EAL

ONC: Radiation Therapy (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To review cases of patients affected by chronic radiation enteritis, free from malignancy, with clinical manifestation of an obstruction
To analyze overall survival amoung patients and long term nutritional autonomy in relation to treatment approach (surgery or HPN with bowel rest).

Inclusion Criteria:

Patients suffering from chronic radiation enteritis with intestinal obstruction
All patients must present with the following clinical manifestations of obstruction to include: vomiting, abdominal distention, inability to pass gas or stool, or diarrhea.
Radiological confirmation of severity of obstruction with the following signs at the abdominal x-ray: presence of air-fluid levels, intestinal bowel distention, intestinal wall edema, and absence of stool in the colon

Exclusion Criteria:

Patients with no follow up data
No clinical manifestations of obstruction
Persistent malignancy

Description of Study Protocol:

Recruitment

Initially, clinical history of 41 patients suffering from CRE were reviewed within 10 year time span
11 patients excluded
Thirty patients were included in the study
- 17 underwent surgery at first hospital admission
- 13 received HPN with or without surgery
  - 7/13 HPN only (54%)
  - 6/13 HPN followed by surgery (46%)

Design

1. Following factors were considered for each patient in the study:

Oncologic primary disease
Total dose of received radiation therapy
Time lapsed prior to onset of symptoms
Age at first signs of obstruction
Time between intital symptoms of obstruction and hospital admission
Severity of obstruction
Body mass index at diagnosis of obstruction
Number of risk factors for the development of enteritis.
- Risk factors were:
  - Age over 60 years old
  - Previous surgery
  - Concurrent chemotherapy and radiation therapy
  - Total dose of radiation therapy higher than 50 Gy
  - Presence of malnutrition, diabetes mellitus, hypertension and cardiovascular disease

2. Patients were then divided into two groups by which therapeutic approach they received first

Surgery group (S group) included 17 patients who underwent surgery first
HPN group included 13 patients who were first treated with bowel rest and HPN. Of this group, 7 were assigned to HPN only and 6 patients were assigned HPN and surgery.
- All patients received cyclic nocturnal parenteral nutrition via central line
- Calorie needs based on Harris-Benedict formula
- TPN included: 60-70% dextrose, 30-40% lipids, and protein was provided at 1-1.2 g/kg of body weight
- TPN also included: Daily MVI and weekly administration of fithomenadione, electrolytes and micronutrients added per each patient's assessed needs.
- TPN patients were monitored twice monthly
Patients were instructed on how to proceed from increasing kcals via oral intake while gradually reducing HPN
HPN patients were considered for surgery if symptoms of obstruction did not resolve and if there was no clinical or radiological improvement and patient could not resume oral intake

3. For each group, the following was studied: number of surgeries, post operative anastomatic leaks, duration of radiation enteritis symptoms, incidence and duration of HPN, dependence of HPN and overall survival.

Blinding used (if applicable)

N/A

Intervention (if applicable)

N/A

Statistical Analysis

1. Association between factors and treatment group were assessed using the following tests:

Wilcoxon rank sum test assessed factors represented by continuous variables
Fischer exact test assessed factors that were catagorical variables
Survival curves were analyzed using the Kaplan Meier method and compared by the log-rank test

2. Survival time was calculated from the date of inital symptoms to the time of death or evaluated at the final follow-up assessment in living patients.

Data Collection Summary:

Timing of Measurements

HPN patients monitored twice monthly on an outpatient basis
Overall survival in both groups measured at 5 years and 10 years follow up.

Dependent Variables

Number of subsequent surgeries (after first treatment)
Postoperative fistula
Total length (months) of HPN, mean (SD)
Persistence of obstructive symptoms
Nutritional autonomy
Mortality related to chronic enteritis

Independent Variables

Surgery at first hospital admission
HPN and intestinal rest
HPN and intestinal rest and surgery at a second stage

Control Variables

Description of Actual Data Sample:

Initial N: 41 patients with chronic radiation enteritis (31 females and 10 males)

Attrition (final N): 30 patients (23 females, 7 males)

Age: Surgery (N=17) 54.7 yrs old, HPN (N=13) 45.2 yrs old

Ethnicity: Italian

Other relevant demographics: none

Anthropometrics

BMI at beginning of treatment for Surgery group was 20.6 compared to BMI in HPN group at 17.5

Location: Milano, Italy

General Characterisitics of Patients in the Two Groups:

_______________________________________________________________________________

Variable Surgery(N=17) HPN(N=13) p value

_______________________________________________________________________________

Age 54.7(11.7) 45.2(13.0) 0.07

Gender 4 M/13 F 3 M/10F 1.0

Site of malignancy

Rectum 9 5 0.86

Uterus 5 4

Ovary 2 2

Other 1 2

Received dose(Gy) of RT,mean (SD) 51.5(4.5) 50.6(3.3) 0.48

Associated risk factors:

None 0 1 0.68

1 Factor 4 2

2 Factors 6 3

3 Factors 5 5

>/=4 Factors 2 2

Months before onset of symptoms after RT, mean (SD) 14.1(19.2) 17.2(24.1) 0.91

BMI(kg/m ²), at beginning of treatment, mean (SD) 20.6(3.0) 17.5(24.1) <0.01

Months between onset of symptoms and 2.3(2.3) 7.8(9.2) 0.01

admission to hospital mean (SD)

Number of radiological signs of obstruction:

1 Sign 4 2 0.50

2 Signs 4 3

3 Signs 8 6

4 Signs 1 2

BMI was the only measurement yielding a significant difference between the two groups
Duration of obstrutive symptoms is higher in the HPN group compared to the S group.

Summary of Results:

I. Surgery Data and Clinical Outcomes

Variables	S Group (N=17)	HPN (N=13)	p value
Number of subsequent surgeries none 1 Surgery >/= 2 Surgeries	10 (58.8) 5 (29.4) 4 (15.4)	7 (53.8) 6 (46.2) 0 (0.0)	1.00
Postoperative fistula	4 (15.4)	0 (0.0)	0.57
Total length (months) of HPN, mean (SD)	55.2(47.1)	19.3(18.0)	0.03
Persistence of obstructive symptoms	7(41.2)	4 (30.8)	0.71
Nutritional autonomy	10(58.8)	13 (100.0)	0.01
Mortality related to chronic enteritis	3(17.6)	0 (0.0)	0.

-Data above are numbers of patients(%).

-Percentages are calculated over the total number of surgeries(26 in the S group and 6 in the HPN group)

II. Summary of Results

In HPN group, 7 patients (53.8%) cleared the obstruction without the need for surgery and remaining required surgery after a mean of 12.7 months of nutritional support
In the S group, renewed surgical intervention was required in 41% of the patients
Anastomatic leakages were reported in 15.4% of the cases in the S group
In the S group, 10 patients developed intestinal failure secondary to short bowel after extensive surgery. These patient depended on HPN for survival with only 3 completely weaned from HPN.
Total time on HPN was 46 years in the S group and 21 years in the HPN group.
Two years following the diagnosis of chronic radiation enteritis, 10 members(58.8%) of the S group reached nutrition autonomy whereas all patients in the HPN achieved this.
Three deaths related to chronic enteritis in the S group died of cardiovascular failure.
68.4% of the S group and 90% of the HPN group achieved a five year survival. 90% over-all survival rate at 10 years in the HPN group

Other Findings

Central line infections were similar in the two groups.

Author Conclusion:

In more than half the cases, HPN and intestinal rest is preferred over early surgery in managing signs and symptoms of mechanical bowel obstruction due to radiation enteritis.
HPN appears to have a better survival rate as compared to early surgery.
Patients with chronic radiation enteritis are better able to achieve long term nutritional autonomy if initially treated with HPN and intestinal rest.

Funding Source:

Reviewer Comments:

Lack of randomization
Non-homogenous group of patients
Initially, 11 patients excluded
Calories based on Harris-Benedict formula
No mention of the quality of calories ingested amoung patients weaning from HPN
BMI alone was used in identifying nutritional status
BMI statistically lower amoung the HPN group as compared to the S group
No clear description of surgery, extent of resection etc
HPN compliance was not measured
Average HPN calorie intake would have been interesting to know
Suspect that protein needs should have been higher than 1-1.2g/kg in malnourished patients in HPN group

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?	No
3.	Were study groups comparable?		???
	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?	No
	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?	Yes
	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.)	Yes
	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?	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	???
	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?	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?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	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?		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?		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)?	N/A
	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?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		No
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes