EAL

ONC: Radiation Therapy (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the nutritional status of patients with nasopharynx cancer before and after radiotherapy and to examine the relationship among factors affecting nutritional status specifically body weight, body composition, basal metabolic rate, calorie intake and total energy expenditure.

Inclusion Criteria:

Seen at the oncology clinic of the Prince of Wales Hospital, the Chinese University of Hong Kong, during 1999-2000.
Scheduled for curative-intent radiotherapy
No distant metastases at diagnosis
No prior chemotherapy or other oncological therapy
Capacity to understand and to give consent

Exclusion Criteria:

Not described

Description of Study Protocol:

Recruitment From an oncology clinic, otherwise not described

Design Time series

Blinding used (if applicable) Not described

Intervention

Medical intervention
- Offered standard care of treatment for nutritional support which included:
  - Explanation of expected acute side effects of radiotherapy by the attending physcian
  - Group counseling sessions where nutritional advice was given prior to start of radiotherapy
  - Weekly assessment by a physician during radiotherapy
  - Encouraged to take milk supplements
  - Given analgesic and gargles to control oral pain
  - No specific limit on the use of nutritional support was instituted.
  - Prophylactic tube feeding was not offered.
- Radiotherapy
  - Standard curative course of radiotherapy given with total radiation dose ranging from 66-86 Gy
    - 2 Gy/day, 5 treatments per week, for 6.6-8.6 weeks
- Radiation port covered the whole of the nasopharynx, the oropharynx, the posterior half of the nasal cavities, most of the parotid glands and most of the submandibular glands throughout the treatment.
Study procedures
- Food intake was assessed
  - Reviewed by an interviewer with subject and food items and amounts were verified
  - Analyzed using food table
  - 24 hour recall was used to cross-check the accuracy of the food record
- Assessment of basal metabolic rate (BMR)
- Physical activity questionnaire
- Body weight and body composition measures
- Assessments were conducted at four time points:
  - Pre-radiotherapy (T₀)
  - End of radiotherapy (T₁)
  - 2 months post end of radiotherapy (T₂)
  - 6 months post end of radiotherapy (T₃)

Statistical Analysis

One way analysis of variance with repeated measures was performed to test the differences of the same variable across different time points.
Pearson's correlation was used to test the relation between various nutritional parameters and weight loss during end radiotherapy.

Data Collection Summary:

Timing of Measurements

	Pre radiotherapy	End radiotherapy	2 months post end radiotherapy	6 months post end radiotherapy
Height	x
weight	x	x	x	x
BMI	x	x	x	x
DXA	x	x	x	x
Food record	x	x	x	x
24 hour recall	x	x	x	x
BMR	x	x	x	x
Physical activity questionnaire	x	x	x	x

Dependent Variables

Food intake: assessed via a three day food record (2 weekdays/1 weekend day) during the week prior to an assessment visit
BMR: assessed via indirect calorimetry using a ventilated hood system under the following conditions:
- Measured in the morning after at least a 10 hour fast in a clinic room under quiet conditions
- Small amount of water was allowed before the measurement
- No vigorous physical activity was allowed
- Equipment was calibrated before measurement on each day
Total energy expenditure (TEE): assessed with a physical activity questionnaire used for a Chineese population
- Based on a modified Yale Physical Activity Questionnaire
- Covers occupational, general household, care taking, sports and leisure activities
Energy balance: determined by subtracting TEE measured by the physical activity questionnaire from energy intake estimated by the food record.

Independent Variables

Radiotherapy

Control Variables

Tumor stage
- Stage 0:Tis N0 M0
- Stage I: T1 N0 M0
- Stage IIA: T2a N0 M0
- Stage IIB: T2b N0 M0 or T1,T2a,T2b N1 M0
- Stage III: T3 N0,N1 M0 or T1,T2,T3 N2 M0
- Stage IVA: T4 N0,N1,N2 M0
- Stage IVB: Any T N3 M0
- Stage IVC: Any T Any N M1
Gender
Age

Description of Actual Data Sample:

Initial N: N=38 (30 males/8 females)

Attrition (final N): N=38

Age: Mean (range): 46 (33-71)

Ethnicity: not described

Other relevant demographics: not described

Anthropometrics

Overall stage
- Stage I and II: N=23
- Stage III and IV: N=15
Radiotherapy treatment dose
- <66 Gy: N=23
- 86 Gy: N=15
Commencing chemotherapy
- Yes: N=6
- No: N=32
BMI
- Mean (range) BMI was 24.2±3.9 (range 14.7-30.8)
- 66% were overweight (BMI > 23)
- 8% were underweight (BMI < 18.5)

Location: Oncology clinic at the Prince Wales Hosppital, The Chinese University, Hong Kong

Summary of Results:

Body Weight, BMI, Body Composition, and Weight Loss (mean±SD)

	Pre-Radiotherapy	End Radiotherapy	2 months post end Radiotherapy	6 months post end Radiotherapy
Body weight (kg)	63.3±11.4	56.5±10.9^a	55.7±10.3^a	55.5±9.5^a
BMI	24.2±3.9	21.5±3.7^a	21.3±3.4^a	21.16±3.2^a
Body fat (kg)	15.1±4.9	12.4±4.7^a	10.9±3.8^a,b	10.4±3.5^a,b
Body fat (%)	23.6±6.0	21.5±6.6^a	19.2±5.0^a,b	18.1±5.2^a,c
Lean mass (kg)	46.2±8.3	42.1±7.8^a	42.8±7.6^a,d	43.3±7.5^a,b
Lean mass (%)	73.5±5.9	74.9±6.3^e	77.2±4.8^a,b	78.1±4.7^a,c
%Weight loss (numbers)
>5		86.8 (33)	86.8 (33)	81.6 (31)
>10		52.6 (20)	65.8 (25)	63.2 (24)

^a P<0.001 vs pre-radiotherapy

^b P<0.01 vs end radiotherapy by ANOVA repeated measures

^c P<0.001 vs end radiotherapy by ANOVA repeated measures

^d P<0.05 vs pre-radiotherapy by ANOVA repeated measures.

^e P<0.05 vs end radiotherapy by ANOVA repeated measures.

There was a significant reduction in mean BMI at end of radiotherapy.
Body weight change from pre- to end of radiotherapy did not correlate with the BMI pre-radiotherapy.
The body weight at two and six months post-radiotherapy remained significantly lower than that pre-radiotherapy. Only half the subjects had weight increase between end of radiotherapy and six months post-radiotherapy.
Body fat mass and lean body mass at two and six months post-radiotherapy were significantly lower than pre-radiotherapy. During the time from end of radiotherapy to six months post-radiotherapy, lean body mass remained largely static, whereas body fat mass continued to decrease.
Subgroup analysis by age (<45 yr, n=19; >45 yr, n=19) did not show any didference in percentage of weight change between the two age groups, suggesting that age was a factor influencing weight loss.
Subgroup analysis by staging of disease at presentation (stages I and II, n=23; stages III and IV, n=15) showed no difference in percentage of weight change before and after radiotherapy.

BMR and TEE

	Pre-radiotherapy	End radiotherapy	2 months post end radiotherapy	6 months post end radiotherapy
BMR (kcal)	1406±204	1230±190^a	1220±195^a	1199±168^a
BMR/body weight (kcal/kg)	22.5±2.6	22.1±2.9	22.3±3.0	22.0±2.5
Bmr/lean body mass (kcal/kg)	30.7±3.0	30.0±3.4	28.7±3.6^b	28.0±2.4^a,c
TEE (kcal)	2494±729	1769±430^a	2012±448^a,c	2043±428^a,c

^a P<0.001 vs pre-radiotherapy by ANOVA repeated measures

^b P<0.01 vs pre-radiotherapy by ANOVA repeated measures

^c P<0.01 vs end of radiotherapy byANOVA repeated measures

There was a significant reduction in BMR at all the post radiotherapy time points.
For BMR per kg lean body mass, a significant decrease at two and six months post-radiotherapy was seen compared to pre-radiotherapy.
When BMR was corrected for body weight, no significant reduction was found.
A significant reduction in mean TEE was seen at the end of radiotherapy.
TEE increased singificantly between the end of radiotherapy and two and six months post-radiotherapy, although it did not return to the pre-radiotherapy level.

Calorie Intake

	Pre-radiotherapy	End radiotherapy	2 months post end radiotherapy	6 months post end radiotherapy
Calorie intake
Daily(kcal)	1857±411	1168±549^a	1960±544^b	1847±381^b
RDA (%)	77.0±14.9	48.9±23.5^a	81.6±21.3^b	77.3±16.8^b
Subjects with intake >80% RDA (%)c	36.8	10.5	47.4	39.5
BMRx1.5 (%)	88.6±18.7	64.5±31.4^d	107.7±25.8	103.7±21.2^b,e
Subjects with intake >80% BMRx1.5 (%)	63.2	26.3	84.2	94.7
Carbohydrate
Intake (g)	248±60	170±73^a	252±69^b	233±60.8^b
Kcal (%)	53.9±8.7	60.7± 11.7^e	52.2±7.6^f,g	50.5±8.9^b
Protein
Intake (g)	83±29	44±27^a	85±35^b	82±21^b
Kcal (%)	17.8±4.0	14.6±4.4^e	17.2±3.4^h	17.9±3.6^f
RDA (%)h	109.4±35.4	58.5±35.7^a	112.0±42.4^b	108.0±26.6^b
Fat
Intake (%)	59.9±19.9	35.1±24.6^a	66.8±23.9^b	63.7±18.2^b
Kcal (%)	28.8±5.9	24.9±9.7	30.4±5.5^h	31.1±6.1^h

^a P<0.001 vs pre-radiotherapy by ANOVA repeated measures.

^b P<0.001 vs end of radiotherapy by ANOVA repeated measures.

c 1988 Chinese RDA; 2200-2600 kcal for males and 1900-2300 for females, age and sex matched.

^d P<0.01 vs end of radiotherapy by ANOVA repeated measures.

^e P<0.05 vs end of radiotherapy by ANOVA repeated measures

^f P<0.01 vs end of radiotherapy by ANOVA repeated measures

^g 1988 Chinese RDA; 70-80 g for males and 65-70 g for females, age and sex matched.

^h P<0.05 vs end of radiotherapy by ANOVA repeated measures.

Significant decline in calorie intake was found between pre-radiotherapy and post-radiotherapy (P<0.001).
A significant increase in calorie intake was found between the end or radiotherapy and two months post-radiotherapy.
The calorie intake in the recovery period was not significantly different from pre-radiotherapy.
By completion of radiotherapy, 11% of subjects had energy intake >80% of the Chinese RDA. According to estimated energy requirements of cancer patients (BMR x 1.5), 26% had energy intake >80% of this estimated requirement at the end of radiotherapy.
At the end of radiotherapy, there was an increase in the percentage of energy derived from carbohydrate, a significant decrease in the percentage energy derived from protein, and a similar percent of calories derived from fat.

Energy Balance

Negative energy balance was found at both the pre-radiotherapy and post-radiotherapy time points, with an energy deficit of 600 kcal/day.
Weight loss was not significantly correlated with the magnitude of negative energy balance at pre-radiotherapy (r=0.166)
At 6 months post-radiotherapy, there was still a cumulative negative energy balance with a mean deficit of 200 kcal/day.
The magnitude of negative energy balance at the end of radiotherapy was significantly correlated with the body weight loss during the subsequent months.

Other Findings

Author Conclusion:

This study showed that nasopharyngeal cancer patients undergoing radiotherapy were at risk from malnutrition from negative nitrogen balance such that pretreatment body weight had still not been regained 6 months after the end of treatment.
Although there was preferential loss of body fat rather than lean mass, the health consequences of this loss are uncertain.
It is possible that there may be potential clinical and psychological consequences associated with this weight loss in the recovery period.
Further detailed assessment relating weight loss with clinical and psychological measurements may allow more definite conclusions to be drawn regarding the need for improved nutritional support during treatment of this disease.

Funding Source:

Industry:

Bristol Meyers Squibb Mead Johnson

Food Company:

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

No sample size calculation

Wonder how much wt loss occured prior to start of study. Energy deficit was present pre-radiotherapy.

Study partially supported by the Bristol-Myers squibb Mead Johnson Unrstricted Nutrition Grant

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?	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.)	No
	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?	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?		Yes
	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?	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?	Yes
	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?	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?	Yes
	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?		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)?	No
	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?	No
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