Oncology

ONC: Nutrition Status and Outcomes in Adult Oncology Patients (2013)

Citation:

Yoon H, Lewis M, Shi Q, Khan M, Cassivi S, Diasio R, Sinicrope F. Prognostic impact of body mass index stratified by smoking status in patients with esophageal adenocarcinoma. J Clin Oncol. 2011; 29: 4,561-4,567.

 
Study Design:
Retrospective Cohort Study
Class:
B - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To measure the relationship of obesity on survival from gastroesophageal junction (GEJ) and gastric cardia, collectively referred to as esophageal adenocarcinoma (EAC), after stratification by smoking status. 

Inclusion Criteria:
  • Adult patients, both men and women
  • Patients newly diagnosed adenocarcinoma of the esophagus, GEJ or gastric cardia who underwent surgical resection with cancer-free margins at Mayo Clinic in Rochester Minnesota between January 1, 1980 and December 31, 1997. 
Exclusion Criteria:

  • Sub-cardial gastric cancers and tumors with non-adenocarcinoma histology
  • Patients receiving neoadjuvant chemotherapy and radiotherapy (N=9)
  • Underweight as measured by BMI less than 18.5kg/m2 (N=9).

 

Description of Study Protocol:

Recruitment

Study cohort is from larger Mayo Esophageal Cancer Outcomes Database.

Design

  • At time of esophagectomy, height and weight were measured on all subjects
  •  Within the two weeks prior to surgery, patients completed a survey assessing current and past cigarette smoking as well as weight history
  • The responses to the surveys were verified by their primary care physician during a visit to the Mayo clinic.

Statistical Analysis

  • Kaplan-Meier and Cox proportional hazards models were used to assess the association between predictor variables and outcomes
  • Wilcoxon rank sum and Χ2 tests were used to compare continuous and categorical variables between groups, respectively
  • To assess whether the effect of BMI on DSS was modified by smoking status, as interaction term [i.e., the product of categorical BMI and smoking status (ever vs. never)] was included in the Cox model in addition to BMI and smoking status
  • The primary multivariate Cox model included tumor stage and grade (American Joint Committee on Cancer criteria, 7th edition, 2009)
  • Age, sex and pre-surgery weight loss (10% or more) were added to subsequent models; given that the results were highly stable, multivariate models containing all covariates are reported
  • For ever smokers, number of pack-years was also includes as indicated
  • Hazard ratios (HRs) with 95% CIs and two-sided P-values were reported. P≤0.05 was considered statistically significant.
  • Analyses were conducted in SAS version 9.1 (SAS Institute, Cary, NC).
Data Collection Summary:

Timing of Measurements

  • Height and weight were measured at time of surgery
  • Smoking and weight history were assessed during the two-week period preceding surgery
  • Death beyond five years was censored.

Dependent Variables

  • Variable one: Disease-specific Survival (DSS) included time from surgery to death related to EAC
  • Variable two: Disease-free survival (DFS) included time from surgery to the first recurrence of index cancer or to all-cause death
  • Variable thee: Overall survival (OS) included the time from surgery to death resulting from any cause.

Independent Variables

  • BMI
  • Smoking status.
Description of Actual Data Sample:
  • Initial N: 796
  • Attrition: 778 (692 males, 86 females)
  • Age: Median age 65 years (range 22 to 89 years).

Anthropometrics

BMI: 

  • Obese 171 (22%)
  • Overweight 348 (45%)
  • Normal 259 (33%).

Location

Rochester, Minnesota, US.

Summary of Results:

 Key Results

  • Past studies have shown that excess BMI increases risk of developing EAC
  • This study found that excessive BMI was significantly associated with Disease-Specific Survival (DSS), but the manner was different for never smokers vs. ever smokers
  • For never smokers, obesity was significantly associated with adverse DCC
  • For ever smokers, obesity was not prognostic and overweight status was significantly associated with favorable survival with some statistical analysis (univariate, not multivariate).

Baseline Characteristics at Surgery by Smoking Status in Patients with Esophageal Adenocarcinoma

  Overall (N=778) Never Smokers (N=236) Ever Smokers (N=542) P
  No.

%

No. % No. %  

Sex

Male

Female

 

692

86

 

 89

11

 

192

44

 

81

19

 

500

42

 

92

8

 <0.001

Age

Median

Range

 

65

22 to 89

 

68

22 to 89

 

64

30 to 88

 <0.001

Stage

IIIC

IIIB

IIIA

IIB

IA to IIA

 

127

173

160

144

156

 

17

23

21

19

20

 

38

56

40

55

44

 

16

24

17

24

19

 

89

117

120

89

112

 

17

22

23

17

22

0.138

Grade

Four

One to three

 

300

467

 

39

61

 

84

150

 

36

64

 

216

317

 

41

59

0.225

Weight Loss*

10% or more

10% or less

 

174

604

 

22

78

 

60

176

 

25

75

 

114

428

 

21

79

0.177

Body Mass Index

Obese

Overweight

Normal

 

171

348

259

 

22

45

33

 

46

117

73

 

19

50

31

 

125

231

186

 

23

43

34

0.192

*In the year preceding surgery.

Disease-Specific Survival According to Clinopatholigic Variables in Univariate and Multivariate Analysis Among Never Smokers (N=236)

  Univariate Multivariate
  HR 95% CI P HR 95% CI P

Sex

Male

Female

 

1.57

Ref

1.00 to 2.47 0.049

 

1.25

Ref

0.76 to 2.05

0.370
Age, per year increase 1.00

 0.99 to 1.02

0.841  1.01 0.99 to 1.02  0.378

Stage

IIIC

IIIB

IIIA

IIB

IA to IIA

 

 

14.16

10.55

7.96

3.96

Ref

6.73 to 29.81

5.11 to 21.79

3.81 to 16.64

1.8 to 8.3

<0.001

<0.001

<0.001

0.0003

 

11.98

11.19

7.57

4.12

Ref

5.6 to 25.63

5.32 to 23.54

3.59 to 15.98

1.96 to 8.66

<0.001

<0.001

<0.001

0.002

Grade

Four

One to three

 

1.61

Ref

1.17 to 2.22 0.0038

 

1.17

Ref

0.83 to 1.65

0.374

Weight loss*

10% or more

10% or less

 

1.68

Ref

 1.19 to 2.38 0.0035

 

1.38

Ref

0.96 to 1.99 0.081

Body Mass Index

Obese

Overweight

Normal

 

1.62

1.17

Ref

 

1.03 to 2.53

0.81 to 1.71

 

0.034

0.403

 

2.11

1.27

Ref

1.31 to 3.43

0.86 to 1.88

0.0023

0.231

*In the year preceding surgery.

Survival According to Body Mass Index Stratified by Smoking Status in Multivariate Models Adjusted for Age, Stage, Grade, Weight Loss and Sex (N=778)

    Disease-specific Survival    Disease-free Survival    Overall Survival   
BMI No. Event-Free Rate, % HR 95% CI P Event-Free Rate, % HR 95% CI P Event-Free Rate, % HR 95% CI P

Never Smokers (N=236)

Obese

Overweight

Normal

 

 

46

117

73

 

 

18

32

36 

 

 

2.11

1.27

 

 

 

1.31-3.43

0.86-1.88

Ref

 

.002

NS

 

 

15

28

28

 

2.03

1.16

 

 

1.30-3.18

0.81-1.67

Ref

 

.002

NS 

 

 

17

30

32

 

1.97

1.17

 

 

1.24-3.14

0.81-1.70

Ref

 

.004

NS

Ever Smokers (N=542)

Obese

Overweight

Normal

 

 

125

231

186 

 

 

33

39

28 

 

0.90

0.78 

 

 

0.67-1.20

0.61-1.02

Ref

 

NS

NS 

 

 

27

34

23

 

1.00

0.87

 

 

0.76-1.33

0.68-1.11

Ref

 

NS

NS

 

 

30

37

26

 

0.90

0.80

 

 

0.68-1.20

0.62-1.02

Ref

 

NS

NS 

 

 

Author Conclusion:
  • Obesity is independently associated with increased mortality among never smokers
  • This association is not found with ever smokers
  • The biological mechanisms underlying the interaction between smoking and obesity awaits further study
  • The findings from this study are relevant to patient management as they can provide prognostic information that can inform post-operative risk stratification.
Funding Source:
University/Hospital: Mayo Clinic
Reviewer Comments:

Attrition was very low.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) N/A
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? ???
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? ???
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? ???
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes