EAL

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: 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)

No.

Sex

Male

Female

692

192

500

<0.001

Age

Median

Range

22 to 89

30 to 88

<0.001

Stage

IIIC

IIIB

IIIA

IIB

IA to IIA

127

173

160

144

156

117

120

112

0.138

Grade

Four

One to three

300

467

150

216

317

0.225

Weight Loss*

10% or more

10% or less

174

604

176

114

428

0.177

Body Mass Index

Obese

Overweight

Normal

171

348

259

117

125

231

186

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, %

95% CI

Event-Free Rate, %

95% CI

Event-Free Rate, %

95% CI

Never Smokers (N=236)

Obese

Overweight

Normal

117

2.11

1.27

1.31-3.43

0.86-1.88

Ref

.002

2.03

1.16

1.30-3.18

0.81-1.67

Ref

.002

1.97

1.17

1.24-3.14

0.81-1.70

Ref

.004

Ever Smokers (N=542)

Obese

Overweight

Normal

125

231

186

0.90

0.78

0.67-1.20

0.61-1.02

Ref

1.00

0.87

0.76-1.33

0.68-1.11

Ref

0.90

0.80

0.68-1.20

0.62-1.02

Ref

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