EAL

ONC: Radiation Therapy (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess the frequency of nutritional consequences of tumors of the head and neck before and during radiotherapy.
To study the impact of nutritional supplementation in patients with head and neck cancer treated with radiotherapy on treatment delay and mucosal reaction.

Inclusion Criteria:

Patients with head and neck cancer who were prospectively referred for radiotherapy.
All patients were scheduled to receive conventional irradiation (radical or postoperative) with ⁶⁰Co teletherapy equipment.

Exclusion Criteria:

None noted

Description of Study Protocol:

Recruitment

A convenience sample of patients with head and neck cancer who were prospectively referred for radiotherapy
No time frame for recruitment period was reported.

Design

Patients were randomized, regardless of pre-treatment nutritional status, to receive either:
- Radiotherapy alone
- Radiotherapy plus oral nutritional supplementation

Blinding used (if applicable)

None reported

Intervention (if applicable)

Oral nutritional supplementation was prescribed for 10-15 days before therapy for malnourished patients, OR
After receiving a dose of 32-34 GY up to 46-50 GY for all patients, OR
For patients treated with radical radiotherapy, an additional course might be considered

Statistical Analysis

Methods not described

Data Collection Summary:

Timing of Measurements

Subjective nutrition assessment

Before start of radiotherapy
Weekly for 6 weeks druing therapy

Objective nutrition assessment

Before start of radiotherapy
Weekly for 6 weeks during therapy

Scoring of normal tissue reaction

Weekly for 6 weeks during therapy

Dependent Variables

Variable 1: Subjective nutrition assessment--questionnaire dealing with awareness of mouth dryness, patterns of fluid intake, taste changes, dysphagia, appetite loss and food preferences
Variable 2: Objective nutrition assessment --weight (kg), height (cm), mid-arm muscle circumference, triceps skin-fold measurement, percentage weight loss
Variable 3: Scoring of normal tissue reaction according to the following table

Functional Mucosal Reaction
0	No symptoms, normal diet
I	Mild discomfort, normal or semisolid diet
II	Severe reaction, liquid diet, treatment not stopped
III	Treatment stopped and/or oral alimentation not possible
Objective mucosal reaction
0	No reaction
I	Erythema
II	Patchy mucositis
III	Intense confluent mucositis

Independent Variables

Oral nutritional supplementation with high-protein nutritional powder (Ensure, Abbott Laboratories) in an amount estimated using the equation:
- Calories to be provided from Ensure = Calorie need [estimated as weight (kg) x 20 +1100 Cal] -calorie intake [estimated from a 3-day diet diary]

Control Variables

Description of Actual Data Sample:

Initial N = 23

Attrition (final N): All subjects completed the study

Location: Kasr El-Eini Center of Oncology and Nuclear Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt

Demographics from Table II, pg 14 of the study article.

	Radiotherapy alone	Radiotherapy + Ensure	Total
N (m/f)	9/3	8/3	17/6
Age (range/median)	35-75/50	29-29/48	29-79/49
Primary tumor site
nasospharynx	2	3	5
tonsil	2	1	3
oropharynx	0	1	1
cheek	1	0	9
Malnourished prior to radiotherapy	3	3	6

Summary of Results:

Independent variable: Regimens of Nutritional Supplementation

The 3 malnourished patients in the radiotherapy plus nutritional supplementation group received 1 course of supplements before or at the beginning of the course of irradiation
All 11 patients in the radiotherapy plus nutritional supplementation group received a course of supplementation after a dose of 32-34 up to 48-50 GY according to the patient's condition and/or mucosal reaction.
2 patients received an additional course of supplementation.
In total, patients received 1500-2000 Cal/d from supplementation.

Dependent variable: Subjective Nutrition Assessment

Prior to radiotherapy, no patient in either group was subjectively aware of dry mouth.
17% of patients reported changes in taste and loss of appetite prior to radiotherapy; by week 5, 70% of patients were aware of these problems
There was no difference between groups in regard to frequency of subjective awareness of dry mouth, changes in taste, or loss of appetite

Dependent variable: Objective Nutrition Assessment

Prior to radiotherapy, 6 of the 23 patients (23%) were malnourished.
All patients in the radiotherapy plus nutritional supplementation group increased body weight (median increase = 5%), mid arm circumference and triceps skinfold (median increase = 4%)
The 3 malnourished patients in this group showed the maximum % increase in body weight
In the radiotherapy group, 58% of patients lost weight (median decrease = 2%)
33% of patients in the radiotherapy group had decrease in mid-arm circumference and triceps skinfold (medican decrease = 1%).
Diferences in anthropometric measurements between the groups were statistically significant (p=0.001).

Dependent variable: Mucosal reaction

No patient in the radiotherapy plus nutritional supplementation group had grade III mucosal reaction
33% of the patients in the radiotherapy group had Grade III functional mucosal reactions
25% of patients in the radiotherapy group had Grade III objective mucosal reactions
25% of patients in the radiotherapy group had peak mucosal reaction for >2 weeks; 9% of these received nutritional supplementation
Differences were not statistically signficant
Treatment had to be suspended for 5 patients in the radiotherapy group; <10 days for 4 and 2 weeks for 1 patient
Treatment was not suspended for any patients in the radiotherapy plus nutritional supplementation group

Other Findings

Generally, carbohydrate, especially sugar, contributed a greater % to total caloric intake, whereas protein, especially meat, were avoided by most of the patients late in therapy.

Author Conclusion:

Head and neck tumors compromise nutritional status prior to and during radiotherapy by affecting normal tissues in and around the oral cavity. The frequency of nutritional problems increased with doseage of irradiation. Nutritional supplementation helps patients complete full course and dose of radiation therapy. Patients who receive nutritional supplementation have mucosal reactions to lesser degrees than the control group.

Funding Source:

University/Hospital:

Cairo University

Reviewer Comments:

This study is 14 years old and was completed without the methodological rigor expected of more modern studies.
The sample size is small, without description of a power study to justify the size.
This is a difficult population to study. Would failure to provide nutritional support to this patient population even be possible today?
This study is valuable in its support of the reaction to provide nutritional supplementation in this high risk population. However, most findings do not achieve statistical significance. This does not deny the potential importance of the clincial significance of the findings.

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?	???
	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?	Yes
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)	No
	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?		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?		???
	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?	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?	No
	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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	???
	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?	???
	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?	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