ONC: Chemotherapy (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine whether changes in dietary intake, resting energy expenditure or the acute-phase response could explain changes in weight and body composition over the course of chemotherapy among patients considered to be high (non-small-cell lung cancer (NSCLC), and metastatic melanoma, and low (metastic breast) risk of wasting.
Inclusion Criteria:
  • advanced (stage III or IV) non-small-cell lung cancer (NSCLC), metastic melanoma, and metastic breast cancer patients scheduled to have chemotherapy
  • had not received any cancer therapy (e.g., surgery, chemotherapy, radiotherapy, or endocrine therapy) within 3 months prior to invitation to study
Exclusion Criteria:

Patients were excluded if:

  • had received any cancer therap (e.g., surgery, chemotherapy, radiotherapy or endocrine therapy) within the previous 3 months
  • had a prognosis of less than 2 months
  • had severe endocrine abnormalities (e.g., diabetes mellitus, or hyper/hypothyroidism)
Description of Study Protocol:

Recruitment --total of 105 patients with advanced NSCLC, 40 with metastic melanoma, and 30 with metastic breast cancer were invited to participate

 

Design --longitudinal

 

Blinding used (if applicable) --not discussed

 

Intervention (if applicable)

Prospective measurements of body mass and composition, resting energy expenditure, energy and protein intake, and C-reactive protein were obtained over a course of chemotherapy in 3 groups of patients with advanced cancer (non-small-cell lung cancer, metastic melanoma, and metastic breast cancer)

Body Mass and Composition

  • Body and FFM--determined from weight and skinfolds (triceps, triceps subscapular, suprailiac sites) using the equations of Durnin & Wormersley (1974). The coefficients of variation (CVs for the determination of fat and FFM from skinfolds on different occasions were 1.1 and 0.8%.
  • Mid-arm muscle circumference (MAMC)--calculated from tricep skinfold and mid-arm circumference using equations of Gurney & Jeliffe, 1973. CV on different occasions was 1.5%.
  • Total body potassium (TBK)--measure of lean body mass; determined using a NBR108 shadow shield whole-body monitor. Coefficient of variation of measurement was 2%.

Resting Energy Expenditure (REE)

REE was determined by indirect calorimetry (Deltratrac Metabolic Monitory) under standardized conditions. REE in 3 groups of patients were compared to age- and sex- matched healthy control subjects.

Energy and Protein Intakes

Energy and protein intakes were determined from four-day food diaries.

Inflammatory response

Serum C-reactive protein (CRP) concentration were measured using a turbidometric method. Coefficient of variation was 8.6%

Functional Status and Quality of Life

Performance status was evaluated by assigning a Karnofsky score. Quality of life was assessed by using the Functional Assessment of Cancer Therapy Scale (FACT-G).

Tumor response to chemotherapy was evaluated according to the standard criteria for melanoma, NSCLC (World Health Organization, 1979) and breast cancer patients (UICC, 1987)

 

Statistical Analysis 

Changes in outcome variables between baseline and end of chemotherapy course were determined in each of the 3 groups of advanced cancer patients using paired t-test (weight, body fat, % fat MAMC, energy intke, REE)

Pearson correlation analyses were undertaken within the 3 groups to examine relationships between mean energy intake and mean REE and changes in weight and body composition (body fat, FFM, and MAMC)

REE was predicted from the Harris Benedict equation (HB). REE for patients in 3 cancer groups were compared to age- and sex- matched healthy subjects (controls). REE was expressed in terms of kJ/24 h and % HB compared to % HB in the controls.

Energy and protein intakes were determined using a Dutch nutritional database

P < 0.05 was established for significance

Data Collection Summary:

Timing of Measurements

Measurements taken before commencing chemotherapy, prior to the second chemotherapy cycle, and 1-month post completion of chemotherapy (4-6 cycles) included:

  • Weight and skinfolds (triceps, tricep scapular, suprailiac sites). Skinfolds were measured three times by a trained individual and mean values were calculated.
  • Mid-arm circumference
  • TBK
  • REE
  • Serum CRP
  • Performance status and health-related quality of life questionnaires

Dietary

Energy and protein intakes were determined from four-day food diaries completed before each assessment in the week prior to the next chemotherapy cycle to avoid the acute effects of the treatment on dietary intake.

Dependent Variables

Change between baseline and the end of chemotherapy regimen:

  • Weight change
  • changes in resting energy expenditure and energy intake
  • change in body composition (% body fat, fat free mass (FFM), skinfolds, mid arm muscle circumference (MAMC)

Independent Variables

  • course of chemotherapy in three groups of patients: advanced NSCLC, metastatic melanoma, and metastic breast cancer 

 

Control Variables--not discussed

 

Description of Actual Data Sample:

Initial N: out of 105 patients with NSCLC, 40 patients with metastic melanoma, and 30 with metastic breast cancer;

3 groups of patients were recruited: 43 with NSCLC (28 males, 15 females); 20 with metastatic melanoma (13 males, 7 females); 19 with metastic breast cancer (all females)  

reasons for not wanting to enter study included being too ill or not wanting more visits

Attrition (final N): reassessed at end of chemotherapy: 19 with NSCLC (15 males, 4 females)--56%, 12 with metastic melanoma (9 males, 3 females)--40%; 10 with metastic breast cancer--47%

reasons for dropout: NSCLC--4 died, 12 too ill, 4 no longer wanted to attend; metastic melanoma--4 too ill, 3 no longer wanted to attend; metastic breast--6 too ill, 3 no longer wanted to attend

Age: (baseline)  NSCLC--59.5 ± 8.5y; metastatic melanoma--55.9 ± 9.2y; metastic breast cancer--52.4 ± 9.7y

Ethnicity: not discussed

Other relevant demographics: not discussed

Anthropometrics: BMI: NSCLC--24.1 ± 4.3; metastic melanoma--25.6 ± 3.0; metastic breast cancer--28.4 ± 8.5

Location: England

Summary of Results:

  advanced NSCLC   metastatic melanoma   metastatic breast cancer    
variable prechemotherapy change over chemo course prechemotherapy change over chemo course prechemotherapy change over chemo course p-value
weight (kg) 72.8  0.94  81.0  0.24  73.6  -0.3  NS
FFM (kg)  52.6  -1.1  56.2  0.6  45.7  -1.9  NS
% body fat  26.9  1.7  30.4  0.36  37.3  2.1*  0.05
MAMC (cm)  25  0.0  28.5  -1*  28  -1  0.05
TBK (counts)  1115  8.0 1252  -99  856  65  NS
REE (kJ/24 hr)  7250  -334  7217  66  5867  15  NS
Energy intake (kJ)  10439  381  7234  600  7552  974**  0.01
Protein intake (g)  98.4  -3.5  96  30  100  10**  0.01
FACT-G score  86  -3  89  0.8  91  -8*  0.05
C-reactive protein (mg)  17.5  -0.3  5  13.6  6.5  2.4  NS

  • Patients with metastic breast cancer had a significant increase in % body fat mean change (p < 0.05)
  • Patients with metastic melanoma had a significant decrease in MAMC mean (p < 0.05)
  • REE for patients with NSCLC was 112% HB compared to 97.5% in the controls (p < 0.001). REE in patients with metastic melanoma was 104% HB compared to 101% HB (NS). REE in patients with metastic breast cancer was 98.6% HB compared to 95.0% HB (NS).
  • No significant overall changes in REE within each of the 3 groups. Mean REE throughout chemotherapy did not relate to change in weight, FFM, or body fat.
  • There were significant increases in energy and protein intakes among patients with metastic melanoma and metastic breast cancer (p < 0.05)
  • Mean energy intake throughout chemotherapy was significantly related to change in weight (r = 0.603; p < 0.001) and body fat (r = 0.751; p < 0.001) among patients with NSCLC and to the change in body fat among patients with metastic breast cancer (r = 0.617; p < 0.05). Thus, gains in weight and body fat among patients with NSCLC and metastic breast cancer were related to higher energy intakes. Change in weight and body fat were not related to energy intakes among patients with metastic melanoma.
  • Change in FFM and MAMC did not relate to energy intake in any of the 3 groups.

Health Related Quality of Life

  • Patients with metastatic breast cancer had a significant decrease in FACT-G over the course of chemotherapy

Inflammatory Response

  • Among patients with NSCLC, there were negative correlations between mean CRP and change in weight, body fat, and MAMC (p < 0.05); but no relationship with change in FFM 
  • Among patients with metastatic melanoma, there was a negative correlation between mean CRP and MAMC (p < 0.05); but no relationship with change in change in weight, FFM, or body fat
  • Among patients with metastic breast cancer, mean CRP did not relate to changes in weight, body fat, MAMC, or FFM

The inflammatory response was therefore linked to loss of weight, body fat, and MAMC among patients with NSCLC; and loss of MAMC among patients with metastic melanoma

Other Findings

Within the NSCLC and metastic melanoma groups, patients assessed throughout chemotherapy were less likely to have an acute-phase protein response (APPR) at recruitment and more likely to have a favorable response to chemotherapy compared to the patients recruited to the study.

In contrast, breast metastic patients assessed throughout chemotherapy were no more likely to have an APPR than the breast cancer patients recruited to the study, but if anything appeared less likely to have a favorable response to chemotherapy.

Author Conclusion:

This study provides one of the few longitudinal assessments of energy balance (body composition, REE, dietary intake) and the systemic inflammatory response (APPR) among advanced cancer patients receiving chemotherapy. However, the high dropout rate from the study illustrates the problem of making serial measurements in such seriously ill populations.Selection bias is introduced among the patients with NSCLC and metastic melanoma because patients in whom a second measurement could be made were probably among the less seriously ill, but not apparently among those with metastic breast cancer.

Patients with metastic melanoma and metastic breast cancer had significantly higher intakes of both energy and protein over the course of chemotheraphy.

Over the course of chemotherapy,  the anticipated fall in body weight among patients with NSCLC or metastic melanoma was not found overall, but there was a range of individual nutritional responses to chemotherapy within these groups. Patients with breast cancer did not change the overall weight; but had a propensity to gain fat and to lose FFM.

The ability to meet or exceed energy requirements with NSCLC and metastic breast cancer led to gains in weight and body fat among patients with NSCLS and metastic breast cancer, but did not prevent loss of FFM in either group. The acute-phase response was linked to loss of weight and body fat among patients with NSCLC and metastic melanoma.

Funding Source:
Industry:
Scientific Hospital Supplies (UK)
Other:
Reviewer Comments:

Limitations may have included:

  • Did not assess physical activity; moderate exercise may be efficacious in the preservation of FFM
  • Small number of patients; were unable to assess whether response to chemotherapy influenced food intake, REE, body composition or APPR in each of the cancer groups. In addition,were not able to determine gender effects from analysis.
  • Very large dropout rate; concern with serial measurements in seriously ill populations
  • Selection bias among the patients with NSCLC and metastatic melanoma because patients in which a second measurement could be made were probably among the less seriously ill
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
  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
  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
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
  1. Was the research question clearly stated? Yes
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.1. 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
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? No
2. Was the selection of study subjects/patients free from bias? No
  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
  2.1. 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
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? No
  2.4. Were the subjects/patients a representative sample of the relevant population? No
  3. Were study groups comparable? No
3. Were study groups comparable? No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? No
  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
  3.3. 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? 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? No
  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
  3.5. 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
  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? No
4. Was method of handling withdrawals described? No
  4.1. Were follow-up methods described and the same for all groups? No
  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%.) N/A
  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? No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? No
  4.4. Were reasons for withdrawals similar across groups? 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
  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. 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
  5.1. 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
  5.2. 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? No
  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
  5.4. 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
  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. 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
  6.1. 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
  6.2. 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
  6.3. 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
  6.4. 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  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
  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. 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
  7.1. 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
  7.2. 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
  7.3. 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
  7.4. 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? N/A
  7.5. Was the measurement of effect at an appropriate level of precision? N/A
  7.6. Were other factors accounted for (measured) that could affect outcomes? No
  7.6. Were other factors accounted for (measured) that could affect outcomes? No
  7.7. Were the measurements conducted consistently across groups? 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. 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
  8.1. 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
  8.2. 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
  8.3. 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
  8.4. 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
  8.5. 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
  8.6. 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
  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. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? 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. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes
  10.2. Was the study free from apparent conflict of interest? Yes