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

Citation:

Tan BH, Birdsell LA, Martin L, Baracos VE, Fearon KC. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res. 2009 Nov 15; 15(22): 6,973-6,979.

PubMed ID: 19887488
 
Study Design:
Prospective Cohort Study
Class:
B - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To evaluate if weight and body composition, specifically sarcopenia, assessed from diagnostic computed tomography (CT) scans, is of prognostic value in patients with pancreatic cancer.

Inclusion Criteria:
  • Referred to the regional cancer center in Edmonton, Alberta, Canada from January 2004 to October 2008
  • Primary diagnosis of pancreatic cancer entering a palliative program who had an abdominal CT scan within 60 days of initial assessment.
Exclusion Criteria:
  • Ampullary carcinoma
  • Cholangiocarcinoma
  • Neuroendocrine tumors.
Description of Study Protocol:

Recruitment

  • All patients referred to the regional cancer center in Edmonton, Alberta, Canada from January 2004 to October 2008 were considered for the study.
  • Patients with a primary diagnosis of pancreatic cancer entering a palliative program who had an abdominal CT scan within 60 days of initial assessment were selected for the study.

Design

  • Coding of the primary cancer by its site and morphology, clinical information and demographic information were obtained from the Alberta Cancer Registry for every patient in the cohort. The Alberta Cancer Registry is a computerized database of all cancer cases in the region (population 1.8 million). Patient-reported height, weight and weight history were collected during this visit by use of the Patient-Generated Subjective Global Assessment. Height and weight data were subsequently used to compute  BMI (kg/m2). Height and weight recorded by hospital staff on the same date were used for verification where available, and classification of patients' BMI with the use of patient-reporting was found to be accurate. Patient-reported height, weight and weight history have been shown to be reliable. Stage of disease was based on the American Joint Committee on Cancer stage groupings I, II, III, and IV.
  • From the initial cohort of 111 patients, 44 patients were further identified who:
    • Had had at least one further follow-up CT scan
    • Had a documented duration of survival for inclusion into the study of longitudinal changes of body composition. 
  • Cutoffs for sarcopenia were based on a CT-based sarcopenic obesity study of cancer patients by Prado et al. (i.e., L3 skeletal muscle index: 38.5cm2 per m2 or less for women and 52.4cm2 per m2 or less for men)
  • Patients were then divided into four groups:
    • Neither sarcopenic nor overweight/obese
    • Overweight/obese
    • Sarcopenic
    • Both sarcopenic and overweight/obese. 

Statistical Analysis

  • Survival was determined from the time of initial assessment until death or until the censor date of January 5, 2009
  • Univariate and multivariate survival analyses and calculation of hazard ratios were done using a Cox regression model. Owing to the large number of covariates examined, only those that were significant on univariate analysis were included in multivariate analysis. Receiver-operator characteristic curves were used to select cutoff values for continuous variables. Values with the best combination of sensitivity and specificity were chosen. A backward stepwise procedure was done to derive a final model of the variables that had a significant relationship with survival. To remove a variable from the model, the corresponding P value had to be more than 0.05.
  • Comparisons between groups of patients were assessed using one-way ANOVA or Pearson's χ2 test. Survival curves were constructed using the Kaplain-Meier technique. Log-rank test was used to compare survival between groups of patients. Comparison of data at different time points for body composition analysis was done using the paired T-test.
Data Collection Summary:

Timing of Measurements

Abdominal CT scan was completed within 60 days of initial assessment.

Dependent Variables

Survival.

Independent Variables

Sarcopenia.

Control Variables

Type of cancer.

Description of Actual Data Sample:
  • Initial N: 111 (52 male, 59 female)
  • Attrition (final N): 111 and then 44 of this initial sample had either at least one further follow-up CT scan or had a documented duration of survival for inclusion into the study of longitudinal changes of body composition
  • Age: 64.4±9.3 years.

Other Relevant Demographics

Anthropometrics Number Percentage
BMI (kg/m2) Mean ±SD
23.9±4.9
 
  Underweight (BMI less than 18.5kg/m2)
11
9.9
  Normal (BMI 18.5kg/m2 to 24.9kg/m2)
56
50.5
  Overweight/obese (BMI 25kg/m2 or more)
44
39.6
Percentage weight loss (in preceding six months)
12.14±6.35
 
Sarcopenic
62
55.9
Overweight/obese and sarcopenic
18
16.2
Status Dead
101
91.0
Alive
10
 

Location

Edmonton, Alberta, Canada.

Summary of Results:

Comparison of Demographic Characteristics and Body Composition of Patients Who Were Neither Overweight nor Sarcopenic, Sarcopenic Alone, Overweight Alone and Both Overweight and Sarcopenic

 
BMI Less Than 25kg/m2
BMI 25kg/m2 or More
 
Not Overweight, Not Sarcopenic (N=23; 21%)
Not Overweight, Sarcopenic (N=42; 38%)
Overweight/Obese (N=28; 25%)
Overweight/Obese and Sarcopenic (N=18; 16%)
Age, years (mean±SD)
60.7±7.5
65.8±10.2
64.3±9.0
66.0±9.3
0.169*
Sex, N (%) Male
8 (34.8)
20 (47.6)
11 (39.3)
13 (72.2)
0.084
Female
15 (65.2)
22 (52.4)
17 (60.7)
5 (27.8)
 
Tumor site, N (%) Head
8 (34.8)
26 (61.9)
14 (50.0)
9 (50.0)
0.088
Body
9 (39.1)
3 (7.1)
4 (14.3)
2 (11.1)
 
Overlapping lesion
3 (13.0)
3 (7.1)
2 (7.1)
3 (16.7)
 
Histology, N (%) Adenocarcinoma
18 (78.3)
28 (66.7)
22 (78.6)
16 (88.9)
0.287
Stage, N (%) IV
20 (87.0)
37 (88.1)
28 (100)
18 (100)
0.149
BMI (kg/m2)
22.2±1.9
20.5±2.8
27.6±2.7
28.5±6.3
<0.0001*
% Weight loss
12.83±5.80
13.08±6.45
11.36±6.72
10.45±6.24
0.435*
Lumbar total muscle cross-sectional area (cm2)
129.5±31.8
115.0±29.2
138.5±29.6
128.0±27.6
0.014*
Lumbar total adipose tissue cross-sectional area (cm2)
185.0±137.7
168.8±130.6
344.2±148.0
348.6±155.1
<0.0001*
Lumbar skeletal muscle index (cm2 per m2)
46.2±7.1
39.3±6.2
49.4±7.3
42.7±6.6
<0.0001*
Lumbar adipose tissue index (cm2 per m2)
68.4±52.3
57.6±42.0
125.6±55.7
117.1±50.7
<0.0001*
Estimated total fat-free mass (kg)
44.9±9.5
40.6±8.8
47.6±8.9
44.5±8.3
0.014*
Estimated total fat mass (kg)
19.0±5.8
18.3±5.5
25.7±6.2
24.2±7.7
<0.0001*

* P level one-way ANOVA.

† P level Pearson's X2 test.

Other Findings

Median survival for patients who were both overweight or obese and sarcopenic was 55 days (IQ range, 43 to 207 days) compared with 148 days (IQ range, 80 to 369 days) for the rest of the patient cohort without overweight/obese sarcopenia (log-rank test, P=0.003;). Using receiver-operator characteristic curves, the cutoff value with the best discriminatory value for age was 59 or more years. On multivariate analysis, age 59 years or more (HR, 1.71; 95% CI: 1.10 to 2.66; P=0.018) and overweight/obese sarcopenia (HR, 2.07; 95% CI: 1.23 to 3.50; P=0.006) retained independent prognostic value.

 

 

Author Conclusion:

Sarcopenia in overweight/obese patients with advanced pancreatic cancer is an occult condition but can be identified using CT scans. This condition is an independent adverse prognostic indicator that should be considered for stratification of patients' entering clinical trials, systemic therapy or support care programs. 

Funding Source:
Government: European Commission grant, Canadian Institutes of Health Research Grants
Reviewer Comments:
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) Yes
  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) Yes
 
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? N/A
  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? Yes
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  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? Yes
  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? Yes
  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? Yes
  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.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  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? No
  6.6. Were extra or unplanned treatments described? No
  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)? Yes
  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? N/A
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