The inclusion criteria were:
- Patients referred for radiotherapy.
- All patients who gave written consent to participate in the study.
- Patients with renal disease and/or diabetes mellitus.
Recruitment - Between the periods of July 2000 and March 2003, all consecutive CRC ambulatory patients referred for RT were considered eligible, regardless of whether the proposed RT was primary, adjuvant to surgery, combined with chemotherapy, or with palliative intent.
Design : Prospective, randomized, controlled trial. Patients stratified by cancer stage were randomly assigned at enrollment in permutation blocks of three, using a sequential series of numbered opaque sealed envelopes containing computer generated random assignments.
Blinding used: - A copy of the randomized sequence was kept separately from the study personnel. Randomization envelopes were opened before the first appointment with the patients by a person blind to the study procedures.
Intervention:
After randomization, patients were assigned to one of three groups:
- Group I (G1;N=37) received individualized dietary counseling based on regular foods.The diet prescription identified the type, amount, and frequency of feeding; specified the calorie and protein level to attain; and included any restrictions and limited or increased individual dietary components.
- Group 2 (G2;n=37) were asked to consume 2 cans per day of high protein liquid supplement in addition to their usual diet. Supplements used throughout the study were always the same commercial brand. Each 200-ml can provided 20g protein and 200 kcal. Compliance was monitored by using a supplement consumption record, which was kept daily by patients and verified by a caregiver or relative.
- Group 3 (G3; n=37), the control group, were asked to maintain their ad libitum intake.
- Randomly assigned patients had scheduled visits and identical contact time with the research dietitian.
Statistical Analysis was performed using SPSS 11.5(SPSS,Inc,Chicago,Il) and EPI-Info 2000(Centers for Disease Control, Atlanta, GA)
- All analyses were conducted on an intention-to-treat-basis, and therefore available data from all study patients were used. If any missing data were observed,the missing value(s)would be replaced by the avaerage of the study group,which would have no effect on the estimators. Study groups had been assessed for comparability at time of entry into the study.
- Data related to incidence, prevalence, or frequency (symptoms,cancer stages,and nutritional status categories ) were expressed as number and/ or percentages.
- Data related to age was expressed as mean ± standard deviation and range.
- Data related to energy and protein intake were expressed as the median and range.
- The Quality of Life scores were expressed as median values.
- The continous variables were analyzed using the on-way analyses of variance or Wilcoxon rank sum test as appropriate.
- The categorical variables and incidence,prevalence ,or frequency were evaluated by the chi-square test.
- Univariate or multiple correlations were`assessed by two-tailed nonparametric Spearman's tests.
- Statistical significance was set for a P value less than .05.
A miniumum sample size of 58 patients was calculated to detect a difference in body weight of 1.9 kg,in nutritional intake 25%, and in QoL scores of 20%(ie, an effect size of 0.9) with a significance level of .01 between groups and a power of 0.85.
Statistical power was based on on the changes observed in weight, nutritional intake, and QoL from a pilot study conducted in 46 patients with CRC.
Timing of Measurements - The nutritional intake (diet history), nutritional status (Ottery's Subjective Global Assessment), and QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaireversion 3.0) were evaluated at:
- Baseline
- At the end of radiotherapy
- 3 months after radiotherapy
All patients were referred for preoperative RT combined chemotherapy comprising fluorouracil plus folonic acid-based regimens administered concurrently with the first and the last days of RT.
Dependent Variables
- Nutrition intake: nutritional requrements and dietary assessment.
- The basal energy requirements were measured using the World Health Organization for patients <= 60 years of age or by the Owen et al formula for patients aged older than 60 years
- Basal energy requirements were multiplied by a 1.5 activity factor.
- Daily protein requirements were estimated by comparison with age and sex standardized reference values,which range between 0.8 and 1.0 g/kg per day.
- Nutritional intake was derived from a 24 -hour -recall questionnaire . The primary source of the dietary data was Burke's diet history,which was further complemented by multiple and sequential 24-hour-recall evaluations (2 weekdays and 1 weekend day) undertaken at every scheduled visit.
- Both energy and protein intakes were always analyzed together. The software DIETPLAN version 5 Windows (2003:Forestfield Software Ltd,Horsham,United Kingdom) was used to analyzed nutrient contents of regular foods and meals.
2. Nutritional status - Nutritional assessment was performed using two methods.
- 1st method: Ottery's Patient Generated Subjective Global Assessment (PG-SGA) is a validated nutrition assessment tool for cancer patients that addresses weight changes,symptoms(anorexia, nausea, constipation, mucositis, vomiting, diarrhea, xerostomia, pain), alteration in food intake by comparing with the usual intake and functional capacity; components of metabolic stress, including sepsis, neutropenic or tumor fever, and use of corticosteroids; and physical examination, including subcutaneous fat (triceps skinfold and at the level of lower ribs in the mid/axillary line), muscle bulk and tone in the temporal, deltoids, and quadriceps areas, and ankle or sacral edema or ascites.
- Nutritional status was categorized in three degrees: normal, moderate, and severe malnutrition
- 2nd method: Used anthropometric data: height was measured in the standing position using a stadiometer and weight was determined with a Jofre floor scale. Body mass index (BMI)was then calculated according to the formula weight(kg)/height(m)2, classified as malnutrition if less than 20 kg/m2 or normal if >= 20 kg/m2
3. Quality of Life
- QoL was assessed using the EORTC Quality of Life Questionnaire (Version 3.0.). This instrument is a 30 item cancer specific questionnaire including six function scales(physical, emotional, cognitive, social, role,and global health or QoL), three symptom scales(fatigue, pain, nausea or vomiting), and 6 single items assessing symptoms and the financial impact of the disease.
-
Higher scores on the function scales indicate better functioning,whereas higher scores on the symptom scale and single item denote increased symptomatology or worse financial impairment.
-
Original scores were linearly transformed to obtain quantified scores within the range of 0 to 100; in addition, and for better validation in the clinical context,overall scores derived from function scales,symptom scales,and single items were claculated on the basis of the high statistical significance of the interscale correlations,which were calculated according to EORTC guidelines.
Independent Variables
- Recent medications and chemotherapy-throughout RT, all medications and concurrent chemotherapy were registered, and acute RT-induced morbidity was scored from 0 to 4 according to the European Organisation for Research and Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group criteria, in which higher scores indicated increased symptom severity.
- Duration of disease
- Cancer location
- Presence of distant metastases
- Tumor burden according to TNM stage of disease determined by a local and whole-body imaging methods.
- Duration of disease, confirmed by histology, was defined as the length of time (in months) between symptomatic manifestations and study entry.
Control Variables:
1. Dietary Counseling
2. Supplements
3. Control Group
Data collected at baseline and throughout study:
- Demography
- Medical history
- Informed consent
- Randomization
- Concomitant medications
- Nutritional status with PG-SGA
- Weight
- Diet history
- 24-hr recallRT-induced morbidity with EORTC/RTOG
- QoL with EORTC QLQ-C30
- Nutritional interventions(groups 1 and 2)
- Acceptability and compliance.
Initial N: This study included 111 free living patients (66 males ,45 females)
- Group I: (dietary counseling, regular foods) n = 37
- Group II: (protein supplements) n = 37
- Group III: (ad libitum intake) n = 37
Attrition (final N):
Age: 58±15 years(range ,32-88 years)
Ethnicity: Not specified
Other relevant demographics: TNM Stage- 45 patients were stage I/II; 66 were in stage III/IV
Anthropometrics :N/A
Location: Santa Maria University Hospital, Lisbon,Portugal.
Table 1. Data Collection,Nutritional Intervention, and Visit Schedule
Visit
|
Table 2: Changes in Nutritional Status During RT at 3 Months Categorized According to PG-SGA and BMI
Group 1: Individual Diet Counseling
Decline | Decline |
Maintained/or improved |
Maintained/or mproved |
|||
Methods | End RT | 3 mos. |
End RT |
3 mos. |
p* |
p** |
PG-SGA |
3 |
10 |
34 |
27 |
<.002 | <.001 |
BMI |
1 |
2 |
36 |
35 |
NS | NS |
NOTE: Data are expressed as number of patients. Abbreviations :RT,radiation therapy;PG-SGA,Ottery's Patient Generated Subjective Global Assessment;BMI,body mass index;NS,not significant. *Expresses the significance of statistical differences between intervention groups,regarding nutritional decline both at the end of RT and at 3 mos. ** Expresses the significance of statistical differences between intervention groups,regarding maintenance or improvement of nutritional status at the end of RT and at 3 months. |
Table 2(continued)
Group 2: High Protein Liquid Supplement
Maintained or/improved Maintained or/Improved End RT 3 mos. 19 24 18 13 3 6 34 31
Decline
Decline
Methods
End RT
3 mos.
p*
p**
PG-SGA
<.002
<.001
BMI
NS
NS
NOTE: Data are expressed as number of patients. Abbreviations :RT,radiation therapy;PG-SGA,Ottery's Patient Generated Subjective Global Assessment;BMI,body mass index;NS,not significant. *Expresses the significance of statistical differences between intervention groups,regarding nutritional decline both at the end of RT and at 3 mos. ** Expresses the significance of statistical differences between intervention groups,regarding maintenance or improvement of nutritional status at the end of RT and at 3 months. |
Table 2(continued)
Group 3: Ad Libitum Food Intake
Decline | Decline |
Maintained or/improved |
Maintained or/Improved |
|||
Methods | End RT | 3 mos. |
End RT |
3 mos. |
p* | p** |
PG-SGA |
34 |
36 |
3 |
1 |
<.002 |
<.001 |
BMI |
5 |
8 |
32 |
29 |
NS |
NS |
NOTE: Data are expressed as number of patients. Abbreviations :RT,radiation therapy;PG-SGA,Ottery's Patient Generated Subjective Global Assessment;BMI,body mass index;NS,not significant. *Expresses the significance of statistical differences between intervention groups,regarding nutritional decline both at the end of RT and at 3 mos. ** Expresses the significance of statistical differences between intervention groups,regarding maintenance or improvement of nutritional status at the end of RT and at 3 months. |
Table 3: RT-Induced Morbidity Categorized According to Severity Grade
Group1: Individual Diet Counseling
Grade 1 | Grade 1 | Grade 2 | Grade 2 | ||||
Symptoms | End RT | 3 mos. | End RT | 3 mos | p* | p** | p*** |
Anorexia |
20 |
6 |
13 |
1 |
<.02 | <.01 | <.001 |
Nausea or vomiting |
27 |
0 |
7 |
0 |
<.001 | .17 | <.0001 |
Diarrhea |
32 |
0 |
2 |
0 |
<.001 | <.05 | ,.0001 |
Note: Data are expressed as number ;grades 3 and 4 were never observed. Abbreviatios:RT,radiation therapy. * *Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 1 symptom incidence between the end of RT and 3 mos. ** Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 2 symptom incidence between the end of RT and 3 mos. ***Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 1+2 symptom incidence between the end of RT and 3 mos. |
Table 3(continued)
Group 2: High Protein Liquid Supplement
Grade 1 | Grade 1 | Grade 2 | Grade 2 | ||||
Symptoms | End RT | 3 mos. | End RT | 3 mos. | p* | p** | p*** |
Anorexia | 19 | 5 | 14 | 13 | <.02 | <.01 | <.001 |
Nausea or vomiting |
23 | 7 | 10 | 3 | <.001 | .17 | <.0001 |
Diarrhea | 25 | 9 | 9 | 3 | <.001 | <.05 | <.0001 |
Note: Data are expressed as number ;grades 3 and 4 were never observed. Abbreviatios:RT,radiation therapy. * Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 1 symptom incidence between the end of RT and 3 mos. ** Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 2 symptom incidence between the end of RT and 3 mos. ***Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 1+2 symptom incidence between the end of RT and 3 mos. |
Table 3 (continued)
Group 3: Ad Libitum Food Intake
Grade 1 | Grade 1 | Grade 2 | Grade 2 | ||||
Symptoms | End RT | 3 mos. | End RT | 3 mos. | p* | p** | p*** |
Anorexia | 17 | 12 | 17 | 10 | <.02 | <.01 | <.001 |
Nausea or vomiting |
18 | 9 | 16 | 6 | <.001 | .17 | <.001 |
Diarrhea | 18 | 15 | 17 | 13 | <.001 | <.05 | <.0001 |
Note: Data are expressed as number ;grades 3 and 4 were never observed. Abbreviatios:RT,radiation therapy. * Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 1 symptom incidence between the end of RT and 3 mos. ** Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 2 symptom incidence between the end of RT and 3 mos. ***Expresses the significance of statistical differences between intervention groups,regarding the reduction of grade 1+2 symptom incidence between the end of RT and 3 mos. |
Table 4: Median QoL Dimensions Scores
Group 1 : Individual Diet Counseling
Item | onset | End |
3 months |
|
Functional scales |
|
|||
Global QoL |
48 |
75*___ |
82¶€______ |
|
Physical Function |
49 |
74*___ |
79¶______ |
|
Role Function |
50 |
78*___ |
80¶______ |
|
Emotional Function |
55 |
79*___ |
83¶______ |
|
Social Function |
52 |
82*___ |
85¶_______ |
|
Cognitive Function |
64 |
73*___ |
70¶_______ |
|
Symptom,scales | ||||
Fatigue |
30 |
55*– - - |
26€______ |
|
Pain |
25 |
33*- - - |
15¶€______ |
|
Nausea/vomiting |
15 |
50*- - - |
10€______ |
|
Symptom,single items | ||||
Dyspnea |
5 |
8 |
8 |
|
Sleep disturbance |
30 |
40*--- |
29€ |
|
Appetite |
45 |
57*--- |
48€ |
|
Constipation |
12 |
10 |
10 |
|
Diarrhea |
38 |
45... |
39... |
|
Finance |
14 |
14 |
14 |
NOTE: Higher scores on function scales indicate better functioning; higher scores on symptom scales or single item denote increased symptomatology or worse financial impairment. (_____) Highest overall significant improvement; (---)highlights overall significant deterioration; (...) highlights overall nonsignificant deterioration. Abbreviations:QoL,quality of life: RT,radiation therapy. * Significant differences between baseline end of RT. ¶ Significant differences between baseline and at 3 months € Significant differences between end of RT and at 3 months. |
Table 4(cont)
Group 2: High Protein Supplement Intake
Item | onset | End |
3 months |
|
Functional scales | ||||
Global QoL | 46 | 70*____ | 62€ _____ | |
Physical Function | 48 | 65*_____ | 60€ ______ | |
Role Function | 52 | 65* _____ | 58 | |
Emotional Function | 50 | 48 | 50 | |
Social Function | 51 | 48 | 51 | |
Cognitive Function | 62 | 62 | 54 | |
Symptom,scales | ||||
Fatigue | 31 | 75*--- | 78¶____ | |
Pain | 22 | 74*--- | 30¶€____ | |
Nausea/vomiting | 14 | 71*--- | 37¶€____ | |
Symptom,single items | ||||
Dyspena | 6 | 6 | 13 | |
Sleep disturbance | 28 | 28 | 75¶€--- | |
Appetite | 40 | 40 | 72¶€--- | |
Constipation | 11 | 9 | 8 | |
Diarrhea | 35 | 81*--- | 72¶€--- | |
Finance | 11 | 11 | 11 |
NOTE: Higher scores on function scales indicate better functioning; higher scores on symptom scales or single item denote increased symptomatology or worse financial impairment. (_____) Highest overall significant improvement; (---)highlights overall significant deterioration; (...) highlights overall nonsignificant deterioration.
Abbreviations:QoL,quality of life: RT,radiation therapy. * Significant differences between baseline end of RT. ¶ Significant differences between baseline and at 3 months € Significant differences between end of RT and at 3 months.
|
Table 4(cont)
Group 3: Ad Libitum Food Intake
Item | onset | End |
3 months |
|
Functional scales | ||||
Global QoL | 47 | 35*--- | 30¶--- | |
Physical Function | 45 | 25*--- | 22¶--- | |
Role Function | 48 | 20*--- | 19¶--- | |
Emotional Function | 51 | 38*--- | 28¶€--- | |
Social Function | 49 | 30*--- | 26¶--- | |
Cognitive Function | 62 | 55*--- | 46¶€--- | |
Symptom,scales | ||||
Fatigue | 29 | 78*--- | 79¶--- | |
Pain | 23 | 78*--- | 73¶--- | |
Nausea/vomiting | 12 | 72*--- | 68¶--- | |
Symptom,single items | ||||
Dyspena | 5 | 6 | 15 | |
Sleep disturbance | 32 | 60*--- | 78¶€--- | |
Appetite | 42 | 65*--- | 75¶€--- | |
Constipation | 9 | 8 | 8 | |
Diarrhea | 33 | 92--- | 78¶€--- | |
Finance | 12 | 12 | 12 |
NOTE: Higher scores on function scales indicate better functioning; higher scores on symptom scales or single item denote increased symptomatology or worse financial impairment. (_____) Highest overall significant improvement; (---)highlights overall significant deterioration; (...) highlights overall nonsignificant deterioration.
Abbreviations:QoL,quality of life: RT,radiation therapy. * Significant differences between baseline end of RT. ¶ Significant differences between baseline and at 3 months € Significant differences between end of RT and at 3 months.
|
Other findings:
- Patients' median baseline estimated requirements and median nutritional intake were similar in all groups
- Energy intake tended to be higher than estimated requirements(P=.07).
- Protein intake was lower than reference values(P=.06)
- This prospective randomized control trial is the first to demonstrate that concurrent individualized dietary counseling, based on regular foods, is the most effective means of improving patients' nutritional intake, status and Quality of Life, thereby lessing radiation therapy-induced morbidity.
- The patients who received oral supplements, only 3 of 6 function scores improved during supplementation, and these were proportional to the increase in dietary intake; however, once the supplementation was discontinued, most functional scores deteriorated.
- Patients not submitted to any nutritional intervention experienced, throughout the entire study, a significant deterioration in function scores and fatigue in direct relationship to the worsening of their nutritional intake and nutritional status.
The authors did note that the Quality of Life tool was a subjective multidimensional construct.
University/Hospital: | University of Lisbon, Santa Maria University Hospital (Portugal) | |
Not-for-profit |
|