Adenocarcinoma of the Esophagus and Gastroesophageal Junction

1
Adenocarcinoma of the Esophagus and
Gastroesophageal Junction

• Steven R. Alberts, MD MPH
• Medical Oncology
• Mayo Clinic
• Rochester, MN

2
Adenocarcinoma of the Esophagus - An Evolving
Story

• Progressive decline in stomach cancer since early
  1900s
• Refrigeration of food
• Decrease in smoked and salted foods

3
Mortality from Stomach and Esophageal Cancer
4
Esophageal and GE Junction Cancers

• Recent dramatic increase in adenocarcinomas of
  the esophagus and gastroesophageal junction
• More rapid increase than melanomas

5
Esophagus and GE Junction
6
Occurrence of Esophageal and Gastric Cancer

• New Cases in 2004
• Esophagus 14,250
• Men 10,860
• Women 3,390
• Stomach 22,710
• Men 13,640
• Women 9,070
• One-third of stomach cancers from GE Junction and
  Cardia
• Jemal A, et al. CA Cancer J Clin 548-29, 2004

7
Pathology - American College of Surgeons National
Cancer Database

• 1973-82 1994
• (N5644) (N5044)
• Adenocarcinoma 13 42
• Squamous Cell 79 52
• Yang PC, et al. Cancer 61612-17, 1988
• Daly JM, et al. J Am Coll Surg 190562-73, 2000

8
Incidence Trends SEER, 1974-78 to Gastric
Adenocarcinoma 1994-98
Male
Female
5
5
Noncardia Black
Noncardia White
Cardia White
Cardia Black
Rate per 100,000 person-years
0.5
0.5
0.05
0.05
Year of diagnosis
Year of diagnosis
9
Esophageal Cancer Incidence Trends SEER, 1974-78
to 1994-98
Male
Female
gt350-fold increase in esophageal adenocarcinoma
5
5
Squamous Cell Carcinoma - Black
Squamous Cell Carcinoma - White
Adenocarcinoma - White
Rate per 100,000 person-years
Adenocarcinoma - Black
0.5
0.5
0.05
0.05
Brown Devesa, 2002
Year of diagnosis
Year of diagnosis
10
Esophageal AdenocarcinomaIncidence Trends,
Males, Europe
Botterweck AAM, et al, 2000
11
Age-Specific Incidence Rates White Males,
SEER, 1995-1999
12
Age-Specific Incidence Rates White Females,
SEER, 1995-1999
13
Male to Female Incidence Rate Ratios
SEER, 1995-1999
14
Esophageal AdenocarcinomaOne-year Survival
Rates, SEER
Eloubeidi MA, et al, Am J Gastroenterol 2003
15
5-year survival for patients with esophageal
cancer

• Stage I 79
• Stage IIA 38
• Stage IIB 27
• Stage III 14
• Stage IV 5

16
Esophageal Adenocarcinoma Survival Rates,
SEER
34 to 44
5 to 13
Eloubeidi MA, et al., Am J Gastroenterol 2003
17
Esophageal Adenocarcinoma Stage at
Diagnosis, SEER
Eloubeidi MA, et al., Am J Gastroenterol 2003.
18
Environmental Risk Factors

• Esophageal Adenocarcinoma

19
(No Transcript)
20
Cigarette Smoking U.S. Multicenter study

• Smoking Status OR 95 CI
• Never smoker 1.0
• Current smoker 2.2 (1.4-3.3)
• Ex-smoker 2.0 (1.4-2.9)
• Pack-years of Smoking
• lt14 1.4 (0.8-2.2)
• 14-31 1.6 (1.0-2.6)
• 32-54 2.9 (1.8-4.5)
• gt54 2.8 (1.8-4.4)

Gammon MD, et al. JNCI, 1997.
21
Smoking Cessation

• Years Stopped OR (95 CI)
• lt11 2.7 (1.6-4.4)
• 11-20 2.3 (1.4-3.8)
• 21-30 1.9 (1.1-3.2)
• gt30 1.2 (0.7-2.2)

22
(No Transcript)
23
U.S. Current Cigarette Smokers 1965 to 1998
Brown LM, Devesa SS. Surg Oncol Clin N Am, 2002.
24
(No Transcript)
25
Usual Adult Body Mass Index U.S.
Multicenter Study

• BMI Quartiles OR 95 CI
• I Low 1.0
• II 1.3 (0.8-2.2)
• III 2.0 (1.3-3.3)
• IV High 2.9 (1.8-4.7)

Chow WH, et al. JNCI, 1998.
26
(No Transcript)
27
U.S. Obese adults 1960-62 to 1988-94
Brown LM, Devesa SS. Surg Oncol Clin N Am, 2002.
28
(No Transcript)
29
Waist-to-Hip Ratio and Intermediate
Markers in Barretts Esophagus

• Percent with Intermediate Markers
• Waist-to-hip ratio 4N Aneuploidy 9pLOH
  17pLOH
• Quartile I 5 5 49
  18 II 8 7 48 15
• III 11 12 58 18
• Quartile IV 14 17 67 29

• Association with abdominal obesity consistent
  with
• increased risk in males

Vaughan TL, et al. Cancer Epidemiol Biomarkers
Prev 2002.
30
(No Transcript)
31
Gastroesophageal RefluxSouthern California
Kaiser Study

• Reflux OR 95 CI
• No 1.0
• Yes 2.1 (1.2-3.6)
• Duration (Years)
• 1-5 1.2 (0.5-3.0)
• gt5 2.7 (1.5-4.9)

Chow WH, et al. JAMA, 1995.
32
Use of Medications Southern California
Kaiser Study

• Medications OR 95 CI
• No 1.0
• Anticholinergics only 0.8 (0.4-1.5)
• H2 antagonists only 0.7 (0.3-1.6)
• Both 0.5 (0.1-1.4)

33
Gastroesophageal Reflux U.S.
Multi-Center Study

• Reflux symptoms
• (times/year) OR 95 CI
• Never 1.0
• 1-2 0.5 (0.2-1.0)
• 3-12 1.2 (0.6-2.2)
• 13-104 2.0 (1.2-3.2)
• 105-364 3.4 (1.9-6.1)
• gt364 5.5 (3.2-9.3)

Farrow DC, et al. Cancer Causes Control, 2000.
34
BMI, Reflux Symptoms, and Risk of Esophageal
Adenocarcinoma

• Reflux Symptoms
• BMI Quartile No Yes
• I 1.0 1.0
• II 2.0 2.0
• III 4.4 3.3
• IV 7.6 8.8
• plt0.05

Lagergren J, et al. Ann Intern Med 1999.
35
Reflux Disease Incidence Rates Among U.S. Male
Veterans
Brown LM, Devesa SS. Surg Oncol Clin N Am, 2002.
36
Progression of Esophageal Adenocarcinoma

• Gastroesophageal Reflux Disease
• Metaplasia/Barretts Esophagus
• Low Grade Dysplasia
• High Grade Dysplasia
• Adenocarcinoma

37
Diet
38
Potential Dietary Risk Factors

• Factor Risk
• Fruits vegetables
• Dietary fiber
• Antioxidants
• Total fat
• Reflux-inducing foods --
• Heterocyclic amines --

39
Population Attributable Risks U.S.
Multicenter Study

• Risk Factor PAR (95 CI)
• Smoking ever 40 (26-56)
• BMI upper 3 quartiles 41 (24-61)
• Reflux symptoms 30 (20-42)
• Fruits vegetables 15 (6 -35)
• (lt2 times/day)
• All factors combined 79 (67-87)

Engel LS, et al. JNCI 2003.
40
Helicobacter pylori
41
Helicobacter pylori and cagA Status
U.S. Multicenter Study

• H. pylori status OR 95 CI
• Negative 1.0
• Positive 0.7 0.4-1.1
• cagA status
• Negative 1.0 0.5-1.7
• Positive 0.4 0.2-0.8

Chow WH, et al. Cancer Res, 1998.
42
Blaser MJ. J Infect Dis, vol 179, pp 1523-30.
43
NSAIDs
44
Use of Nonseroidal Anti-Inflammatory
Drugs (NSAID)

• Barretts Esophagus
• NSAID Aneu-
• Use EA 4N ploidy 9pLOH 17pLOH
• Never 1.0 1.0 1.0 1.0 1.0
• Former 0.4 1.1 0.2 0.9 0.7
• Current 0.4 0.6 0.6 1.1 0.3

Farrow DC, et al. Cancer Epidemiol Biomark Prev
1998. Vaughan TL, et al. Cancer Epidemiol
Biomark Prev 2002.
45
SummaryEnvironmental Risk Factors

• Population Cancer
• Risk Factor Trend Trend
• Reflux disease
• Overweight
• Smoking
• H. Pylori
• Fruits/vegetables
• NSAID Use

46
Summary

• Potential opportunity for prevention and early
  intervention
• Managing obesity
• Smoking cessation
• Monitoring patients with reflux
• Improving diet
• Use of risk modifying agents in high-risk
  populations

47
(No Transcript)