ONC: Radiation Therapy (2007)


Garcia-Peris P, Lozano MA, Velasco C, De L Cuerda, C, Iriondo T, Breton I, Camblor M, Navarro C.  Prospective study of resting energy expenditure changes in head and neck cancer patients treated with chemoradiotherapy measured by indirect calorimetry.  2005, Nutrition 21: 1107-1112 

PubMed ID: 16308133
Study Design:
Time Study
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To evaluate the course of resting energy expenditure (REE) measured by indirect calorimetry and estimated by the Harris-Benedict formula,  in patients who had head and neck cancer and underwent treatment with chemoradiotherapy.
Inclusion Criteria:

Patients who had head and neck cancer (stages iii and iv)

Exclusion Criteria:
None specified.
Description of Study Protocol:

Recruitment :  Not specified


Design : Prospective, time series


Blinding used (if applicable)  N/A


Intervention (if applicable)  N/A


Statistical Analysis

  • Non-parametric tests used due to limited sample size
  • Friedman's test: to evaluate difference in REE measured by Indirect Calorimetry (IC) or calculated by the Harris-Benedict (HB) formula during treatment.
  • Wilcoxon's test: to evaluate differences at each point during treatment between methods.
  • Bland-Altman test:  to evaluate clinical concordance between methods



Data Collection Summary:

Timing of Measurements: 

  • Before treatment
  • Weeks 2, 4, and 6 during chemoradiotherapy
  • End of treatment
  • 2 weeks after the completion of treatment


Dependent Variables

Resting Energy Expenditure (REE)

  •  Indirect Calorimetry (IC):  metabolic monitor Deltatrac. Measurements were perfurmed for 30 min. after an overnight fast, and with patients in a supine position.  REE calculated by Weir's formula.
  • Harris Benedict (HB) formula


  • Weight: platform balance, measured to the nearest 0.2 kg
  • Height:  stadiometer, measured to the nearest 0.1 cm
  • Skinfold thickness (triceps and subscapular):  obtained in triplicate using a Holtain caliper (pressure 10 g/mm2, precise to 0.2mm)
  • Midarm circumference: obtained in triplicate using a metric scale to the nearest 0.2 cm.:  calculated as midarm circumference minus the product of 3.14  and triceps skinfold thickness

Independent Variables:

  • treatment with chemoradiotherapy


Control Variables:   None specified.


Description of Actual Data Sample:


Initial N:   18 (15 male, 3 female)

Attrition (final N):  18

Age: 57 + 10.7 yrs (range: 30-71 y)

Ethnicity: Not specified.

Other relevant demographics: None specified.

Anthropometrics:  Before treatment:

  • Weight (kg)  66.1 + 13.7 (43.9 - 92.2)
  • Body Mass Index (BMI) (kg/m2):  24.7 + 4.4 (16.9 - 31.4)
  • Fat free mass (FFM) (%):  71.9 + 5.8 (62.7 - 86.3)
  • Fat mass (FM) (%):   28.3 + 5.8 (13.7 - 37.3)
  • Impedance (IMP):  515 + 92.5 (333 - 683)
  • Triceps skinfold thickness (PTP) (mm):  13.4 + 5.9 (3 - 22.5)
  • Subscapular skinfold thickness (PSB) (mm):  14.2 + 6 (4 - 28)
  • Midarm muscle circumference (MAMC) (cm):  22.2 + 3.4 (15.1 - 27.1)

Location: Spain


Summary of Results:


  • Patients lost weight during treatment:  BMI decreased from 24.7 + 4.4 kg/m2 to 22.3 + 4.2 kg/m2. (p<0.001).  Weight decreased from 66.1 + 13.7 to 59.8 + 12.8 kg (p<0.001).
  • A decrease in visceral proteins was observed:  PSB decreased from 14.2 + 6 mm to 11.9 + 6mm (p<0.002);  MAMC decreased from 22.2 + 3.4 cm to 21.6 + 2.9 cm. (p=.031)
  • Impedance increased from 515 + 92.5 to 574.5 + 102.1 (p<0.002)
  • Changes in FFM, FM and PTP = n.s.

Resting Energy Expenditure:

  • REE (kcal/24 hr) changed significantly during treatment.  IC: p< 0.05;  HB formula: p<0.001)

                                                                               Kcal/24 hr        

                                                                        Mean + S.D. (range) 

                                                      IC                                       HB                                   P

         Before                   1563 + 343 (1110-2520)         1415 + 216 (1070-1720)        0.035

         2 week                  1437 + 313 (1000-2240)         1381 + 199 (1090-1820)        0.320

         4 week                  1380 + 296 (880-2070)           1359 + 213 (1030-1860)        0.477

         End                       1430 + 282 (900-2170)           1307 + 188 (1000-1740)        0.011

         After                      1480 + 262 (1100-2020)         1307 + 187 (1040-1770)        0.002

  • REE measured by IC appeared as a U-shaped curve, with higher levels before treatment, at the end of treatment and 2 wk after treatment.
  • REE as estimated by the HB formula decreased during the entire study period.
  • HB formula underestimated REE measurements compared with IC.  Differences were statistically significant before treatment, at the end of treatment and 2 wk after treatment (p<.05)
  • Same differences were also observed when REE was expressed as kcal/kg body weight (p<0.05) and of FFM (p<.05).
  • Clinical concordance between methods was unacceptable (shown by Bland-Altman graphic).

Other Findings

 Thyroid hormone levels were normal during the study period.

Author Conclusion:
These results suggest that the HB formula is unsuitable in this particular cohort of patients because REE underestimation effects are important and REE is a frequently used method in clinical practice.  This problem cannot be explained on the basis of a stress factor due to variable stress features during treatment, as has been shown by IC measurements.  IC is a suitable method for measuring REE in patients with head and neck cancer during treatment with chemoradiotherapy.
Funding Source:
University/Hospital: Hospital General University Gregorio Maranon
Reviewer Comments:
Small sample is primary limiting factor of this study.  In spite of the small number of subjects, results are clinically relevant in suggesting that IC is a suitable method for measuring REE in patients with head and neck cancer during treatment with chemoradiotherapy.
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? N/A
  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? N/A
  4.1. Were follow-up methods described and the same for all groups? 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? 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? 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? 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? 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? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) 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? 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? ???
  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)? N/A
  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