ONC: Chemotherapy (2007)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

Patients with cancer are characterized by a profound impairment of glucose utilization, with lipids being the preferred fuel. In contrast, malignant tumors rely mainly on glucose as the predominant fuel.

The present study was conducted:

To examine the effects of a high-fat diet--fat-enriched commercial supplement plus a normal diet-- versus a conventional diet on the body composition of cancer patients over a period of eight weeks.

In addition, various lymphocyte subpopulations and some aspects of the quality of life were assessed in patients receiving the high-fat diet versus the conventional diet.

Inclusion Criteria:
  • Histologically proven gastrointestinal adenocarcinonomas
  • At least 3 weeks from having any major surgery
  • Had not received chemotherapy prior to study
  • Fulfilled three or more of the following five criteria with regard to malnutrtion:
    • body weight below 90 percent of the ideal value or weight loss of 10% or more during the last 6 months
    • triceps skinfold thickness less than 90 percent of the ideal value
    • arm muscle circumference less than 90 percent of the ideal value
    • creatine index below 80 percent of the ideal value and
    • serum albumin below 35 g/l  

 

Exclusion Criteria:

Patients were excluded if had

  • Insulin-dependent diabetes or other endocrine disorders
  • Liver cirrhosis
  • Renal insufficiency (creatine > 1.5 mg/dl)
  • Treatment with radiation therapy
Description of Study Protocol:

Recruitment --not discussed

 

Design -- randomized controlled trial

 

Blinding used (if applicable)--not discussed

 

Intervention (if applicable)--

Twenty-three moderately malnourished patients with gastrointestinal cancer were randomly assigned to receive either a conventional diet (Group A) or a fat-enriched commercial liquid preparation plus normal diet for 8 weeks (from the first to the third chemotherapy cycle). The initial nutritional status of the patients was assessed using anthropometric, biochemical and bioelectrical impedance (BIA) analysis. In addition, lymphocyte subpopulations were quantified and some quality of life parameters were obtained.

All patients underwent 5-days of chemotherapy consisting of 5-fluorouracil (10 mg/kg per day) and leucovucin (200 mg/day) at baseline, 4 weeks and 8 weeks.

 Nutritional Intervention

The nutrition target for both groups was an intake of 35 non-protein kcal/kg per day and 1.1 g protein/kg per day. Group B patients were assigned to receive a commercial fat-enriched drink(Pulmocare) that supplied at least 20 non-protein kcal/kg per cay; 100 ml contained 9.3 g of fat  (66% of the non-protein calories) in addition to a conventional diet.  All patients received nutritional counseling.

Nutrition counseling was avalable to both patient groups every 14 days. A four-day diet recall diary was collected from each patient in both groups in either the fifth or sixth week of the study.

Bioelectrical Impedance Analysis

Body composition measurements for patient in both groups were determined by means of a 800 µA, 50 kHz tetrapolar impedance plethysmograph (BIA) using standardized protocols. The plethysmograph separated the impedance value (Z) into its resistance (R) and reactance (Xc) components. The coefficients of variation for R and Xc were 1.1% and 2.7%, respectively.

Total body water (TBW), total body fat (TBF), fat free mass (FFM), total body mass (TBM), body cell mass (BCM), and extracellular mass (BCM) were calculated using equations by Kotler et al (1996). 

 Flow Cytometry

Lymphocyte subpopulations for patients in both groups were differentiated with a standard whole-blood assay using a commercial kit and flow cytometry.

Quality of Life

Patients in both groups were requested to rate their status in four areas: the physical, psychological, general well-being, and quality of leisure time using a linear analog self-assessment (LASA) scale. All items had test-retest reliability coefficients (r>0.60, p<0.01) 

Statistical Analysis--

  • Wilcoxon's test for matched-pairs
  • Mann-Whitney  U-test
  • Results are presented as means ± SEM.

 

Data Collection Summary:

Timing of Measurements (Group A and B):

Anthropometrics and Bioelectrical Impedance Analysis:

Patients' body weight was measured to the nearest 0.1 kg on a hospital scale. Measurement of height protocol not discussed

At baseline, total body fat (TBF, kg) and total body muscle mass (TBMM, Kg) were calculated using equations proposed by Heymsfield et al., 1984.

Body compartments were determined using bioelectrical impedance (BIA) at baseline, 4 weeks and 8 weeks. Percentage of total body water (TBW), total body fat (TBF), fat free mass (FFM), total body mass (TBM), body cell mass (BCM), and extracellular mass (BCM) were calculated using equations by Kotler et al (1996). 

Nutrition:

Nutrition counseling was provided to patients every 14 days. A 4 day diet recall diary was collected from each patient in either the 5th or 6th week of the study.

Laboratory:

Lymphocyte subpopulations were quantified with a standard whole-blood assay using flow cytometry using standardized protocol at baseline and at end of study.

Quality of Life:

Four linear analog self-assessment (LASA) scales were utilized to obtain a subjective judgement of the quality of life at baseline and at end of study.

 

Dependent Variables (Changes from baseline to weeks 4 and 8)

  • Primary:
    • Change in body weight
    • Change in body composition (fat free mass, body cell mass)
  • Secondary:
    • Lymphocyte subpopulation
    • Quality of life

Independent Variables

  •  Treatment group: Conventional diet (Group A) or high-fat liquid supplement plus normal diet

Control Variables

Not discussed

 

Description of Actual Data Sample:

Initial N: 23 (17 males, 6 females); randomized into 2 groups

Group A: 11 (8 males, 3 females)

Group B: 12 (9 males, 3 females)

Attrition (final N): not discussed

Age:

Group A--60.6 ± 3.1 y

Group B--57.8 ± 1.3 y

Ethnicity: not discussed

Other relevant demographics: not discussed

Anthropometrics

Variable Group A Group B

Body Mass Index

20.9 ± 0.7

19.6 ± 0.8

Total Body Fat (TBF), kg 12.7 ± 0.9 11.4 ± 0.9
Total Body Muscle Mass (TBMM), kg 18.3 ± 1.0

18.7 ± 0.8

Location: Germany

Summary of Results:

Nutrition:

The 4-day diet recall diaries showed that on average, Group A patients consumed 1556 ± 497 (SD) kcal/d and Group B patients consumed 1865 ± 317 kcal/d (not significant).

During both treatment periods (first 4 weeks and second 4 weeks), the consumption of non-protein calories did not differ significantly between Group A and Group B. The consumption of fat was considerably greater in group B than in Group A (data not provided). The protein content in the commercial diet was only 16.5% of the total energy.

Body Weight and Body Composition:

An average weight loss in Group A patients contrasted with an average weight gain in Group B patients after 4 (p<0.01) and 8 weeks (p<0.05)

The changes in BMI resembled those of the body weight.

There were no significant changes in total body fat observed in either patient group throughout the study. 

Fat-free mass showed an intergroup difference in favor of group B after 8 weeks (p<0.05)

There was a significant decrease in body cell mass in Group A (p<0.05 up to week 4; p<0.01 up to week 8); in contrast, BCM was maintained in Group B throughout the study

Laboratory:

The concentration of serum albumin fell significantly up to day 28 and 56 in Group A but not in Group B.

Variables
Treatment Group (Group A)
Day 28           Day 56
mean ± SEM
Control group (Group B)
Day 28           Day 56
mean ± SEM
Statistical Significance of Group Difference
Body Mass Index
-0.30±0.20    -70±0.40
0.40±0.10   0.60±0.20
Stat sign difference between groups
p<0.05
TBF, kg
 -0.84±1.00  -1.18±1.02
 1.35±1.05  0.41±0.65
 NS
 Albumin, g/l
 -2.45±1.13  -4.57±1.86*
 0.17±0.74  1.72±1.32
 

 *p<0.05

Other Findings

Total lymphocyte count remained stable in Group A but decreased by 559 cells/µl in Group B from baseline to week 8 (p 0.05)

In regard to the 4 quality of life measures, results favoring Group B were obtained.

For Group B, results for leisure activiies were more evident on day 56 than at baseline (p<0.01), compared with a slight deterioration in Group A (p<0.01).

Group B patients rated their psychological condition as being better after four and eight weeks than at baseline (p<0.05) compared with Group A.

Assessment of physical condition and general well-being tended to improve after eight weeks than at baseline, however the level was not significant (p = 0.06)

There were no significant changes in the four self-assessments of quality of life in Group A during the study.

Author Conclusion:

The results of the study suggest that a high-fat diet may be beneficial to cancer patients with regard to both body weight and body cell mass. However, the lymphocyte count needs to be monitored.

In addition, results obtained with LASA scales indicate that the four aspects of well-being that were assessed, especially the leisure activities, tended to be better in the patients receiving the high-fat diet than in the control group.

 

Funding Source:
University/Hospital: Universitat Frankfurt, Stadtisches Krankenhaus Friedrichshafen, Diakonissen-Stiftungskrankenhaus,Westpfalz=Kinikum, Universitat Heidelberg (all Deutschland)
Reviewer Comments:

Limitations of the study included:

  • Small sample size
  • Dietary information was not clear for both groups; ? carbohydrate, protein, fat
  • BIA can be reliable for longitudinal assessment of body compartments but assumes body is under normal hydration level. Factors that may affect hydration level include illness and changes in electrolyte concentrations.
  • A full instructive recommendation for assessment of quality of life was not used in this study, thus observations may not meet the comprehensive description of quality of life

 

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) ???
 
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? ???
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? ???
  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? N/A
  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? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  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? No
  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.) No
  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? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  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? ???
  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? ???
  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? ???
  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)? No
  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? No
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? No
  10.2. Was the study free from apparent conflict of interest? Yes