EAL

ONC: Radiation Therapy (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate and describe the clinical symptoms, functional changes and nutritional changes after five weeks of external pelvic radiation

Inclusion Criteria:

Female patients
Gynecological neoplasm
Receiving external pelvic irradiation
Total dosage 45-50 Gy using four-field box technique

Exclusion Criteria:

Diabetes mellitus
Chronic renal failure (s. creatinine >2mg/dl)
Liver or cardiac failure
Other cancers
Chronic diarrhea
Intestinal or gastric resections
Previous radiation treatments

Description of Study Protocol:

Recruitment: Not Described

Design: Following consent, enrolled patients were following during the five week period of radiotherapy. Information on body composition, dietary intake, resting energy expenditure, laboratory values, and symptoms were obtained during and immediately after the five week radiation treatment period.

Blinding used (if applicable): Not applicable

Intervention (if applicable): Not applicable

Statistical Analysis: Not described

Data Collection Summary:

Timing of Measurements

Baseline and 5 weeks (completion of radiation):

Nutritional Status as measured by Subjective Global Assessment (SGA)
Clinical Symptoms [on a 0 (absent) to 3 (severe) scale]
Medications
Nutrient Intake as measaured by 24-hour recall
Percent Body Fat as calculated with the Durnin and Womersley equation from the following:
- Weight
- Height
- Skinfold Thickness
Arm circumference
Waist and hip circumference
Muscle grip strength as measured by hand grip dynamometer
Body fat mass and Fat free mass as measured by DXA
Resting Energy Expenditure (REE) by indirect calorimetery in a canopy system
Clinical Laboratory Tests
- Blood Cell Count
- S. Glucose
- Creatinine
- Blood Urea Nitrogen
- Total Protein
- Albumin
- Total Bilirubin
- Hepatic Aminotransferases
- Total Cholesterol
- Triglycerides
- Uric Acid
- Electrolytes
Gastric Permeability as measured by urinary lactulose/mannitol & sucrose excretion tests
Orocecal Transit Time as measured by hydrogen breath test (post lactulose ingestion)
Jejunal biopsies

Throughout study period:

Clinical Symptoms [on a 0 (absent) to 3 (severe) scale]

Medications

Dependent Variables

Variable 1: Nutritional changes as measured by nutrient intake, REE, laboratory values and body composition
Variable 2: Functional changes as measured by muscle strength and body composition
Variable 3: Morphological intestinal changes as measured by jejunal biopsies

Independent Variables

Amount of pelvic radiation received

Description of Actual Data Sample:

Initial N: 15 (0 males, 15 females)

Attrition (final N): 15 (0 males, 15 females)

Age: Range: 27-60

Ethnicity: Not Described, however one can assume primarily hispanic due to the location of the study (Santiago, Chile)

Other relevant demographics:

Tumor Type:

Cervical carcinoma: n=10
- St IB: n=5
- St IIB: n=3
- St IIIB: n=2
Endometrial adneocarcinoma: n=3
- St IC: n=2
- St II: n=1
Uterine rabdomiosarcoma: n=1
Vaginal cupula invasive carcinoma: n=1

Anthropometrics

BMI: 26.8kg/m2 ± 5.0
Arm Circumference: 29.8 cm ± 3.7
Body Fat: 36.1% ± 5.8

Location: Fundacion Arturo Lopez Perez National Cancer Center, Santiago , Chile

Summary of Results:

Nutritional Parameters During Treatment

Anthropometrics	Before (Mean ± SD)	After (Mean ± SD)	Paired t-test (p)
BMI (kg/m2)	26.8 ± 5.0	26.5 ± 5.0	0.02
Arm Circumference (cm)	29.8 ± 3.7	29.4 ± 4.1	0.04
Body Fat (%)	36.1 ± 5.8	35.0 ± 6.0	0.05
Handgrip Muscle Strength (kg)	26.4 ± 4.9	26.3 ± 4.4	0.04
DXA
Total Mass (kg)	62.3 ± 13.3	61.6 ± 13.6	0.03
Fat Free Mass (kg)	37.8 ± 5.6	36.7 ± 5.6	0.005
Fat Free Mass (%)	65.3 ± 6.5	64.3 ± 6.7	0.06 (NS)
Fat Mass (kg)	22.2 ± 8.5	22.6 ± 8.5	0.14 (NS)
Fat Mass (%)	34.7 ± 6.5	35.7 ± 6.7	0.06 (NS)
Bone Mineral Content (g)	2209.2 ± 330.3	2200.3 ± 338.0	0.32 (NS)

Energy Expenditure and Caloric Intake

	Before (Mean ± SD)	After (Mean ± SD)	Paired t-test (p)
Caloric Intake (kcal/d)	2143.5 ± 799.2	1829.7 ± 1192.6	0.18 (NS)
REE (kcal/d)	1672.6 ± 487.9	1585.0 ± 274.9	0.05
REE/FFM (kcal/kg)	44.4 ± 12.0	43.3 ± 4.1	0.22 (NS)
RQ	0.7 ± 0.2	0.7 ± 0.05	0.33 (NS)

Intestinal Permeability

	Before (Mean ± SD)	After (Mean ± SD)	Paired t-test (p)
Mannitol (%)	14.5 ± 4.8	11.8 ± 4.4	0.061 (NS)
Lactulose (%)	0.4 ± 0.3	0.7 ± 0.6	0.042
Sacarose (%)	82.6 ± 72.6	91.0 ± 96.1	0.353 (NS)
Lactulose/Mannitol	0.030 ± 0.019	0.064 ± 0.062	0.027

Other Findings

Nutritional:

Nutritional Status
- Baseline: SGA-A (well nourished) n=10; SGA-B(moderate/risk of malnutrition) n=5
Caloric Intake
- Stable throughtout study
Whole body REE average 125% of Harris Benedict Calculation

Laboratory:

Baseline most laboratory values WNL
- Low hematocrit: n=5
Post-radiation:
- Hematological parameters decreased significantly
  - Hct (p=0.02)
  - Plt (p=0.001)
  - Leuc (p=0.0003)
  - Lymph (p=0.0002)
- Cholesterol decreased significantly (p=0.015)
- Triglycerides increased significantly (p=0.019)

Functional:

Intestinal orocecal transit time decreased after 5 weeks radiation (p=0.05)
- This occured more in patients that had a history of surgical treatment (p=0.05)
Significant changes in histology
- Longer vili
- Several crypts opening into one villus

Symptoms:

Most patients developed GI symptoms
- Diarrhea: n=13 (lasting 2-13 days)
- Abdominal pain: n=12
- Nausea: n=1
Urological complaints: n=12
- Positive urine cultures: n=4
Diarrhea managed with 6mg loperimide, fiber restriction, oral hydration

Author Conclusion:

Pelvic radiation therapy to treat gynecological neoplasms causes acute changes in small bowel function. These changes are associated with nutritional deterioration.

Funding Source:

University/Hospital:

University of Chile, Institute of Nutrition and Food Technology

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

This study provides much needed pilot data describing the impact of pelvic radiation on nutritional status. The study is limited by the following:

No control (non-radiation) group
Limited number of subjects
No description of statistical methods
No objective measures presented for histological assessments

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?	N/A
	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?		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.)	N/A
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	No
	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?	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.)	No
	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?	N/A
	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?	Yes
	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?		No
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	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?	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)?	???
	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?	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?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes