Transcript 2007_files/Meyerhardt CALGB 89803 diet ASCO2007

The impact of dietary patterns on cancer
recurrence and survival in patients with stage III
colon cancer: findings from CALGB 89803
Jeffrey A. Meyerhardt1, Donna Niedzwiecki2, Donna Hollis2,
Leonard B. Saltz3, Walter Willett4, Robert J. Mayer1, Charles
S. Fuchs1
1Dana-Farber
Cancer Institute, Boston, MA; 2CALGB
Statistical Center, Durham, NC; 3Memorial Sloan-Kettering
Cancer Center, New York, NY; 4 Harvard School of Public
Health, Boston, MA
Revised Abstract
Context: Dietary factors have been associated with the risk of developing colon cancer, however, the influence
of diet on patients with established disease is unknown.
Objective: Determine influence of dietary patterns on cancer recurrences & mortality of colon cancer survivors.
Design, Setting, Patients: We conducted a prospective observational study of 1,009 patients with stage III
colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on dietary intake using
a semi-quantitative food frequency questionnaire during and 6 months after adjuvant chemotherapy. We
identified two major dietary patterns, prudent and Western, by factor analysis. The prudent pattern was
characterized by high fruit and vegetable, poultry and fish intakes; the Western pattern was characterized by
high meat, fat, refined grains and dessert intakes. Patients were followed for cancer recurrence or death.
Results: A higher intake of a Western pattern diet after cancer diagnosis was associated with a significantly
increased risk of colon cancer recurrence or death (disease-free survival). Compared with patients in the
lowest quintile of Western pattern diet, those in the highest quintile experienced an adjusted hazard ratio for
recurrence or death of 3.91 (95% confidence interval [CI], 2.21 – 6.89; P for trend<0.0001), Western pattern
diet was associated with a similar detriment in recurrence-free survival (adjusted P for trend<0.0001) and
overall survival (adjusted P for trend<0.0001). The reduction in disease-free survival with a Western pattern
diet was not significantly modified by gender, age, nodal stage, body mass index, physical activity level,
baseline performance status, or treatment arm. In contrast, the prudent pattern diet was not significantly
related to cancer recurrence or mortality.
Conclusion: Higher intake of a Western pattern diet may increase the risk of recurrence and mortality among
patients with stage III colon cancer patients treated with surgery and adjuvant chemotherapy. Further studies
are needed to delineate which components of such a diet are most influential.
Background
•
Patients diagnosed with cancer are highly motivated to seek
information about diet, physical activity, dietary supplement use,
and nutritional complementary therapies.1-4
•
Epidemiologic and scientific research indicates that diet and other
lifestyle factors have a significant influence on the risk of
developing colon cancer. 5,6
•
The influence of diet on colon cancer recurrences is unknown
•
Factor analysis has been used to examine overall dietary patterns,
beyond individual foods and nutrients, and the risk of several
cancers.7-8
•
Specific dietary patterns have been associated with the
development of colorectal cancer in case-control and cohort
studies.9-15
Methods
We prospectively studied dietary patterns among 1,009 patients with stage III colon
cancer enrolled in a randomized trial of post-operative adjuvant chemotherapy
(CALGB 89803), which compared bolus 5-fluorouracil and leucovorin (5-FU/LV) to
bolus irinotecan, 5-FU, and leucovorin (IFL) (Saltz et al. Proc ASCO 2004).
Patients in these analyses completed semi-quantitative food frequency
questionnaires (SFFQ) in the middle of their adjuvant chemotherapy (Q1) and
approximately 6 months after the completion of adjuvant therapy (Q2). The
questionnaire included 131 food items, vitamin and mineral supplements, and
open-ended sections for other supplements and foods not specifically listed. To
identify dietary patterns, we applied factor analysis to data from the SFFQ in each
cohort. Food items on the questionnaires were grouped into 39 predefined food
groups
Patients who completed the first SFFQ were included in these analyses. Only
patients who did not experience recurrence or die before Q1 were included in these
analyses. To avoid biases due to declining health immediately before recurrence or
death, we also excluded from analyses patients who experienced either event within
90 days following the dietary assessment. We updated dietary exposures based on
the results of the second SFFQ (Q2) using cumulative averaging, but weighted
proportional to times between Q1 and Q2 and then Q2 and disease-free survival
time.
Methods
Factor analysis (principal component) was conducted using the factor procedure in
SAS software. Factor analysis aggregates correlated variables. We retained two
factors and labeled these two factors as the "prudent" and "Western" patterns. The
prudent pattern was characterized by high intakes of fruits, vegetables, whole grains,
legumes, poultry, and fish and the Western pattern was characterized by refined
grains, processed and red meats, desserts, high-fat dairy products, and french fries.
These 2 factors are not correlated (correlation coefficient = 0.02). Factor scores
were divided into quintiles for analyses.
We computed Cox proportional hazards for recurrence-free (RFS), disease-free
(DFS) and overall survival (OS). Time intervals were measured from completion of
the 1st questionnaire to recurrence or death, excluding events within the first 90 days
to minimize potential bias from decreased activity due to underlying disease. Median
follow-up after the 1st questionnaire was 5.3 years.
We used time-varying covariates to adjust for total calories, physical activity and
body mass index with updating from Q2. Other covariates (including age at study
entry, gender, number of positive lymph nodes, baseline performance status,
presence of bowel perforation or obstruction at time of surgery, smoking history,
treatment arm, and weight change between Q1 and Q2) were also entered into the
model as fixed covariates. We tested for linear trends across quintiles of dietary
pattern by assigning each participant the median value for the quintile and modeling
this value as a continuous variable.
Derivation of Cohort Size
Figure 1: Derivation of Cohort Size
Compliance with Dietary
Questionnaire
Completed questionnaire 1
N = 1095 (98%)
Completed questionnaire 2
N = 981 (92%)
Did not complete questionnaire 2
N = 86
NOTE: To be evaluable for these
analyses, patients only had to
complete questionnaire 1.
However, if they did go on to
complete questionnaire 2 and had
calorie exclusion or more than 70
items blank, they were not
included in the analyses.
CALGB 89803
Total
Enrollment
N = 1264
Reason Inevaluable for Analyses
N = 255)
Did not complete Q1:
Enrolled prior to diet/lifestyle amendment to protocol
N = 87
Had cancer recurrence, died or was removed from
protocol treatment prior to Q1 (midway through
adjuvant therapy)
N = 59
Did not complete questionnaire 1 for other reasons
N = 23
Completed Q1 and were then excluded:
Had cancer recurrence or died within 90 days after
completion of Q1
N = 30
Calories exclusion* (outside realistic bounds) for Q1
N = 31
Left more than 70 food items blank on Q1
N=7
Completed Q2 and were then excluded:
Calories exclusion * (outside realistic bounds) for Q2
N = 15
Left more than 70 food items blank with Q2
N=3
Final Sample Size for
Dietary Pattern Study
N = 1009
Q1 = questionnaire 1
(midway through
adjuvant therapy); Q2
= questionnaire 2 (6
months after
completion of
adjuvant therapy)
* Calorie exclusion:
Less than 600
calories or greater
than 4,200 calories
per day for men and
less than 500
calories or greater
than 3,500 calories
per day for women.
Pearson correlation coefficients for the relationship between
food intake and factors representing dietary patterns
Food grouping
Vegetables †
Leafy vegetables
Yellow vegetables
Cruciferous vegetables
Legumes
Fruit
Light salad dressing
Tomatoes
Garlic
Fish
Poultry
Fruit Juice
Whole grains
Low fat mayonnaise
Wine
Tea
Diet beverages
High-fat dairy
Low-fat dairy
*
values < 0.15 are not shown (---).
Prudent
0.72
0.71
0.67
0.65
0.56
0.55
0.48
0.46
0.39
0.46
0.37
0.35
0.32
0.31
0.19
0.16
------† Vegetables
Western
-------------0.36
---------------0.67
0.64
Food grouping
Refined grains
Condiments
Red meat
Sweets and desserts
Margarine
Processed meat
Potatoes
Regular mayonnaise
Butter
French fries
Eggs
Snacks ‡
Nuts
Coffee
Sugar beverages
Beer
Cream soup or chowder
Pizza
Regular salad dressing
Liquor
other than yellow, cruciferous, or leafy-green vegetables.
Prudent
------------0.17
-----0.16
--------- 0.15
--0.16
--0.19
--‡ Potato,
Western
0.60
0.51
0.53
0.53
0.50
0.45
0.45
0.35
0.33
0.37
0.30
0.36
0.30
0.29
0.29
0.22
0.25
0.26
0.19
---
corn chips, crackers, or popcorn.
Baseline Characteristics by Quintile of Western Pattern Diet
Western Pattern
1
2
3
4
5
201
202
202
202
202
Physical activity (median MET-hours/week) at Q2
8
6.5
7.8
8.4
7.5
0.97
Male (%)
36
51
51
66
77
<0.0001
Median Age (yrs)
59
59
62
60
62
0.77
26.4
28
27
27.5
27.5
0.12
2.3
2.3
3.2
2.7
3.2
0.09
Number of Patients
Median body mass index (kg/m2) at Q1
Median Weight change (kg)
Baseline performance status (%)
PS 0
PS 1-2
Invasion through bowel wall (T stage)
T1-2
T3-4
Number of positive lymph nodes (%)
1-3 (N1)
4+ (N2)
Treatment arm (%)
5-FU/LV
IFL
Smoking Status (%)
Current
Past
Never
p value
0.85
75
25
77
23
73
27
77
23
76
24
0.27
12
88
19
81
15
85
13
87
13
87
0.24
68
32
67
33
63
37
68
32
59
41
0.25
57
43
51
49
48
52
47
53
50
50
<0.0001
4
38
58
4
51
45
9
44
47
11
47
42
13
51
36
MET = metabolic equivalent tasks; CEA = carcinoembryonic antigen; 5-FU = 5-fluorouracil; LV = leucovorin; IFL = irinotecan, 5-FU, lecovorin
Baseline Characteristics by Quintile of Prudent Pattern Diet
Prudent Pattern
1
2
3
4
5
Number of Patients
201
202
202
202
202
Physical activity (median MET-hours/week) at Q2
3.8
6.8
7.7
10.7
11.6
<0.0001
Male (%)
64
56
57
57
46
0.008
Median Age (yrs)
57
62
61
63
60
0.1
27.5
27.7
26.8
27.7
27.3
0.41
2.7
3.4
2.3
2.7
2.3
0.16
Median body mass index (kg/m2) at Q1
Median Weight change (kg)
Baseline performance status (%)
PS 0
PS 1-2
Invasion through bowel wall (T stage)
T1-2
T3-4
Number of positive lymph nodes (%)
1-3 (N1)
4+ (N2)
Treatment arm (%)
5-FU/LV
IFL
Smoking Status (%)
Current
Past
Never
p value
0.17
71
29
76
24
81
19
78
22
73
27
0.41
11
89
15
85
14
86
14
86
18
82
0.39
63
37
63
37
62
38
69
31
68
32
0.69
53
47
51
49
51
49
46
54
52
48
0.0004
16
45
39
10
48
42
7
48
45
4
49
47
4
42
54
MET = metabolic equivalent tasks; CEA = carcinoembryonic antigen; 5-FU = 5-fluorouracil; LV = leucovorin; IFL = irinotecan, 5-FU, lecovorin
Impact of Western pattern diet on
colon cancer recurrence and mortality
Quintile of Western Pattern Diet
1
Cancer recurrence or death-any cause (Disease Free Survival)
# of events / # at Risk
71/201
Multivariate adjusted hazard ratio
Ref
2
3
4
5
57/202
73/202
68/202
83/202
1.2
2.03
2.16
p value
3.91 <0.0001
(0.76-1.89) (1.30-3.16) (1.32-3.52) (2.21-6.89)
Cancer recurrence (Recurrence-Free Survival)
# of events / # at Risk
Multivariate adjusted hazard ratio
68/201
51/202
68/202
61/202
Ref
1.07
1.84
1.77
76/202
3.14 <0.0001
(0.66-1.73) (1.16-2.90) (1.06-2.95) (1.73-5.69)
Overall mortality
# of events / # at Risk
Multivariate adjusted hazard ratio
57/201
35/202
51/202
53/202
Ref
0.96
2.09
2.84
55/202
3.75 <0.0001
(0.54-1.71) (1.22-3.57) (1.56-5.05) (1.90-7.41)
* Adjusted for gender, age, depth of invasion through bowel wall (T1-2 v T3-4), number of positive lymph nodes (1-3 v 4 or more), presence of clinical
at time of surgery, presence of bowel obstruction at time of surgery, baseline performance status (0 v 1-2), treatment arm, weight change between 1st and
Impact of Prudent pattern diet on
colon cancer recurrence and mortality
Quintile of Prudent Pattern Diet
1
2
3
4
5
79/202
71/202
53/202
70/202
1.13
0.96
0.7
1.26
(0.71-1.67)
(0.63-1.46)
(0.44-1.11)
(0.80-1.97)
73/201
68/202
67/202
52/202
64/202
Ref
1.05
0.96
0.76
1.2
(0.47-1.22)
(0.75-1.94)
Cancer recurrence or death-any cause (Disease Free Survival)
# of events / # at Risk
79/201
Multivariate adjusted hazard ratio
Ref
p trend
0.79
Cancer recurrence (Recurrence-Free Survival)
# of events / # at Risk
Multivariate adjusted hazard ratio
(0.70 -1.60) (0.62-1.49)
0.76
Overall mortality
# of events / # at Risk
Multivariate adjusted hazard ratio
63/202
58/202
44/202
34/202
52/202
Ref
1.14
0.75
0.59
1.14
(0.73-1.78)
(0.44-1.29)
(0.33-1.65)
(0.81-2.45)
0.75
* Adjusted for gender, age, depth of invasion through bowel wall (T1-2 v T3-4), number of positive lymph nodes (1-3 v 4 or more), presence of clinical
at time of surgery, presence of bowel obstruction at time of surgery, baseline performance status (0 v 1-2), treatment arm, weight change between 1st and
questionnaire, time-varying body mass index, time-varying physical activity level and time-varying total calories.
Subgroup analyses by quintile of Western pattern diet
n
1
2
3
4
5
p trend
Age
p for intxn
0.59
<61 (median age)
516
Ref
> 61 (median age)
493
Ref
1.47
(0.74-2.91)
1.08
(0.56-2.07)
2.34
(1.21-4.52)
1.67
(0.89-3.14)
1.72
(0.83-3.57)
3.03
(1.50-6.14)
3.3
(1.45-7.54)
5.14
(2.28-11.60)
<0.0001
0.008
BMI
0.69
< 25 (under/normal weight)
331
Ref
> 25 (overweight / obese)
678
Ref
Gender
Male
Female
568
Ref
441
Ref
657
Ref
Higher 3 quintiles
260
Ref
IFL
1.21
(0.56-2.63)
2.43
(1.39-4.25)
1.69
(0.71-4.05)
2.42
(1.32-4.45)
2.87
(1.04-7.91)
4.1
(2.02-8.29)
0.01
<0.0001
0.66
Physical Activity
Lower 2 quintiles
Treatment arm
5-FU/LV
0.84
(0.36-1.99)
1.37
(0.78-2.40)
1.2
(0.63-2.30)
1.34
(0.69-2.62)
2.29
(1.23-4.25)
1.86
(0.94-3.69)
2.49
(1.30-4.75)
1.7
(0.75-3.87)
4.46
(2.13-3.35)
4.39
(1.68-11.42)
<0.0001
0.005
0.55
1.09
(0.61-1.95)
1.26
(0.58-2.71)
2.21
(1.25-3.91)
1.59
(0.78-3.27)
2.59
(1.34-5.01)
1.53
(0.71-3.28)
5.01
(2.40-10.5)
2.28
(0.93-5.61)
<0.0001
0.08
0.6
511
Ref
498
Ref
0.93
(0.49-1.74)
1.75
(0.87-3.69)
1.59
(0.87-2.93)
2.78
(1.39-5.59)
2.16
(1.15-4.21)
2.35
(1.09-5.07)
5.23
(2.33-11.75)
3.37
(1.61-8.68)
<0.0001
0.004
* Adjusted for gender, age, depth of invasion through bowel wall (T1-2 v T3-4), number of positive lymph nodes (1-3 v 4 or more), presence of clinical
perforation at time of surgery, presence of bowel obstruction at time of surgery, baseline performance status (0 v 1-2), treatment arm, weight change
between 1st and 2nd questionnaire, time-varying body mass index, time-varying physical activity level and time-varying total calories.
Conclusions
•
In a cohort of patients with stage III colon cancer treated with surgery
and adjuvant chemotherapy surviving without cancer recurrence 3
months after the completion of a FFQ, increasing consumption of a
Western pattern diet after diagnosis was associated with an increased
risk of cancer recurrence or death.
•
Compared to patients in the lowest level, those in the highest level of
Western pattern intake experienced a tripling in risk of recurrence or
death.
•
In contrast, prudent pattern diet did not influence the outcome after
curative resection of stage III colon cancer.
•
These data suggest that a diet characterized by higher intakes of red
and processed meats, sweets and desserts, french fries, and refined
grains increases the risk of cancer recurrence and decreases survival.
•
Further analyses are underway to better delineate specific nutrients or
food groupings that may be most influential.
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