 0.9 (0.4-1.7) 1.1 (0.5-2.0)

50-59 1689 (8610), 19 1.0 (0.5-2.0) 1.5 (0.8-2.6) 1.7 (1.0-2.9) 2.2 (1.4-3.4)

60-69 1724 (8897), 34 2.4 (1.5-3.6) 3.1 (2.1-4.5) 3.0 (2.0-4.4) 3.8 (2.6-5.3)

70-79 1422 (7171), 16 1.8 (1.0-3.1) 2.0 (1.1-3.3) 2.1 (1.2-3.4) 2.2 (1.3-3.6)

80+ 679 (2733), 7 2.2 (0.8-4.8) 2.2 (0.8-4.8) 2.6 (1.0-5.3) 2.6 (1.0-5.3)

?Subgroups at high risk of progression from BO to OAC: Gender

Incidence of events per 1,000 pyr

Number of patients (pyr), total events

oesophageal cancer

oesophageal and gastric

cardia cancer

oesophageal cancer and

HGD

oesophageal/ gastric cardia

cancer and HGD

Male4413 (21949),

68 2.0 (1.5-2.7) 2.4 (1.8-3.2) 2.7 (2.0-3.50 3.1 (2.4-3.9)

Female3172 (16127),

220.7 (0.4-1.3) 1.1 (0.6-1.7) 1.1 (0.6-1.7) 1.4 (0.9-2.1)

Patients with endoscopically visible segment and SIM on histology

Male1582 (8423),

382.6 (1.6-4.0) 3.0 (1.9-4.4) 4.2 (2.9-5.8) 4.5 (3.2-6.2)

Female906 (4844),

172.1 (1.0-3.8) 2.9 (1.6-4.8) 2.7 (1.4-4.6) 3.5 (2.0-5.6)

The Northern Ireland Barrett’s Register

?Subgroups at high risk of progression from BO to OAC: Length of segment and dysplasia

Patient CharacteristicsNumber of patients (pyr),

total events

Incidence of events per 1,000 pyr

oesophageal cancer

oesophageal and gastric

cardia cancer

oesophageal cancer and HGD

oesophageal/ gastric cardia

cancer and HGD

All patients 2488 (13267), 55 2.4 (1.6-3.4) 2.9 (2.1-4.0) 3.6 (2.7-4.8) 4.1 (3.1-5.4)

Length of BO

Long 960 (5759), 30 3.1 (1.9-4.9) 3.8 (2.4-5.8) 4.5 (2.9-6.6) 5.2 (3.5-7.4)

Short 289 (1286), 3 0 (0-2.8) 0 (0-2.8) 2.3 (0.5-6.8) 2.3 (0.5-6.8)

Length unknown

1239 (6222), 222.2 (1.2-3.8) 2.7 (1.6-4.4) 3.1 (1.8-4.8) 3.5 (2.2-5.3)

DysplasiaNo

2136 (11253), 35 1.8 (1.1-2.9) 2.2 (1.4-3.2) 2.8 (1.9-3.9) 3.1 (2.1-4.3)

Low grade

182 (1032),13 8.8 (4.0-16.7) 9.8 (4.7-18.0) 11.7 (6.1-20.5)12.7 (6.7-21.7)

Unknown

170 (990), 5 2.0 (0.2-7.2) 4.0 (1.1-10.3) 3.0 (0.6-8.8) 5.0 (1.6-11.8)

Patients with endoscopically visible segment and SIM on histology

The Northern Ireland Barrett’s Register

Clinical factors associated with progression to OAC: interim results of the case note review

Factor Well-defined BO group

HR (95% CI) P value

Reflux symptoms at referral

No Unknown Yes

257 (23.5) 153 (13.9) 685 (62.6)

1 0.6 (0.2-1.8) 0.5 (0.2-1.0)

0.36 0.04

Markers of oesophageal inflammation

No/unknown Yes

563 (51.4) 532 (48.6)

1 2.4 (1.2-4.6) 0.01

PPIs No Yes

150 (13.7) 945 (86.3)

1 3.6 (1.1—11.6) 0.03

H2 antagonists No Yes

833 (76.1) 262 (23.9)

1 2.3 (1.1-4.5) 0.02

Aspirin No Yes

973 (88.9) 122 (11.1)

1 1.8 (0.7-4.8) 0.24

NSAIDs No Yes

1034 (94.4) 61 (5.6)

1 0.8 (0.2-3.3) 0.72

H. pylori eradication therapy

No Yes

887 (81.0) 208 (19.0)

1 0.8 (0.3-1.9) 0.56

Lifestyle factors associated with progression to OAC

Factor Well-defined BO group

HR (95% CI) P value

BMI <2525-<3030 or moreUnknown

78 (7.1)123 (11.2)

69 (6.3)825 (75.3)

11.0 (0.3-3.0)0.7 (0.2-3.3)0.6 (0.2-1.6)

0.930.700.30

Weight 1st quartile2nd quartile3rd quartile4th quartileUnknown

168 (15.3)180 (16.4)177 (16.2)185 (16.9)385 (35.2)

11.1 (0.3-4.7)1.8 (0.5-6.3)1.4 (0.4-5.2)2.6 (0.8-8.0)

0.880.380.580.10

Smoking NeverEx-smokerCurrentUnknown

471 (43.0)232 (21.2)256 (23.4)136 (12.4)

10.8 (0.4-1.9)0.6 (0.3-1.5)0.3 (0.1-1.1)

0.640.310.07

Alcohol None<10 units/wk10-20 units/wk>20 units/wkUnknown

337 (30.8)317 (28.9)149 (13.6)

71 (6.5)221 (20.2)

11.9 (0.8-4.8)1.0 (0.2-4.1)

4.3 (1.3-14.0)3.7 (1.4-10.0)

0.170.990.020.01

Conclusions

• Confirm a low risk of progression to cancer/HGD

• Groups at higher risk

• long segment BO

• dysplasia at baseline

• age 60-69 at baseline

• Rate of progression similar in men and women

• Oesophageal inflammation at diagnosis associated with increased risk of

progression?

• No lifestyle risk factors for progression identified

• Inadequate data from case note review

• Prospective cohorts of BO required

Northern Ireland Barrett’s Register: Investigators and funders

• Prof Liam Murray, CEPRG/NICR, QUB• Dr Brian Johnston, Belfast HSCT• Dr Anna Gavin, NICR, QUB• Dr Damian McManus, Belfast HSCT• Dr Helen Mulholland, CEPRG• Dr Lesley Anderson, CEPRG• Dr Shivaram Bhat, CEPRG

Collaborators• Dr Laura Hardie, Leeds University• Dr Rebecca Fitzgerald, University of Cambridge• Dr Lawrence Lovat, UCLH • Prof Marco Novelli, UCLH

Clerical staff• Kate Donnelly (Data abstractor)• Rosemary Ward (Data abstractor)

Ulster Cancer Foundation