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ONC: Radiation Therapy (2007)

Citation:

Pia de la Maza M, Agudelo GM, Yudin T, Gattàs, Barrera G, Bunout D, Hirsch S. Long -term nutritional and digestive consequences of pelvic radiation.Journal of the American College of Nutrition 2004;23(2): 102-107. 

 
Study Design:
Time Study
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To study the long-term nutritional (lean body mass preservation/fat gain prevention) and digestive changes in 15 women previously treated with radiotherapy for gynecological cancer. This research was the third assessment of this group of patients.
Inclusion Criteria:

        

  • Nineteen patients that were treated with pelvic external radiotherapy, plus intracavitary radiotherapy (ICRT) or surgery two years prior, for gynecological cancer at a national cancer institution (Fundació Arturo López Pérezin Santiago, Chile).
  • These same patients had participated in a study about the effects of pelvic radiation on digestion and nutritional parameters.
  • Each patient agreed to participate in this 3rd follow-up ,only if the small bowel biopsies was not repeated again, by signing a written informed consent.
Exclusion Criteria:
Exclusion Critera were not detailed.
Description of Study Protocol:

Recruitment : Women treated with XRT for gynecologic malignancy in Chile were recruited for this study. Nineteen patients were recruited, but only 15 patients participated in the two-year follow-up.

Design : Time series with assessment of participants before XRT, immediately after, and two years post XRT.

Blinding used -NA

Intervention -N/A

Statistical Analysis :

  • Normally distributed variables on three occassions were analyzed by Anova for repeat measures.
  • Nonparametric variables were analyzed through Wilcoxon paired test or Friedman's xr2 for repeated series.
  • A logistic regression model was employed to explain occurrrence of GI system during the three periods analyzed.

 

    

Data Collection Summary:

Timing of Measurements:

  • Time 1: Before external radiology
  • Time 2: At the fifth week of external radiation (completion of treatment)
  • Time 3: Two years after external radiation

Dependent Variables

  • Nutritional Status- lean body mass preservation/fat gain prevention
  • Gastrointestinal functions-Indicators of intestinal function included a semiquantitative recollection of gastric symptoms(including vomiting, diarrhea,abdominal distention, pain ,bloody diarrhea,and rectal complaints,such as urgency,tenesmus,and rectal bleeding),measured intestinal transit velocity by the lactulose breath test and gastrointestinal permeability by the urinary excretion of ingested lactulose,manitol and sucrose.

 

 

Independent Variables

  • Clinical Evaluation-included validated dietary records,daily physical activity record.    
  • Laboratory parameters -fasting blood sample was drawn to provide routine clinical laboratory tests(hemoglobin,white blood cell count,creatinine,lipoproteins,glucose,total proteins,albumin, and C reactive protein), using automated methods with kits from Abbott.
  • Anthropometry -Body composition was assessed by classical anthropometric measures and double beam x ray absorbtiometry(DEXA) in a Lunar DPX-L densitometer.
  • -As an additional nutrition al indicator, grip muscle strength was measured(hand dynamometer model 0032,by Therapeutic Instruments )
  •  Energy Balance: (1) Resting energy(REE) was measured by indirect calorimetry,according to standard techniques(Sensor Medics model 2900 calorimeter).   (2)Total energy expenditure(TEE) was calculated as REEx energy cost of various activities,obtained from the daily physical activity recalls.
  • Energy Cost: The energy cost total activities were calculated according to FAO/WHO/UNU 1985.

Control Variables-not applicable

 

Description of Actual Data Sample:

 

Initial N: 19 females

Attrition (final N): 15 females: three(3) patients died; one(1) declined to participate for personal reasons.

Age: 48.9±9.8 years

Ethnicity: Chilean women.

Other relevant demographics:

  • The average external radiation dose 45-50 Gy,delivered by a Cobalt-60 Unit(phoenix 80,SSD 80 cm) using the 4-field box technique. The total dose was fractioned in 180-200 cGy per day,during five weeks.
  • Seven patients had been operated on prior to radiotherapy (hysterectomy plus oophorectomy).
  • Fourteen received ICRT (10-15 Gy) after completing external radiation.
  • Seven (7) of the 15 patients were menopausal before cancer treatment, eight (8) became menopausal thereafter.
  • At Time 3 assessment, five of the fifteen patients were on irregular hormonal replacement therapy.
  • Physical examinations were normal in all cases, without tumor replacement.

Anthropometrics (e.g., were groups same or different on important measures)NA

Location: University of Chile, Arturo LÓpez-Pérez Foundation, Santiago, CHILE.

 

Summary of Results:

 

Table 1: Most laboratory parameters were within normal ranges during the 3 assessment periods,except for serum lipid levels. At Times 2 and 3 , hemoglobin and total proteins increased compared to basal values,however a radiation induced fall in white blood cells count persisted with a definite leukopenia in 3 patients. 

Table 1. Laboratory Parameters during Follow-Ups
 

Time 1

Time 2

Time 3

p
Hematocrit

0.37±0.48

0.37±0.42a

0.39±0.27ß

0.01
Hemoglobin(g/L)

124±19

122±15a

134±09ß

0.01
Erythrocyte Sedimentation Rate(mm/h)

25.0±18.5

30.6±19.6

20.2±12.9

0.22
White Blood Cell Count(109/L)

9.4±7.6ß

3.9±1.1a

4.6±1.2

<0.01
Glucose(mmol/L)

5.1±0.34

5.3±0.48

4.94±0.82

0.26
Creatinine(umo/L)

61.9±26.5

61.9±8.84

70.7±8.84

0.72
Total Proteins(g/L)

75±7a

76±8

81±5ß

0.01
Albumin(g/L)

42±4

44±3

43±2

0.08
Total Cholesterol(mmol/L)

5.3±1

4.9±0.9a

5.6±0.6ß

0.04
Triglycerides(mmol/L)

1.4±0.5a

1.9±0.9

1.8±0.7ß

0.01

aß=significantly different by Sheffeé post-hoc analysis.Results are expressed as mean±standard deviation.

 

 

Table 2: A significant increase in body mass index(BMI) and waist circumference was observed after 2 years. In contrast,hand grip strength decreased in parallel, although not significantly.

Table 2.Nutritional Status Assed by Anthropometry
 

Time 1

Time 2

Time 3

p
Weight(Kg)

64.9±13.4a

64.4±13.1

69.1±15.2ß

<0.01
BMI(Kg/m2)

27.3±4.8a

27.0±4.8

28.5±5.8ß

<0.01
Waist(cm)

84.9±10.6a

85.2±10.9

88.5±10.8ß

<0.01
Hip(cm)

99.5±9.5

98.9±8.9a

101.4±7.0ß

0.03
Handgrip Strenght(Kg)

27.4±4.99

26.6±4.3

25.1±3.7

0.09

aß=significantly different by Sheffeé post-hoc analysis. Results are expressed as mean±standard deviation.

 

Table 3: Changes in body composition were confirmed by DEXA,which showed a significant increase in body fat and contraction of the fat-free compartment in Time 3,compared to previous examinations.

Table 3. Nutritional Status Assessed by Double Beam X-Ray Absorptiometry
 

Time1

Time 2

Time 3

p
Total Mass(Kg)

64.2±13.3

63.5±13.2a

68.5±15.7ß

<0.01
Fat Free Mass(Kg)

38.7±5.7

37.7±5.9

38.6±6.2

0.05
Fat Free Mass(%)

64.7±6.6ß

63.7±6.5

60.2±4.3a

<0.01
Fat Mass(Kg)

23.3±8.8a

23.6±8.5

27.7±10.4ß

<0.01
Fat mass(%)

35.3±6.6a

36.3±6.5

40.0±5.2a

<0.01
Bone Mineral Content(g)

2216±372

2210±380

2166±308

0.82

aß=significantly different by Sheffeé post-hoc analysis.                                                                                             Results are expressed as mean±standard deviation.

 

Table 4: Energy expenditure(REE and REE/FEE) decreased significantly in this third evaluation compared with previous measurements. Physical activity was classified as sedentary throughout the study, and the calculated TEE declined progressively.

Table 4:Energy Expenditure During Follow-UP
 

Time 1

Time 2

Time 3

p

REE(Kcals/day)

1695±231a

1644±292a

1286±175ß

<0.01

REE/FFM(Kcals/day)

43.9±3.5a

43.8±4.1a

3.3±2.8ß

<0.01

TEE(Kcals/day)

2255±345a

2134±353a

1686±335ß

<0.01

REE=Resting Energy Expenditure;TEE=Total Energy Expenditure;FFM=Fat Free Mass

aß=significantly different by Sheffeé post-hoc analysis.                                                                 Results are expressed as mean±standard deviation.

 

Table 5:The ingestion of energy,protein,fat and vitamin B12 increased significantly 2 years after completion of cancer treatment compared with other periods. The ingestion of several micronutrients (thiamine,tocopherol,pyridoxin,folic acid)and fiber remained below the RDAs (note- source of RDAs not cited).

Table 5: Dietary Ingestion Throughout the Study
 

Time 1

Time 2

Time 3

p
Energy(Kcals)

2054±752

1580±670a

2336±945ß

0.01
Protein(g)

66.9±29.4

51.2±21.4a

87.8±41.4ß

<0.01
Fat(g)

55.1±28.9

34.2±16.4a

81..4±43.1ß

<0.01
Carbohydrate(g)

323.5±114.8

264.9±131.6

316±154

0.35
Fiber(g)

5.6±3.0

4.2±3.2

5.7±2.9

0.38
Thiamine(mg)

1.5±1.1

1.1±0.7

1.4±0.8

0.27
Riboflavin(mg)

1.2±1.0

1.0±0.9

1.7±1.2

0.01
Niacin(mg)

12.1±7.6

9.0±4.5

13.6±7.1

0.10
Pyridoxin(mg)

1.1±1.0

0.8±0.6

1.3±0.5

0.17
Vitamin E(mg)

1.4±0.6

0.8±0.5

1.1±0.9

0.01
Vitamin C(mg)

123±161

102±153

58±39

0.34
Vitamin A(UI)

1241±358

856±1104

886±1203

0.49
Vitamin B12

3.0±3.1

2.0±1.8a

4.7±3.3ß

0.01
Folate(mcg)

168±92

142±92

150±104

0.69
Calcium(mg)

559±307

426±242

741±865

0.27

aß=significantly different by Sheffeé post-hoc analysis.                                                                                            Results are expressed as mean±standard deviation.

 

Other Findings:

Digestive symptoms-

  • Patients mainly complained of diarrhea immediately after radiation therapy.
  • Abdominal bloating(12 patients) and rectal symptoms such as a rectal bleeding and tenesmus(8 patients),prevailed 2 years later.
  • Bowel habits remained unchanged in 6 cases,while 9 women experienced definite changes.
  • In 5 cases a "correction" of previous constipation occurred,2 women developed mild intermittent chronic diarrhea, and two others presented  with moderate diarrhea(frequent and painful episodes of liquid stools,which interfered with daily life).
  • Surgery prior to radiation did not affect the occurrence of these symptoms.

Intestinal permeability and transit time-

  • At Time 3,intestinal permeability and transit time were lower than values at     Time 1,but still within normal range.
  • According to the logistic regression model,neither intestinal transit time nor intestinal permeability explained gastrointestinal symptoms(diarrhea and abdominal distension),and these were not associated with nutritional parameters.
Author Conclusion:
  • The authors reported that the main finding of this study was the significant gain of body fat,despite the high protein ingestion,observed after radiotherapy for gynecological cancer,together with a lack of recovery of the lean tissue lost during the treatment period.
  •  The authors noted that discrepancy with other studies on radiation complications was probably due to case selection : malnutrition is often detected in patients requesting medical assistance due to severe actinic complications, such as ulcerations and fistulae.
  • Changes in body composition were confirmed by DEXA,which showed a significant increase in body fat and contraction of the fat-free compartment in Time 3,compared to previous examinations.

  • Digestive symptoms:

    • Patients mainly complained of diarrhea immediately after radiation therapy.
    • Abdominal bloating(12 patients) and rectal symptoms such as a rectal bleeding and tenesmus(8 patients),prevailed 2 years later.
    • Bowel habits remained unchanged in 6 cases,while 9 women experienced definite changes.
    • In 5 cases a "correction" of previous constipation occurred,2 women developed mild intermittent chronic diarrhea, and two others presented  with moderate diarrhea(frequent and painful episodes of liquid stools,which interfered with daily life).
    • Surgery prior to radiation did not affect the occurrence of these symptoms.
Funding Source:
University/Hospital: University of Chile, Institute of Nutrition and Food Technology
Reviewer Comments:
  • The RDA was noted in the study but the reference was not cited. It is unknown if the RDA refers to American or Chilean standards.
  • Validated dietary records and daily physical activity records - methodology was not detailed in this  journal article but were referenced.
  • The study was conducted on a limited sample size leading to restricted power.
  • The intake of high protein and its role in weight gain does not seem to be clearly defined /understood especially in reference to the statement,"significant gain of body fat,despite the high protein ingestion."
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) N/A
  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) N/A
 
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? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  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? 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%.) Yes
  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? N/A
  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? 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? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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? No
  7.1. Were primary and secondary endpoints described and relevant to the question? No
  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? N/A
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? No
  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)? 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? No
  10.1. Were sources of funding and investigators' affiliations described? No
  10.2. Was the study free from apparent conflict of interest? Yes