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

Citation:

Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, Mackey JR, Koski S, Pituskin E, Sawyer MB. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res. 2009 Apr 15; 15(8) :2,920-2,926.

 
Study Design:
Prospective Cohort Study
Class:
B - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

The purpose of the study is to observe the relationship between sarcopenia or body composition and treatment toxicity of chemotherapy to further investigate clinical outcomes of metastatic breast cancer, using time to tumor progression (TTP) as a study end point.

Inclusion Criteria:
  • Women who had metastatic breast cancer
  • Had failed anthracycline and taxane treatment and were to receive capecitabine for the first time
  • Eastern Cooperative Oncology Group performance status of zero, one, two or three
  • Creatinine of less than 1.5 times the upper limit of normal
  • Aspartate aminotransferase or alanine aminotransferase of 350 IU per L or less
  • Bilirubin of 500μmol per L or less.
Exclusion Criteria:
  • Had hypersensitivity to 5-fluorouracil (5-FU)
  • Known dihydropyramidine dehydrogenase deficiency
  • Active uncontrolled bacterial or viral infections
  • Pregnant or lactating
  • Patients who did not have evaluable scans; had no scans on record or a scan more than 30 days from treatment initiation
  • Presents four thymidylate synthase enhancers genotype.
Description of Study Protocol:

Recruitment

Women undergoing treatment for metastatic breast cancer at the University of Alberta Department of Oncology, Cross Cancer Institute.

Design

Prospective cohort study.

Intervention

  • Capecitabine treatment
  • FDA-approved dosing: 1,250mg per m2 twice daily po for 14 days every three weeks
  • Alternate treatment per Oncologist: 1,000mg per m2 twice daily po. for 14 days every three weeks.

Statistical Analysis

  • Differences between two groups were assessed using Fisher's exact test and Person's χ2 test.
  • Variables known to influence TTP were entered into a multi-variate Cox proportional hazards model, with 5% confidence intervals (CI) for estimated relative risk calculated.
Data Collection Summary:

Timing of Measurements

Pretreatment

  • Albumin levels
  • Estrogen receptor status
  • Human epidermal growth factor receptor status
  • CT imaging window of ±30 days

Toxicity and Efficacy Assessment

Toxicity profile was obtained for all cycles but only first-cycle toxicities were analyzed for this study because patients who had toxicity (defined as more than grade two) had dose reductions for subsequent cycles.

Dependent Variables

  • Chemotherapy toxicity
  • Time to tumor progression.

Independent Variables

  • Sarcopenia
  • Capecitabine treatment.
Description of Actual Data Sample:
  • Initial N: 55
  • Attrition (final N): 55 (100%)
  • Age: 54.8±10.4 (37 to 80 years).

Other Relevant Demographics

Variables Mean ±SD (Range) 
BMI (kg/m2) 27±5.5 (18.2 to 46.1)
BSA (m2) 1.8±0.2 (1.4 to 2.3)
Muscle cross-sectional area (cm2) 114.2±19.5 (67.5 to 165.7)
Lumbar skeletal muscle index (cm2 per m2) 44.2±7.1 (26.4 to 59.4)
Estimated LBM (kg) 40.3±5.8 (26.3 to 55.8)

Location

Alberta, Canada.

Summary of Results:

Key Findings

Variables With Sacropenia Without Sarcopenia Statistical Significance of Group Difference

Prevalence of dose limiting toxicity

50% (N=7 of 14)

19.5% (N=8 of 41)

 P=0.039

Hazard Ratio for Toxicity

 4.1  

P=0.04

Median TTP

 		 62 days CI, 47.3 to 76.7  105 days CI, 52.3 to 157.7  P=0.05
Hazard Ratio for Shorter TTP  2.6   P=0.01
Toxicity prevalence: Stomatitis 36% 4.9% P=0.008
Toxicity prevalence:  Diarrhea  29% 2.4% P=0.01

 

Other Findings

The administered dose of capecitabine was highly variable when expressed per kg of LBM, ranging over twice (67.4 to 137mg per kg LBM). Thus patients with sarcopenia received a higher amount of capecitabine dose per unit of LBM.

Author Conclusion:

This study shows the potential need for body composition assessment to improve toxicity risk and to individualize drug dosing in a patient population with advanced cancer of the breast. Further studies should be conducted to validate drug dosing based on pre-treatment body composition and LBM analysis.

Funding Source:
University/Hospital: University of Alberta, Canada
Reviewer Comments:
  • Minimal abstracts to support diagnostic parameters for sarcopenia per CT scan of lumbar region. Potential selection bias due to utilization of primary authors personal historical data for the evaluation of LBM.
  • Nutritional status and malnutrition was not evaluated or controlled as a confounding factor, author utilized albumin which should not be an indicator for nutritional status
  • Ancillary therapies (ie, physical therapy, daily activity) not considered in controls for confounding factors
  • Study groups not comparable due to large variance in sample sizes N=14 vs. N=41.
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? ???
  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? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  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.) Yes
  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? No
  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? No
  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? N/A
  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? N/A
  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? No
  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? N/A
  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? No
  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? N/A
  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? ???
  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