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

Citation:

Fearon KC, Voss AC, Hustead DS. Definition of cancer cachexia: Effect of weight loss, reduced food intake and systemic inflammation on functional status and prognosis. American Society of Nutrition. 2006; 83: 1,345-1,350.

PubMed ID: 16762946
 
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 in a homogeneous cohort of patients with cancer the role of weight loss, low food intake and the presence of systemic inflammation in a multiple factor profile of cachexia that aimed to reflect patients' adverse function and survival duration.
  • To evaluate the potential influence of these cachexia-related factors on function and prognosis in patients with different stages of disease.
Inclusion Criteria:
  • Diagnosis of unresectable pancreatic cancer
  • Weight loss of 5% or more of preillness stable weight during the previous six months
  • Karnofsky Performance Score (KPS) 60 or more
  • Life expectancy less than two months
  • Data for the three factors used in the profile for cachexia available
  • Written informed consent from patient.
Exclusion Criteria:
  • No diagnosis of unresectable pancreatic cancer
  • Weight loss less than 5% of preillness weight during the previous six months
  • KPS score less than 60
  • Life expectancy less than two months
  • Undergone surgery, endoscopic stenting, radiotherapy or chemotherapy during the previous four weeks
  • Had other active medical conditions (major gastrointestinal disease, chronic renal failure, uncontrolled diabetes and HIV)
  • Body mass index more than 30kg/m2
  • Received medication that could profoundly modulate metabolism or weight
  • Receiving systemic therapy
  • No signed written informed consent.
Description of Study Protocol:

Recruitment

  • Subjects originally recruited to a multi-center randomized controlled trial (N=200) of two different oral nutritional supplements
  • Additional details regarding recruitment were not discussed.

Design

Patient population was recruited to a multi-center randomized controlled trial of two different oral nutritional supplements. Median survival from study enrollment for all patients was 130 days and no significant difference was seen between the treatment groups  therefore for the purposes of survival analysis the treatment of patients during the follow-up period can be considered uniform. The factors used in the profile of cachexia included baseline percentage of weight loss fro usual preillness weight, baseline average daily caloric intake, and baseline C-reactive protein (CRP). Patients were followed a minimum of six months and survival was noted. 

Statistical Analysis

  • Multi-factor profile of cachexia:
    • Weight loss 10% or more from preillness usual weight
    • Food intake 1,500kcal or less per day
    • CRP concentration more than 10mg per L
  • Analyses done to compare categories for the three-factor profile, two-factor or more profile and degree of weight loss alone
  • Variable age, total caloric intake and EQ-5Dvas were analyzed with two-sample T-test
  • Remaining variables analyzed with Wilcoxon's rank sum test
  • Three-factor analysis of variance model used to examine effects of factors that make up three-factor cachexia profile on outcome variables related to body composition and functional status
  • Power of analysis limited by small number of patients in each of the eight combinations
  • Cox proportional hazards regression model fit to all variables of interest and then stepwise model was fit.
Data Collection Summary:

Timing of Measurements

  • Staging of disease completed prior to study
  • Weight, body composition, performance status, dietary intake, quality of life assessment, CA19-9 and systemic inflammation evaluated at baseline
  • Survival time in days measured from the starting point of study baseline.

Dependent Variables

  • Survival time
  • Physical function status.

Independent Variables

  • Weight loss
  • Body composition assessed by multiple frequency bioelectrical impedance analyzer
  • Grip strength assessed with hand-held spring-loaded dynamometer
  • Performance status as measured by KPS
  • Dietary intake assessed with patient completed three-day diet diary
  • Quality of life assessment measured using EuroQoL EQ-5D and respondent's assessment of overall health state
  • Systemic inflammation determined by serum CRP concentration.

Control Variables

  • Stage of disease determined by CT scan as having localized (stage II), locally advanced (stage III), metastatic (stage IV) disease
  • CA 19-9 assayed in serum by immunoassay.
Description of Actual Data Sample:
  • Initial N: 170 patients (90 males, 80 females)
  • Attrition (final N): 148 patients (77 males, 71 females)
  • Age: 67.9±9.3 years
  • Anthropometrics: Body composition, functional aspects of quality of life and inflammatory status were not significantly different in those with weight loss more than 10% than in those with weight loss less than 10%
  • Location: Multi-center trial; location not specified.
Summary of Results:

 Key Findings

  • Body composition, functional aspects of quality of life and inflammatory status were not significant in those with weight loss 10% or more than in those with weight loss less than 10%
  • KPS and grip strength were significantly lower in those with weight loss 10% or more than in those with weight loss less than 10% (P=0.013 for KPS and P=0.030 for grip strength)
  • 22% of patients met the cachexia profile definition and all quality of life function variables (P<0.001), health status (P<0.001), KPS (<0.001), grip strength (<0.001) and LBM (P=0.003) were significantly reduced in patients meeting the cachexia profile definition
  • 60% of patients met two or more of the three factors in the definition and all quality of life function variables were reduced (P<0.001) as was grip strength (P=0.02), KPS (P<0.001) and health status (P=0.01) but not LBM (P=0.063)
  • When variables entered into stepwise model for three-factor cachexia profile model, CA19-9 (HR 1.402, P<0.001), LBM (HR 1.028, P=0.018), health status (HR 0.988, P=0.017) and the three-factor cachexia profile itself (HR 2.959, P<0.001) were prognostic and results were the similar for a model in which two or more of the factors were met
  • When individual factors in the three factor cachexia profile were included, CA19-9 (P<0.001), KPS, (P=0.043) LBM (P=0.017), health status (P=0.011), food intake (P=0.004) and CRP (<0.001) carried prognostic value but not weight loss 
  • To control closely for influence of stage of disease, stepwise models were constructed by using only those patients with localized disease (stage II or III) or metastatic disease (stage IV):
    • When three-factor cachexia profile was included in the model for patients with localized disease, CA 19-9 (HR 1.35, P=0.019) and the profile itself (HR 4.94, P<0.001) were prognostic
    • When the cachexia profile model in which two or more of three factors were met for patients with localized disease was used, CA19-9 (HR 1.31, P=0.026) and the profile itself (HR 2.40, P<0.001) were prognostic
    • When individual factors were used for patients with localized disease, CA19-9 (HR 1.43, P=0.005), food intake factor (HR 2.0, P=0.01) and CRP (HR 3.74, P<0.001) carried prognostic significance
    • For patients with metastatic disease, CA19-9 (HR 1.47, P=0.007 and dyspnea (HR 1.01, P=0.025 were prognostic when either the three-factor cachexia profile or two or more of three factors in the profile were met
    • For patients with metastatic disease, only CA19-9 (HR 1.43, P=0.01) and CRP (HR 1.83, P=0.022) carried prognostic significance when individual factors of the model were used.

Other Findings

Patients had advanced disease with 46% showing evidence of distant metastases.

Author Conclusion:

Cachexia is a multi-dimensional, multi-factorial syndrome and is not synonymous with weight loss alone. A profiling system for cachexia needs to reflect such complexity, especially when considering the physical function sequelae for patients with cachexia. Inclusion of factors such as energy intake and the presence of systemic inflammation in addition to weight loss appears to provide a platform to further understanding of the important therapeutic targets for patients. 

Funding Source:
Industry:
Abbott Laboratories
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:

Ability to generalize results to all types of cancer was limited due to the study's use of only pancreatic cancer patients.

 

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? Yes
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? 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? 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? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  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? 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? 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? 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? Yes
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