EAL

ONC: Radiation Therapy (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The aim of this study is to determine whether supplementation with vitamins E (400 IU, three times per day) and C (500mg, three times per day) is beneficial in reducing symptoms of bleeding, diarrhea, fecal urgency and rectal pain resulting from chronic radiation proctitis.

Inclusion Criteria:

Eligible Patients

Received pelvic radiation treatment for gynecological or prostate malignancies
Had symptoms of rectal pain, bleeding or diarrhea with and without urgency
Had symptoms present for at least six months and had sought medical advice.

Diagnosis of radiation proctitis was confirmed by typical features of multiple telangiectasias and patchy friability seen by flexible sigmoidoscopy.

Exclusion Criteria:

None stated.

Description of Study Protocol:

Recruitment

20 consecutive symptomatic outpatients with endoscopically documented radiation proctitis seen in a single gastroenterology clinic.

Design

A convenient sample of 20 symptomatic patients with documented radiation proctitis were recruited
Patients were told to buy 500mg vitamin C and 400 IU vitamin A and take three times per day
Patients encouraged to eat high vitamin E foods and soy products
After a minimum of four weeks of treatment, patients were contacted by an investigator (not involved in their care) who conducted a telephone questionnaire regarding their symptoms before and after treatment
All patients treated for more than one year underwent a repeat questionnaire one year after the initial telephone contact regarding their present symptoms
Patient medical records were retrospectively reviewed to check whether patients' responses to the questionnaire were similar to those reported to their gastroenterologist during clinic visits.

Intervention

Patients were instructed to obtain over-the-counter vitamin C (500mg) and vitamin E (400 IU) and to take orally three times per day
Patients were encouraged to consume soy products and foods high in vitamin E
Patients already taking psyllium were asked to continue with their usual daily dose
5-aminosalicylic acid compounds, steroids and antidiarrheal agents were discontinued.

Statistical Analysis

The symptom index was compared before and after antioxidant therapy using the Wilcoxon rank test in all patients and between the first and second telephone interview (in those 10 patients who had two interviews)
Data are presented as median and range
P-values under 0.05 were considered significant.

Data Collection Summary:

Timing of Measurements

After a minimum of four weeks of treatment, patients were contacted by one of the investigators not involved in their care, who conducted an interview about symptoms before and after treatment
All patients who were treated for more than one year (N=10) underwent another telephone survey one year after the first, to determine if their response to treatment was sustained.

Dependent Variables

Four specific symptoms were assessed

Rectal bleeding
Rectal pain
Diarrhea
Fecal urgency.

The severity of each symptom was graded from zero (not present) to four (causing significant discomfort). The frequency of each symptom was also graded from zero(symptoms not occurring) to four (symptoms occurring daily). A symptom index was then developed by the addition of the severity score to the frequency score to achieve a maximum possible score of eight.

The effect of symptoms on lifestyle was also measured using the following scale:

Grade zero: Symptoms cause no effect on daily activity
Grade one: Symptoms cause inconveniences at least once a week
Grade two: Symptoms interfere with day-to-day activities more than once a week
Grade three: Symptoms interfere with activities on a daily bases
Grade four: Afraid to leave home, with significant restriction in social life.

Independent Variables

Over-the-counter supplement containing vitamin E (400 IU, three times a day) and vitamin C (500mg, three times a day)
Patients encouraged to eat a diet high in vitamin E and soy products.

Control Variables

Subjects serve as their own control.

Description of Actual Data Sample:

Initial N

N=20 (10 male, 10 female).

Attrition (Final N)

20 patients completed the intervention
10 patients (50%) were available for the one-year follow-up.

Age

10 men with prostate malignancy had a mean age of 77 (range, 62 to 86 years)
10 women with gynecological malignancies had a mean age of 64 years (range, 56 to 80)
17 had multiple symptoms.

Ethnicity

Not reported.

Anthropometrics

None reported.

Location

Chicago, Illinois.

Summary of Results:

Patient assessment of their symptoms during the telephone questionnaire was consistent with the recorded assessment of their clinic visits.

Symptom Indices Before and After Therapy

Symptoms	Symptom Index Before Therapy Median (range)	Symptom Index After Therapy Median (range)	P-Value
Bleeding	4 (0-8)	0 (0-7)	0.004
Diarrhea	5.5 (0-8)	0 (0-7)	0.001
Fecal urgency	6 (0-8)	3 (0-7)	0.001
Rectal pain	0 (0-8)	0 (0-8)	0.063

There was a significant (P<0.05) improvement in the symptom index before treatment vs. after treatment with vitamin C and E for bleeding (median score, four vs. zero), diarrhea (median score, 5.5 vs. zero) and urgency (median score, six vs. three)
Bleeding resolved in four of 11 patients. A significant reduction in the symptom index for diarrhea was found (resolved in eight of 16 patients): Diarrhea decreased in all patients except two with radiation ileitis; fecal urgency resolved in three of 16 patients and rectal pain resolved in two of six patients.
Lifestyle improved by at least one grade in 13 patients (65%), including seven patients who reported a return to normal lifestyle pattern
All patients who reported improvement with their symptoms noted this improvement by six weeks of treatment
At the one-year point, the 10 patients interviewed had no significant differences in bleeding, diarrhea and fecal urgency between the first and second interviews. The lifestyle improvement seen initially was also sustained one year later.

Author Conclusion:

Vitamin E and C appear to ameliorate the symptoms of rectal bleeding, diarrhea and fecal urgency, in addition to significantly improving patients’ lifestyle resulting from these symptoms
Data suggest that vitamin E and C are effective therapy for chronic radiation proctitis and may be a first line of treatment.

Funding Source:

Government:

USDA

Reviewer Comments:

Ethnicity of patients was not mentioned
Demographics and disease characteristics of the patients not described
Patients bought their own vitamin supplements, which could have been of varying quality
Investigators did not check patient compliance with supplementation
Patients encouraged to eat soy products and foods with a high vitamin E content, but there was no examination of dietary intake to assess this variable
There was no validation of the questionnaire used to collect symptom information
Information about symptoms both before and after treatment were collected at the same time, potentially introducing recall bias
Study was not blinded and no placebo was used
Sample size is very small
Follow-up was done on a convenient sample of those patients still being seen in the clinic after one year. There was no accounting for the other 50% of patients. This could be a source of considerable bias.

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?		No
	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?	No
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
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?	No
	4.4.	Were reasons for withdrawals similar across groups?	???
	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?	No
	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?		No
	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?	No
	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?	No
	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?	N/A
	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?		No
	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?	No
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	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?		N/A
	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?	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?	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