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

Citation:

Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: A population-based study. Lancet Oncol. 2008; 9(7): 629-635.

PubMed ID: 18539529
 
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 assess the prevalence and clinical implications of sarcopenic obesity (obesity with depleted muscle mass) in patients with cancer.

Inclusion Criteria:
  • Cancers of the respiratory tract, colorectum and other gastrointestinal locations (anus, pancreas, stomach, esophagus)
  • Obesity (BMI 30 or higher)
  • Assessable CT images, taken within 30 days of the BMI assessment.
Exclusion Criteria:
  • Cancers other than those of the respiratory tract, colorectum or other gastrointestinal locations
  • Non-obese (BMI less than 30)
  • No assessable CT scans (patients had no scans on record, a scan over 30 days from the assessment date, L3 not included in the scan or their larger size meant that they did not fit in the scanner or had a substantial part of their images cut off).
Description of Study Protocol:

Recruitment

A computerized database at the Alberta Cancer Board (Edmonton, AB, Canada) documents information on all primary cancers by their body site and morphology and provides corresponding biological, clinical and demographical information for each patient. The population included all new patients referred to medical oncology clinics at the Cross Cancer Institute between Jan 13, 2004, and Jan 19, 2007, for treatment. Patients were classified as obese or non-obese on the date of their first visit to the clinic. Obese patients with assessable CT images were included in the final analysis. Written informed consent was not needed.

Design

Prospective cohort study.

Intervention

Available lumbar CT images of the obese patients were analyzed. Statistical analysis was used to establish relationship between sarcopenic obesity and its clinical implications such as functional status, survival and potential chemotherapy toxicity.

Statistical Analysis

  • Optimum stratification analysis was used to find the most significant P value by use of the log-rank Χ2 statistic to define the sex-specific cut-offs associated with mortality. These cut-offs were then used to classify patients as those with sarcopenia or those who without.
  • Comparisons between these two groups were assessed by use of Fisher's exact test and Pearson's Χ2 test. All tests were two-sided and significance was reported at the P<0.05 level.
  • Univariate and multivariate survival analyses included the major established predictors of outcome of advanced cancer. The Kaplan-Meier method was used to establish the effect of each variable on survival. Log-rank tests were used to compare the survival curves of each variable. Variables known to affect survival were entered into a multivariate Cox proportions hazards model, and 95% CIs for the estimated hazard ratios (HRs) were calculated.
  • Regression equations relating muscle area in the lumbar region with total body fat-free mass were used to estimate total body fat-free mass from muscle cross-sectional area.
Data Collection Summary:

Timing of Measurements

Patients were classified as obese or non-obese on the date of their first visit to the clinic. Patient-reported height, weight, weight history and functional status were collected during this visit. Each patient's record was reviewed for CT images taken within 30 days of the BMI assessment. Data were collected prospectively and patients were followed up until death.

Dependent Variables

  • Lumbar muscle cross-sectional area (measured by secondary analysis of electronically stored CT images)
  • Lumbar skeletal muscle index (computed by using area of total L3 skeletal muscle normalized for stature)
  • Estimated total body fat-free mass (estimated from muscle cross-sectional area using regression equations)
  • Muscle attenuation [skeletal muscle was quantified by use of Hounsfield unit (HU) thresholds (-29 to +150)]
  • Cancer site
  • Stage of cancer [based on the Tumor, Nodes, and Metastasis (TNM) staging system]
  • Functional status [(by use of the Patient-Generated Subjective Global Assessment (PG-SGA)]
  • Body surface area (computed by use of the Mosteller formula)
  • Weight change (in preceding six months).

Independent Variables

Presence or absence of sarcopenic obesity.

Control Variable

  • Age
  • Sex.
Description of Actual Data Sample:

Initial N

  • 250: 136 males, 114 females
  • Obese patients with sarcopenia: (N=38): 28 males, 10 females
  • Obese patients without sarcopenia (N=212): 108 males, 104 females.

Attrition (final N)

250.

Age

63.9±10.4 years (range 35 to 88 years).

Anthropometric

No separate BMI data for the two groups.

 

Men
(N=136)

Women
(N=114)

Total
(N=250)
Body mass index    Mean (SD)
33.9 (4.4)
34.7 (4.3)
34.3 (4.4)
Range
30.0 to 52.7
30.0 to 55.0
30.0 to 55.0

Location

Cross Cancer Institute, Edmonton, AB, Canada.

 

Summary of Results:

Key Findings

  • Of the 2,115 patients initially identified, 325 (15%) were classified as obese. Of these obese patients, 250 had CT images that met the criteria for analysis.
  • Obese patients had a wide range of muscle mass
  • Sex-specific cut-offs that defined a significant association between low muscle mass with mortality were ascertained by optimum stratification analysis. 38 (15%) of 250 patients were below these cut-offs and were classified as having sarcopenia.
  • Mean muscle cross-sectional area, L3 skeletal muscle index, and estimated total body fat-free mass were different between the two groups. Muscle attenuation was lower in obese patients who had sarcopenia.
 
 		 Obese Patients with Sarcopenia
(N=38)		 Obese Patients Without Sarcopenia
(N=212)		 P
 
Lumbar muscle cross-sectional area (cm2)   
   Mean (SD) 128.1 (29.1) 160.0 (38.1) <0.0001
   Range 79.2 to 184.8 95.6 to 271.5  
Lumbar skeletal muscle index (cm2 per m2)   
   Mean (SD) 43.3 (6.3) 56.4 (9.9) <0.0001

   Range

 29.8 to 52.3 38.5 to 91.4  
Estimated total body fat-free mass (kg)   
   Mean (SD) 44.5 (8.7) 54.1 (11.4) <0.0001
   Range 29.8 to 61.5 34.7 to 87.5  
Muscle attenuation (HU)   
   Mean (SD) 22.8 (8.5) 30.6 (7.8) <0.0001

 

  • Sarcopenic obesity was more prevalent in male patients compared with female patients (P=0.013), in those who had colorectal cancer compared with other cancer sites (P=0.019) and in patients aged 65 years or older compared with younger patients (P=0.008) but independent of TNM stage and history of previous weight loss
  • Sarcopenic obesity was associated with poorer functional status. 18 (47%) of the 38 obese patients with sarcopenia reported poorer functional status compared with 56 (26%) of the 212 obese patients who did not have sarcopenia (P=0.009).
  • Significant discriminates for survival by univariate analysis included functional status, sarcopenia and cancer diagnosis and stage. When these factors were modeled by use of a multivariate Cox proportional hazards model, sarcopenic obesity was shown to be a significant independent predictor of survival. Survival was about 10.0 months shorter for patients with sarcopenic obesity.
  Multivariate analysis  
  Coefficient (SE) Hazard ratio (95% CI) P
Sarcopenic obesity1 1.42 (0.23) 4.2 (2.4 to 7.2) <0.0001
Functional status score2 0.92 (0.20) 2.6 (1.7 to 3.7) <0.0001
Respiratory tract cancer3 1.35 (0.26) 3.9 (2.3 to 6.4) <0.0001
Other cancer diagnosis3 0.94 (0.27) 2.6 (1.5 to 4.4) 0.001
Stage IV cancer4 1.25 (0.41) 3.5 (1.6 to 7.8) 0.002

1Vs. obese patients without sarcopenia. 2Vs. patients with functional status scores zero to one. 3Vs. patients with colorectal cancer. 4Vs. stage one cancer.

  • Estimated fat free mass (FFM) showed a poor association with body-surface area (R2=0.37). It was estimated that individual variation in FFM could account for up to three times in variation in effective volume of distribution for chemotherapy administered per unit body-surface area in this population.
Author Conclusion:
  • Cancer patients with sarcopenic obesity had exceptionally lower functional status and their sarcopenia was an independent risk factor for poor survival, highlighting the importance of uncovering a means of treating sarcopenia and of routine body composition assessment for risk stratification in a clinical oncology setting
  • An apparently large bodyweight might mask sarcopenia. Men, patients aged over 65 years and those affected by colorectal cancer seem to be especially susceptible to sarcopenia.
  • Body composition variability might introduce a variation of drug volume of distribution. If variation in toxicity can be partially explained by features of body composition, identification of clinical measure of body composition for a more refined delivery of chemotherapy dose is important.
Funding Source:
Government: Canadian Institutes of Health Research (Ottawa, ON, Canada), Translational Research Training in Cancer (Edmonton, AB, Canada)
Not-for-profit
Alberta Cancer Board (Edmonton, AB, Canada)
Reviewer Comments:
  • 75 out of 325 obese patients were without assessable scans. Some patients were too obese to fit in the scanning machine, so data could not be obtained.
  • No blinding was described but bias was unlikely since all measurements were based on objective tests or patient reported data
  • The prevalence of obesity is very difficult to confirm because of the prevalence of involuntary weight loss in patients with cancer
  • A number of patient-reported data were used in this study, although they were shown to be consistent with results from direct measurements and performance-based tests.
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? 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? N/A
  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? No
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  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? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  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.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? ???
  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? N/A
  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)? 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? 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