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ONC: Chemotherapy (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The authors purported that men with nonsmall cell lung cancer  were more susceptable to weight loss than were women. The composition and etiology of the gender specific weight changes are examined through:

  • Measuremnt of body mass
  • Measurement of body composition
  • Measurement of energy balance(resting energy expenditure  and energy intake).

 

Inclusion Criteria:
The inclusion criteria was not detailed.
Exclusion Criteria:
Those patients with a prognosis of < 2 months or endocrine abnormalities(e.g. diabetes mellitus or hyper/hypothyroidism) were excluded.
Description of Study Protocol:

Recruitment : A total of 112 patients newly daignosed with advanced NSLC(stag III or IV) and scheduled to have chemotherapy were invited to enter the study. Fifty patienst were recruited. The remaining 62 did not wish to enter the study ;48% were too ill and 42% did not want an additional hospital appointments.

 

Design -Within subjects(repeated measures)design. The same subjects were used for each level of the independent variable,as in before-after studies or panel studies.

 

 

Blinding used (if applicable)

 

Intervention -the chemotherapy was not detailed in the study.

 

Statistical Analysis : Paired t-test or Wilcoxin tests were used to analyze the changes in nutritional parameters between baseline and the end of chemotherapy. The p-values reported were corrected for the Bonferroni adjustment to allow for the multiple testing.

 

Data Collection Summary:

Timing of Measurements

Patients were seen both prior and 1 month after the end of chemotherapy. At each occasion:

  • body fat and fat free mass(FFM) were determined
  • Skinfolds were measured three times on each occasion
  • Resting Energy Expenditure(REE) was measured following an over night fast .

 

 

Dependent Variables

1.  Weight(kg) /fat free mass-determined from weight and skinfolds(bicepts,tricepts,subscapular and suprailiac)using the equations of DurninWormsley(1974).

  • Skinfolds were measured three times on each occasion by a trained individual(MH),and the mean values were calculated. There was no overt edema observed in skinfolds.
  • The coefficient of variation for the determination of fat  and FFM by skinfolds measured by MH on different occasions were respectively,1.1 and 0.8%.

2. Energy intake was assessed from 4-day weighed food diaries using Compeat 4 Nutrition Analysis System(Carlson Bengston Consultants,London,UK) based on the fifth edition of McCance and Widowson.

  • The Composition of Foods  publication was utilized(Holland et al.,1991)
  • REE was measured following an overnight fast using indirect calorimetry(Deltatrac Metabolic Monitor,Datex,Finland).
  • Values are expressed as a percentage of REE predicted from Harris Bendict equation(Harris and Benedict,1919) to standardize for age, height, and weight.

3. C-reactive protein was measured using a turbidometric method (Dako Patts,Copenhagen,Denmark).

Independent Variables

  • Age(years)
  • Weight changes over the previuos six months
  • Body Mass index(kg/m2 )
  • Smoker
  • Stage of disease- Localized ; metastatic
  • Histology-adenocarcinoma,squamous cell,large cell
  • Response to chemotherapy-tumor response,stable disease,progressive disease

 

Control Variables

 

Description of Actual Data Sample:

 

Initial N: Fifty(50)  of the 112 invited patients were recruited; this included 32 men and 18 women.

The group of men and women were comparable in terms of age,body mass index,recent weight loss ,and tumor response. There was a higher incidence of adenocarcinoma in the women and squamous cell carcinoma in men(p<0.01). A greater proportion of women had metastatic  disease(p<0.01). The mean length of chemotherapy was 5 months amongst men compared with 4.2 months in women.

Table I Characteristics of men and women with NSCLC assessed throughout chemotherapy
 

Male(N=15)

 Female(n=6)
Age(years)

58.6±(6.2)*

59(8.1)

Weight change over the previous 6 months(%)

 

-6.5

(-18 to 3.o)**

-11

(-14 to 0)
Body mass index(kg/m2

25.3(3.8)

24.3(6.1)
Smoker

40%

50%
Stages of disease    
Localized/metastic §

 

12:3

2:4
Histology

 

 
Adenocarcinoma

3

5
Squamous cell

11

1
Large cell

1

  
Response to chemotherapy¶    
Tumor response

5

2
Stable disease

2

1
Progressive disease

8

3

*Mean(SD) ** Median(range) 

§Localized=stage 111a/111b

Metastatic=stage IV(Mountain,1997)

¶ WHO(1979)

 

 

Attrition (final N): 15 men and 6 women

  • 4 patients died(2 men;2 women)
  • 12 patients were too ill to attend(8 men;4 women)
  • 7 patients  who received radiotherapy or best supportive care, not chemotherapy(5 men;2 women)
  • 6 patients did not wish to attend(2 men;4 women)

Age: ( mean/(standard deviation) :Males =58.6(6.2); Females 59.8(8.1)

Ethnicity: not detailed

Other relevant demographics:

Anthropometrics

Location: University Department of Anaesthesia,Medical Oncology and Surgery,South Manchester University Hospitals NHS Trust,Manchester,UK.

 

Summary of Results:

Changes in nutritional parameters over the course of chemotherapy are detailed in Table 2. Minimal weight change was observed in both men and women. Men had a significant increase in % body fat(P<0.05) and a tendency for FFM to decrease(P=0.063). Both FFM  and fat remained unchanged in women. Men experinced a significant decline in REE (P<0.05)whereas REE in the women was maintained. The were no changes in C-reactive protein in either group.

Table 2:Changes in nutritional parameters over the course of chemotherapy in men and women with NSCLC.  

 

 

   Male (n=15)

  ⇒  ⇒ ⇒  ⇒  ⇒

Female(n=6)  

 ⇒⇒⇒⇒⇒⇒⇒⇒
  Baseline      Post-chemotherapy Baseline Post-chemotherapy
Weight(kg) 77.7(15.5)*     78.2(15.1)  63.5(20)

 62.8(18)
 Fat free mass(kg)  57.6(9.2)  55.6(8.6)  40.8(8.0)  41.4(8.2)
 Total fat (kg)  20.0(7.3)  22.9(9.2)  22.2(11.3)  21.4(10.3)
 % Body fat  25.0(5.5)  27.9(7.9)¶  33.7(6.7)  32.5(6.5)
C-reactive protein(g/l)

 32(5-182)**

  9(5-222)  19(5-105)  24(5-71)
REE(kcal)  1934(342)  1806(263)  1289(218)  1311(307)
REE % Harris Benedict  113.2(15.9)  105.1(10.0)¶  104.2(17.1)  104.6(16.8)
Energy Intake(kcal)  2733(822)  2713(952)  2014(723)  1902(335)

 

 *Mean (SD);** median(range). ¶ Significant difference between pre and post-chemotherapy with Bonferroni adjustment(p<0.05). REE,resting enegy expenditure.

Other Findings

 

Author Conclusion:
  • Over the course of chemotherapy for NSCLC ,men and women appear to have different patterns or changes  in both body composition and energy expenditure.
  • Loss of fat free mass in this apparently weight stable population of men with NSCLC re-iterates the importance of monitoring body weight composition as well as weight in cancer patients
  • Loss of fat free mass appears to be resistant to treatment relevant to energy intake.
  • The hormonal  levels of testosterone among men with NSCLC associated with such losses deserve further study.
  • Limitation-(1)Differences in type of tumor and lenght of chemotherapy between the men and women in this study may account for some of the differences reported. (2)The high dropout rate illustrates the problems of making serial measurements in such a seriously ill population.
Funding Source:
Reviewer Comments:

Advantages of "Within Subjects " study design

  • useful in predicting long-term  or cumulative  effects which are normally hard to analyze in a case study or cross-sectional study
  • the research progresses over a period of time allowing for for the influences of competing stimuli on the subjects which might increase the study's external validity.

Disadvantages of "Within Subjects" study design

  • May cause problems of internal validity because the study design does not strictly control for confounding variables
  • the strenth of these studies lie in interviewing the same sample size at different times, this advantage diminishes as the sample size decreases.

This study was reportedly the first to proactively asses energy balance in patients with advanced NSCLC having chemothrapy

The author's conclusion seem appropriate for the study reviewed. The study's limitations are identified and discussed.

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) ???
  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? No
  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? 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) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  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? 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? 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? Yes
  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? 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? 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? ???
  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? ???
  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? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? N/A
  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)? ???
  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? ???
  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? N/A
  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? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???