ONC: Nutrition Status and Outcomes in Adult Oncology Patients (2013)
Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Impact of nutrition on outcome: A prospective randomized controlled trial in patients with head and neck cancer undergoing radiotherapy. Head and Neck. 2005 Aug; 659-668.
PubMed ID: 15920748The researchers' purpose was to determine if a cause-and-effect relationship exists between nutrition interventions, including dietary counseling or the use of oral nutritional supplements, and function and clinical outcomes in head and neck cancer patients receiving radiotherapy (RT).
- All consecutive, ambulatory patients receiving RT for head and neck cancer at the study center between July 2000 and March 2003 were considered eligible
- No distinction was made between patients who received primary RT, RT adjuvant to surgery, RT combined with chemotherapy or RT received for palliation
- Patient had to be receiving RT of 70 Gy in 35 fractions.
- Renal disease
- Diabetes mellitus.
Recruitment
Not specifically mentioned; all consecutive study center patients who met the inclusion criteria during the study period were considered eligible.
Design
- All patients were referred for pre-operative RT
- All patients had previously received chemotherapy: 5-fluorouracil + cisplatin + folinic acid
- Patients were randomized to one of three groups:
- Group 1: Dietary counseling with regular foods
- Group 2: Usual diet plus supplements
- Group 3: Ad lib intake
- Randomly assigned patients received identical scheduled visits and contact time with the research dietitian
- The goal of nutrition therapy was to help each patient achieve his or her estimated energy and protein requirements
- The dietitian prescribed a therapeutic diet using regular foods
- Diet was modified to meet individual requirements based on:
- Adequate intake
- Alleviation of symptoms
- Psychological factors
- Functional capacity of the GI tract
- Diet was designed to be as close to each patient's usual eating pattern as possible
- The diet prescription identified the type, amount and frequency of feedings
- Goal calorie and protein level was specified
- Restrictions, limitations or increases in dietary intake were specified
- Diet was modified to meet individual requirements based on:
- Patients randomly assigned to the nutrition supplement group received oral nutrition supplements as an adjunct to the patients' regular diet
- Ready to use, high-protein, energy-dense commercial supplements were used
- All supplements were the same brand (brand not mentioned)
- Patients could select their preferred flavors
- Patients received two cans of supplement per day
- Each 200ml can of supplement contained 200kcal per 20g protein
- Supplement consumption records were kept daily by patients and verified by a caretaker
- Patients assigned to the ad lib intake group were instructed to maintain their regular diet
- Study measures were assessed and results were calculated.
Blinding Used
- Patients were stratified by cancer stage prior to randomization:
- Patients were randomized in permutation blocks of three
- Sequential, numbered, opaque sealed envelopes contained computer-generated random assignments
- Study personnel were blinded to the randomization sequence; a copy was kept separate from study personnel
- Randomization envelopes were opened prior to each patient's first appointment by a person blinded to the study procedures.
Intervention
- Individualized nutrition counseling by the study dietitian
- Provision of two oral supplements per day in addition to regular diet; supplements provided a total of 400kcals per 40g protein per day
- Ad lib intake.
Statistical Analysis
- Power calculations were completed for the study:
- Minimum sample size of 40 patients was required to detect, with a significance level of 0.01 and power of 0.85:
- Difference in body weight of 1.9kg
- Difference in nutritional intake of 25%
- Difference in QOL score of 20%
- Power calculations were based on changes observed in a previous pilot study of 36 patients
- Minimum sample size of 40 patients was required to detect, with a significance level of 0.01 and power of 0.85:
- Statistical analysis completed with SPSS 11.5 (SPSS Inc., Chicago, IL), and EPI-Info 2000 (Centers for Disease Control, Atlanta, Georgia)
- All analysis were conducted on an intent-to-treat basis; any missing data was replaced with the average of the study group, which would have no effect on the estimators
- Continuous variables were analyzed using one-way analysis of variance (ANOVA) or Wilcoxen rank sum tests
- Categorical variables, incidence, prevalence and frequency were analyzed with the chi-square test
- Univariate or multiple correlations were analyzed with two-tail non-parametric Spearman tests
- Two-tailed multiple correlation analysis was performed to determine the relationship of dietary intake and RT-induced symptoms on worsening nutritional status
- Statistical significance level was P<0.05.
Timing of Measurements
Data Collection by Days | ||||||||||
Baseline | RT Treatment Period | End RT | Three Months Following End RT | |||||||
Day | 7 | 14 | 21 | 28 | 35 | 42 | 49 | 139 | ||
Measure | x | |||||||||
Demography | x | |||||||||
Medical history | x | |||||||||
Informed consent | x | |||||||||
Randomizations | x | |||||||||
Medications* | x | x | x | x | x | x | x | x | x | |
PG-SGA nutritional status | x | x | x | x | x | x | x | x | x | |
Weight | x | x | x | x | x | x | x | x | x | |
Diet history | x | x | ||||||||
24-hour recall | x | x | x | x | x | x | x | x | ||
RT-induced morbidity | x | x | x | x | x | x | x | x | ||
QOL s/EORTC QLQ-C30 | x | x | x | |||||||
Nutritional intervention (Gp 1, Gp 2) | x | x | x | x | x | x | x | x | ||
Acceptability and compliance | x | x | x | x | x | x | x | x |
*Note: Use of dietary supplements was also monitored.
Dependent Variables
- Variable 1:
- Nutrition outcomes:
- Nutritional intake (energy and protein intake)
- Basal energy requirements estimated using the World Health Organization formula for patients 60 years or less, or the Owen et al formula for patients older than 60 years
- To estimate daily energy requirements (EER), basal requirements were multiplied by a 1.5 activity factor
- Protein requirements were estimated from age and sex standardized reference values, and ranged from 0.8g per kg per day to 1.0g per kg per day
- Burke's diet history, along with multiple and sequential 24-hour recall evaluations (two weekdays and one weekend day), were performed at each
- Nutritional status [measured using Ottery's Patient Generated Subjective Global Assessment (PG-SGA)]
- Validated tool designed for patients with cancer
- Measures three areas:
- Weight changes, symptoms, alterations in food intake and functional capacity
- Components of metabolic stress
- Physical examination
- Patients were classified as normal, moderately malnourished or severely malnourished
- Nutritional intake (energy and protein intake)
- Nutrition outcomes:
- Variable 2: Symtom-induced morbidity
- Measured using the PG-SGA
- Addresses symptoms: Anorexia, nausea, constipation, mucositis, vomiting, diarrhea, xerostomia, pain
- Measured using the PG-SGA
- Variable 3: Quality of life (QOL)
- Assessed with the EORTC Quality of Life questionnaire version 3.0
- Includes six function scales (physical, emotional, cognitive, social, role and global health/QOL
- Includes three symptom scales (fatigue, pain, nausea/vomiting)
- Includes six single items (symptoms, financial impact)
- Assessed with the EORTC Quality of Life questionnaire version 3.0
Independent Variables
-
Dietary counseling
-
Oral nutrition supplements.
Control Variables
-
Presence of head and neck cancer
-
Receiving radiation therapy.
- Initial N: N=75 (60 males, 15 females)
- Group 1 (individualized dietary counseling based on regular foods): N=25
- Group 2 (supplement group): N=25
- Group 3 (control group; ad lib intake): N=25
- Attrition (final N):
- All data was analyzed on an intent-to-treat basis; all enrolled patients accounted for; no patients lost to follow-up
- All patients completed the study
- No patients took any other dietary supplements during the study period
- Age: 60±11 (36 to 79) years
- Other relevant demographics:
- Patients had cancers of the base of the tongue, nasopharynx, oropharynx or larynx
- 30 patients with Stage I/II disease; 45 patients with Stage III/IV disease
- 16 patients in Group 1 were malnourished; 14 patients in Group 2 were malnourished; and 15 patients in Group 3 were malnourished
- 56% of the malnourished patients had Stage III/IV disease; 4% of the malnourished patients had Stage I/II disease
- All patients had received prior chemotherapy with an identical regimen (5-flourouracil + cisplatin + folinic acid)
- All patients were receiving radiotherapy in preparation for surgery
- Anthropometrics: At baseline, there were no significant differences between groups for energy and protein intake, prevalence of malnutrition or presence of symptom-induced morbidity
- Location: Radiotherapy Department, University Hospital of Santa Maria, Lisbon, Portugal.
Nutritional Outcomes
- Energy intake:
- Energy intake at end of RT compared with initiation of RT:
- Group 1: Net increase, +521kcal per day (358 to 732), P=0.002
- Group 2: Net increase, +322kcal per day (286 to 412), P=0.005
- Group 3: Net decrease, -400kcal per day (201 to 502), P<0.01
- Energy intake at three-month follow-up:
- Group 1: Maintained increase in energy intake
- Group 2: Energy intake decreased to either baseline or below baseline, P=0.005
- Group 3: Energy intake decreased to either baseline or below baseline, P=0.005
- Energy intake at end of RT compared with initiation of RT:
- Protein intake:
- Protein intake at end of RT compared with initiation of RT:
- Group 1: Net increase, +26g per day (20 to 34), P=0.006
- Group 2: Net increase, +35g per day (20 to 44), P=0.001
- Group 2 protein intake was higher than Group 1 protein intake, P=0.06
- Group 3: Net decrease, -15g per day (9 to 21), P<0.01
- Protein intake at three-month follow-up:
- Group 1: Maintained increased protein intake
- Group 2: Protein intake decreased to either baseline or below baseline, P<0.05
- Group 3: Protein intake decreased to either baseline or below baseline, P<0.05
- Protein intake at end of RT compared with initiation of RT:
- Nutritional status:
- Group 1: Eight of 16 malnourished patients at initiation of RT improved their nutrition status [net average recovery at three-months follow-up: 4kg (two to six)]
- Group 2: No patient showed improved nutrition status
- Group 3: No patient showed improved nutrition status.
Changes in Nutritional Status during RT and at Three Months
Group 1 | Group 2 | Group 3 | ||||||||||||
Decline | Maintaind/Improved | Decline | Maintained/Improved | Decline | Maintained/Improvedd | |||||||||
Method | End RT | Three Months | End RT | Three Months | End RT | Three Months | End RT | Three Months | End RT | Three Months | End RT | Three Months | P1* | P2* |
PG-SGA | 5 | 3 | 20 | 22 | 19 | 24 | 6 | 1 | 24 | 25 | 1 | 0 | <0.002 | <0.001 |
*P1 describes the significance of the statistical difference between the intervention groups regarding nutritional decline, at the end of RT and at three months follow-up.
*P2 describes the significance of the statistical difference between the intervention groups regarding maintenance or improvement of nutritional status, at the end of RT and at three months' follow-up.
Symptom-induced Morbidity Outcomes
- By end of RT, 90% of the study participants experienced radiation-induced toxicity
- The incidence did not differ significantly between groups (P<0.08)
- A trend for reduced symptoms was found in Group 1 vs. Groups 2 and 3 (P<0.07)
- At three-month follow-up, a significant difference in Grade 1 and 2 anorexia, nausea/vomiting, xerostomia and dysgeusia was found between Group 1 patients (90% showed improvement), Group 2 patients (67% showed improvement) and Group 3 patients (51% showed improvement); P<0.0001. Reduction of Grade 1 + 2 dysphagia/odynophagia was not significant between groups.
- During RT, medications (oral antifungal solutions, local anesthetics and anti-inflammatories) were prescribed as appropriate for symptom control in 57% of Group 1 patients, 61% of Group 2 patients and 68% of Group 3 patients; however, the difference was not significant
- Dietary intake was correlated significantly with nutritional status in all groups (R≤-0.59, P≤0.002).
RT-induced Morbidity According to Severity Grade
Group 1 | Group 2 | Group 3 | |||||||||||||
Grade 1 | Grade 2 | Grade 1 | Grade 2 | Grade 1 | Grade 2 | ||||||||||
Symptoms | End RT | Three Months | End RT | Three Months | End RT | Three Months | End RT | Three Months | End RT | Three Months | End RT | Three Months | P1* | P2* | P3* |
Anorexia | 10 | 1 | 2 | 0 | 9 | 4 | 5 | 3 | 9 | 5 | 7 | 3 | <0.05 | <0.12 | <0.001 |
Nausea/Vomiting | 4 | 0 | 1 | 0 | 3 | 2 | 2 | 1 | 3 | 2 | 2 | 1 | <0.001 | <0.10 | <0.05 |
Xerostomia |
12 | 2 | 3 | 0 | 10 | 6 | 6 | 3 | 10 | 5 | 7 | 3 | <0.04 | <0.05 | <0.0003 |
Dysgueusia |
10 | 1 | 7 | 2 | 10 | 6 | 11 | 5 | 11 | 5 | 12 | 6 | <0.04 | <0.008 | <0.0004 |
Odynophagia/dysphagia |
14 | 2 | 8 | 1 | 12 | 3 | 10 | 3 | 12 | 6 | 12 | 6 | <0.0001 | <0.05 | <0.0002 |
*P1 describes the significance of the statistical difference between the intervention groups regarding the reduction of Grade 1 symptoms, at the end of RT and at three months' follow-up.
*P2 describes the significance of the statistical difference between the intervention groups regarding the reduction of Grade 2 symptoms, at the end of RT and at three months' follow-up.
*P3 describes the significance of the statistical difference between the intervention groups regarding the reduction of Grade 1 + 2 symptoms, at the end of RT and at three months' follow-up.
Quality of Life Outcomes
- At end of RT:
-
For Group 1, all QOL scores significantly improved (P<0.003)
- QOL scores were correlated with increases in energy and protein intake (R<0.83; P<0.001)
- QOL scores were related to improvement in nutritional status (P<0.05)
- For Group 2, all function scores improved (P<0.009); function scores were correlated with improvement in protein intake (R<0.58; P<0.05)
- For Group 3, all QOL scores worsened as nutritional intake and nutritional status worsened (P<0.0001, P<0.002, respectively)
-
- At three-month follow-up:
- For Group 1, all patients maintained or improved overall QOL
- QOL was positively correlated with maintenance or improvement of nutritional status (P<0.008) and adequate energy and protein intake (P<0.01)
- Function scores were improved or maintained
- Symptom scales were significantly improved over baseline (P<0.002)
- For Group 2, patients either maintained or experienced a decline in QOL (P<0.03). Decline in QOL was associated with poor dietary intake (P<0.003) and worsened nutritional status (P<0.002)
- For Group 3, function scores deteriorated further when compared with baseline and end of RT
- Decline in function scores was associated with inadequate energy and protein intake (P<0.001) and worsened nutritional status (P<0.002)
- Symptom scores were worse than at baseline (P<0.003). The worst symptom scores were associated with poor energy and protein intake (P<0.005).
- For Group 1, all patients maintained or improved overall QOL
- Nutrition is a key determinant of quality of life in patients with cancer
- Both at end of RT and at three months' follow-up, dietary counseling resulted in significantly improved QOL function scores, in conjunction with sufficient intake and adequate nutritional status
- Patients in Group 2 showed an improvement in QOL function scores as long as supplementation continued, but when supplementation was discontinued, QOL scores declined
- Patients in Group 3, who received no nutrition counseling or supplementation, showed a significant decrease in QOL function scores throughout the entire study period
- The benefits of dietary counseling for QOL scores included improved physiological and clinical outcomes
- Nutrition intervention, including nutrition assessment, dietary counseling, diet education, monitoring compliance and symptom management, was central to the improvement of patients' outcomes, both nutritional and non-nutritional
- Both dietary counseling and oral supplementation improved patient outcomes in the short term, with dietary counseling showing an equal or greater benefit than supplementation; however, at the three-month follow-up, only dietary counseling resulted in improved patient outcomes
- The authors urge early nutrition intervention in this patient population.
University/Hospital: | Instituto de Medicina Molecular Faculdade de Medicina da Universidadede Lisboa (Portugal), Santa Maria University Hospital (Portuagal) |
- Well-designed RTC; included power calculation, randomization with blinding of investigator assigning patients to groups; used validated instruments to measure outcomes; used concurrent controls
- Patients receiving RT combined with chemotherapy and RT combined with surgery were included in the study
- Records of supplement consumption were kept by patients and patient caregivers
- Basal energy requirements, EER and protein requirements were calculated from formulas and reference values; 1.5 activity factor was used for all patients
- Many more men than women in study; no information provided for number of males and females in each study group.
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) | 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? | 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? | 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? | 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? | 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.) | Yes | |
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? | 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? | 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? | 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)? | Yes | |
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? | 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? | 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 | |