ONC: Radiation Therapy (2007)
NEUTRAL:For inclusion in this study, individuals must:
- Be ambulatory
- Have a diagnosis of head and neck cancer (oral cavity, oropharynx, supraglottis, larynx, hypopharynx, nasopharynx, parotid, unknown primary)
- Planned to receive a potentially curative, five to eight week course of radiation therapy
Individuals excluded if:
- Planned to receive both chemotherapy and radiation therapy.
Recruitment:
- 50 consecutive head and neck cancer patients being treated at Fox Chase Cancer Center, Philadelphia, PA, who met study criteria
Design:
- Randomized controlled trial
- Patients randomly assigned to liquid nutritional supplement (Sustacal™ (Mead Johnson) - 960 or 1080 Kcal/day) plus usual diet or no supplement (usual diet only)
- All patients were seen on a weekly basis
- All patients received intensive nutritional counseling
- Nutrition counseling included recommendations for pureed, liquid, or soft diets when appropriate
- Recommended diets consisted of common household foods
Blinding used (if applicable):
- Not applicable
Intervention (if applicable):
Patients randomly assigned to receive:
- Liquid nutritional supplement (Sustacal™ (Mead Johnson) - 960 or 1080 Kcal/day) plus usual diet
- Usual diet - no supplement
Statistical Analysis
- Mann-Whitney U test
- t-test
- A Mahalinobis score was used to determine if suppelementation added to patients' nutrient content, or if supplements substituted for nutrients which would otherwise have been eaten
- The Mahalinobis score was determined by:
- Constructing a linear regression over weeks 3, 5, 7, and 10 for each individual, for each of the following variables: total kcals, residual kcals (total kcals - supplementary kcals), total protein, residual protein (total protein - supplementary protein)
- Each regression line provided a score for "a" and "b", as in y = a + bx, for each individual
- Points were plotted; the resulting scatter plots for the supplement group and the nonsupplement group were compared
- The Mahalinobis score was determined by:
Timing of Measurements
- Pre-treatment and at 3, 5, 7, and 10-weeks
- 6 months post-treatment
- Nutritional assessment was performed at pre-treatment, 3, 5, 7, and 10 weeks, and at 6 months
- Body weight, serum albumin, serum transferrin, and 24-hour recalls were measured at these intervals
- Since the principle investigator was a registered dietitian, this analyst is assuming that nutrition assessment was performed by registered dietitians
- Calorie and protein intake were evaluated at weeks 3, 5, 7, and 10 to determine the effect of oral supplements on total dietary intake
- Statistical calculations were based on residual calories (total calories - supplementary calories) and residual protein (total protein - supplementary protein)
- Radiation side effects were evaluated by a radiation oncologist on a weekly basis
- Treatment side effects were noted
- Interruptions of treatment were noted
- Tumor status was evaluated 3 to 4 months post treatment
Dependent Variables
- Body weight: lbs
- Serum albumin: gm/dL
- Serum transferrin: mg/dL
- Dietary intake: 24 hour dietary recall
- Total kcals vs residual kcals
- To determine whether oral supplements added to nutrient content of diet or displaced nutrients
Independent Variables
- Liqiud nutritional supplement vs. no supplement
Control Variables
- Pretreatment weight
- Pretreatment protein status (albumin and transferrin)
- Disease site
- Disease stage
Initial N:
N = 50 (29 males, 21 females)
- Nutrition supplement group: n = 23 (9 male, 14 female)
- Tumor stage: I = 5; II = 7; III = 3; IV = 8
- Pretreatment chewing difficulty: n = 6
- Pretreatment swallowing difficulty: n = 9
- No nutrition supplement group: n = 27 (20 male, 7 female)
- Tumor stage: I = 4; II = 9; III = 10; IV = 4
- Pretreatment chewing difficulty: n = 8
- Pretreatment swallowing difficulty: n = 9
Attrition (final N): Not specified; Table of tumor status at 3 months accounts for all 50 patients with 47 surviving and 3 deaths.
Age: Intervention Group: Median = 64.1 years; Range = 34-88 years. Control Group: Median = 68.3 years; Range = 43-80 years.
Ethnicity: Not specified.
Other relevant demographics: Not discussed.
Anthropometrics:
- There were no significant differences between groups in weight loss between usual weight and pretreatment weight
- Mean pretreatment weight was not significantly different
- There were no significant differences between groups in pretreatment serum albumin and pretreatment serum transferrin
- No assessment of variable distribution or presence/absence of statistically significant differences was provided for age, sex, radiation dose, pretreatment chewing difficulty, and pretreatment swallowing difficulty
Location: Department of Surgery, Fox Chase Cancer Center, Philadelphia PA and Department of Radiation Medicine, Abington Memorial Hospital, Abington, PA.
BASELINE
|
Variables |
Treatment Group |
Control group |
Statistical Significance of Group Difference |
|
Body weight (lbs) |
150.9 + 36.6 |
151.9 + 36 |
NS |
| Albumin (gm/dL) |
4.11 (no CI provided) |
4.08 (no CI provided) |
NS |
| Transferrin (mg/dL) |
258 ( no CI provided) |
261 (no CI provided) |
NS |
| Dietary Intake (Kcal per 24 hour recall) |
N/A |
N/A |
NS |
| Dietary Intake (g protein per 24 hour recall) |
N/A |
N/A |
N/A |
WEEK 3
|
Variables |
Treatment Group |
Control group |
Statistical Significance of Group Difference |
|
Body weight (%)1 |
100% of baseline wt |
99% of baseline wt |
NS |
| Albumin (gm/dL)2 |
4.06 |
4.04 |
N/A |
| Transferrin (mg/dL)3 |
258 |
261 |
N/A |
| Dietary Intake (Kcal per 24 hour recall)4 |
1929.8 + 605.3 |
1624.3 + 528.7 |
p = 0.035 |
| Dietary Intake (g protein per 24 hour recall)4 |
88.4 + 31.9 |
66.9 + 26.1 |
p = 0.005 |
WEEK 5
|
Variables |
Treatment Group |
Control group |
Statistical Significance of Group Difference |
|
Body weight (%)1 |
98% of baseline wt |
97% of baseline wt |
NS |
| Albumin (gm/dL)2 |
3.89 |
4.03 |
N/A |
| Transferrin (mg/dL)3 |
239 |
259 |
N/A |
| Dietary Intake (Kcal per 24 hour recall)4 |
1929.8 + 605.3 |
1624.3 + 528.7 |
p = 0.048 |
| Dietary Intake (g protein per 24 hour recall)4 |
88.4 + 31.9 |
66.9 + 26.1 |
p = 0.005 |
WEEK 7
|
Variables |
Treatment Group |
Control group |
Statistical Significance of Group Difference |
|
Body weight (%)1 |
97% of baseline wt |
96% of baseline wt |
NS |
| Albumin (gm/dL)2 |
4.05 |
4.05 |
NS |
| Transferrin (mg/dL)3 |
250 |
264 |
N/A |
| Dietary Intake (Kcal per 24 hour recall)4 |
1929.8 + 605.3 |
1624.3 + 528.7 |
p = 0.048 |
| Dietary Intake (g protein per 24 hour recall)4 |
88.4 + 31.9 |
66.9 + 26.1 |
p = 0.005 |
WEEK 10
|
Variables |
Treatment Group |
Control group |
Statistical Significance of Group Difference |
|
Body weight (%)1 |
94% of baseline wt |
95% of baseline wt |
NS |
| Albumin (gm/dL)2 |
4.11 |
3.95 |
N/A |
| Transferrin (mg/dL)3 |
255 |
249 |
N/A |
| Dietary Intake (Kcal per 24 hour recall)4 |
1929.8 + 605.3 |
1624.3 + 528.7 |
p = 0.048 |
| Dietary Intake (g protein per 24 hour recall)4 |
88.4 + 31.9 |
66.9 + 26.1 |
p = 0.005 |
6 MONTHS
|
Variables |
Treatment Group |
Control group |
Statistical Significance of Group Difference |
|
Body weight (%)1 |
89.5% of baseline wt |
91% of baseline wt |
NS |
| Albumin (gm/dL)2 |
4.08 |
3.88 |
N/A |
| Transferrin (mg/dL)3 |
253 |
242 |
N/A |
| Dietary Intake (Kcal per 24 hour recall)4 |
N/A |
N/A |
N/A |
| Dietary Intake (g protein per 24 hour recall)4 |
88.4 + 31.9 |
66.9 + 26.1 |
p = 0.005 |
Mean energy intake, protein intake, and residual kcals and protein during weeks 3, 5, 7, and 10:
|
Variables |
Treatment Group |
Control group |
Statistical Significance of Group Difference (one-tailed) |
| Total kcals |
1929.8 + 605.3 |
1624 + 528.7 |
0.035 |
| Residual kcals |
1392.4 + 593.5 |
1604.3 + 511.4 |
0.048 |
| Total protein (gms) |
88.4 + 31.9 |
66.9 + 26.1 |
0.005 |
| Residual protein (gms) |
55.4 + 27.1 |
65.7 + 25.0 |
0.035 |
1 Data provided graphically. Difficult to determine absolute weight change in lbs; not possible to determine mean weight of each group at each time point; not possible to determine confidence intervals, but visual inspection indicates confidence interval overlap (no significant differences between groups).
2 Data provided graphically. Not possible to determine confidence intervals. Not possible to determine if there are significant differences between groups.
3 Data provided graphically. Not possible to determine confidence intervals. Not possible to determine if there are significant differences between groups.
4 Data on dietary intake presented for each group as combined average for weeks 3, 5, 7, and 10. Data on dietary intake for individual time points not available.
Other Findings:
Total mean energy intake/day for supplemented patients was about 300 kcals greater than nonsupplemented patients
Nutritional supplements appear to add to the diet rather than displace kcal and protein. Some displacement of food intake occurs, but the overall effect is a significant increase in intake of kcal and protein with supplement use.
- Oral supplements in conjunction with nutritional counseling maintained serum albumin levels in well nourished head and neck cancer patients compared to control group
- Enteral support is most effect in preserving visceral protein levels if initiated before decline in nutritional status is evident.
- All patients in the head and neck cancer patient population should be considered candidates for nutritional intervention
- Supplementation increased rather than displaced macronutrient content of usual diet
- Weight loss occurred despite oral supplementation both during and after treatment
- Oral supplementation did not affect survival status, tumor response, treatment side effects, or treatment interruptions
- Further trials with a clear liquid (not milky), non-acidic supplement of comparable nutrient density would be suitable for a trial in this population
| Industry: |
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| University/Hospital: | Fox Chase Cancer Center Central, Abington Memorial Hospital | ||
| In-Kind support reported by Industry: | Yes |
- Older study; may not adhere to current standards for methodological rigor
- Older study; nutrition supplements/radiation therapy methods may be different from current practices
- Data presentation is a mix of text and graphical making comparisons between the intervention and control groups difficult in some cases
- Noted the large difference in male/female subjects between treatment groups
- 11 vs 14 stage III and IV tumors in the nutrition supplement and no nutrition supplement groups, respectively
- Authors noted that no patient in the nutrition supplement group consumed the entire prescribed amount of supplement; only 7 patients took at least 80%
- Authors noted that one patient in the non-supplemented group took a supplement for the first 10 weeks
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Quality Criteria Checklist: Primary Research
|
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| 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) | 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? | No | |
| 1.3. | Were the target population and setting specified? | ??? | |
| 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? | No | |
| 2.4. | Were the subjects/patients a representative sample of the relevant population? | ??? | |
| 3. | Were study groups comparable? | ??? | |
| 3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | ??? | |
| 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? | No | |
| 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%.) | ??? | |
| 4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
| 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? | ??? | |
| 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.) | ??? | |
| 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? | 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? | No | |
| 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? | ??? | |
| 7.6. | Were other factors accounted for (measured) that could affect outcomes? | No | |
| 7.7. | Were the measurements conducted consistently across groups? | ??? | |
| 8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | ??? | |
| 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? | ??? | |
| 8.3. | Were statistics reported with levels of significance and/or confidence intervals? | No | |
| 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)? | ??? | |
| 8.6. | Was clinical significance as well as statistical significance reported? | No | |
| 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? | No | |
| 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 | |