ONC: Radiation Therapy (2007)


­­­­­­­­­­­­­­­­Hearne BE, Dunaj JM, Strong EW, Vikram B, LePorte BJ, DeCosse JJ. Enteral nutrition support in head and neck cancer: Tube feeding vs. oral feeding during radiation therapy. Journal of the American Dietetic Association. 1985 June; 85 (6): 669 – 74, 677.

PubMed ID: 3923081
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
The purpose of the study was to compare intensive nasoenteric tube feeding with optimal oral nutrition in patients with advanced head and neck cancers during intensive outpatient radiation therapy, to determine the effectiveness of each by measuring nutritional and performance status during therapy.
Inclusion Criteria:
  • Stage III or IV unresectable cancer of the nasopharynx, larynx, oropharynx, hypopharynx, or oral cavity (including recurrence)


Exclusion Criteria:
  • Not mentioned
Description of Study Protocol:


  • Not specifically mentioned; however, all study participants were patients receiving radiation therapy at the same cancer treatment center


  • 31 patients were randomized to receive either oral or tube feeding during outpatient radiation therapy
  • Patients were stratified:
    • By site
    • By first treatment (chemotherapy alone; chemotherapy plus radiation therapy; radiation therapy alone)
    • By previous head and neck surgery (yes or no)
  • A registered dietitian interviewed each incoming patient to assess:
    • Baseline nutrition history
    • 24-hour recall using food models
    • Weight, height, and mid-arm circumference
    • Baseline serum albumin
    • Performance status
    • Taste changes
    • Toxic responses to treatment, including diarrhea, constipation, dysphagia, xerostomia, mucositis, nausea, vomiting
  • Following randomization, and based on dietitians' nutrition assessment, a nutrition care plan was devised for each patient
    • Kcal goal was 40 kcal/kg and 1.0 g pro/kg
    • Patients randomized to oral intake were provided with nutrition counseling to achieve intake goals
      • Oral supplements were provided for patients unable to meet nutrition goals by food selections
      • Kcal and protein goals were adjusted by 5 kcal/0.2 g pro increments when target intake did not maintain body weight within 1 kg
    • Tube fed patients were provided with a commercial isotonic, isocaloric formula
      • Tube feeding was implemented along with oral intake to achieve kcal and protein goals
      • Patients were instructed in method for administering formula
        • Patients could choose long-term tube placement, could learn to pass the tube themselves for feedings, or could opt for continuous nocturnal feedings
      • Patients received full-strength feeding, with maximum feeding volume of 500 ml, with at least 4 hours between feedings
        • 6 patients were changed to a high caloric density formula during the study period
  • Both groups of patients received radiation therapy for 6-8 weeks
    • Mean dosage for oral group was 6,500 rads; mean dosage for tube fed group was 6,700 rads
    • Mean field size for tube fed group was 158 cm2 vs 111 cm2 for the oral feeding group
      • Difference may have been due to greater number of Stage IV cancers in tube fed group
  • Study dietitians saw each patient bi-weekly during radiation therapy to assess and evaluate patients
  • At end of radiation therapy, tube-fed patients were returned to oral feedings unless continued tube feeding was medically indicated
  • Patients were followed for two years after therapy or until death

Blinding used (if applicable): 

  • Not mentioned

Intervention (if applicable):

  • Tube feeding vs. oral feeding

Statistical Analysis:

  • Statistical analysis was not discussed
  • Data was not analyzed on an intent-to-treat basis


Data Collection Summary:

Timing of Measurements:

  • At study outset, the following measurements were taken:
    • Baseline nutrition history
    • 24-hour recall using food models
    • Weight, height, and mid-arm circumference
      • Used method of Durnin and Womersley
      • Used study-certified scale
      • Used Lange calipers
    • Baseline serum albumin
    • Performance status
      • Karnofsky Performance Scale, rated on a 0 - 100 scale
    • Taste changes
      • Assessed as normal, partial loss, or complete loss
      • Patients experiencing partial taste loss were assessed for description of the taste problems, such as meat aversion, metallic taste, or sweet intolerance
    • Toxic responses to treatment, including diarrhea, constipation, dysphagia, xerostomia, mucositis, nausea, vomiting
      • Toxic responses were graded using a scale developed specifically for the study by the study dietitians, radiotherapist, and head and neck surgeons
        • Toxicities were graded on a 0-4 scale, with 0 = no toxicity, 1 = slight toxicity, 2 = moderate toxicity, 3 = severe toxicity, 4 = life-threatening toxicity 
  • The following measures were evaluated weekly: 
    • Toxic responses to treatmentPerformance status (Karnofsky Performance Scale)
    • Weight (Study-certified scale)
    • 24-hour dietary recall (administered by a registered dietitian)
  • Serum albumin, triceps skinfold, and mid-arm circumference were evaluated at study outset, week 4, end of therapy, and 1 month following radiation therapy
  • Patients were followed for two years after therapy or until death

Dependent Variables

  • Body weight
  • Treatment toxicities 
  • Caloric intake during therapy
  • Protein intake during therapy
  • Serum albumin 

Independent Variables

  • Oral feeding
  • Tube feeding

 Control Variables

  • Advanced head and neck cancer
  • Radiation therapy


Description of Actual Data Sample:

Initial N:

  • N = 31 (24 male, 7 female)
    • Tube feeding group = 18 (15 male, 3 female)
    • Oral group = 13 (9 male, 4 female)

Attrition (final N):

  • Tube feeding group: Number evaluated = 14
  • Oral group:  Number evaluated = 12
  • For both groups:
    • 2 patients chose treatment at other cancer centers
    • 1 patient was found ineligible by site after randomization
    • 1 patient died during pre-radiation chemotherapy
    • 1 patient was eliminated from study due to a gastrectomy
  • Violators
    • 2 patients randomized to the tube-fed group refused tube feeding and were orally fed
    • 2 patients randomized to the oral group dropped to <80% IBW within first week of study and were tube fed
    • Data of violators was analyzed with their actual treatment groups


  • Tube fed group: 52.1 (22-74) years
  • Oral group:  56.1 (37-83) years


  • Not mentioned

Other relevant demographics:

  • Cancer site:
    • Tube fed group: Nasopharynx = 5; all others (including recurrent nasopharynx) = 13
    • Oral group: Nasopharynx = 4; all others (including recurrent nasopharynx) = 9
  • First treatment:
    • Tube fed group: Chemotherapy with radiation therapy = 6; radiation therapy alone = 12
    • Oral group: Chemotherapy with radiation therapy = 2; radiation therapy alone = 11
  • Clinical stage:
    • Tube fed group: Stage III = 4; Stage IV = 14
    • Oral group: Stage III = 7; Stage IV = 6
  • Ability to swallow prior to therapy:
    • Tube fed group: Normal = 8; abnormal = 10 (44% normal)
    • Oral group: Normal = 10; abnormal = 3 (76% normal)
  • Karnofsky score prior to therapy:
    • Tube fed group: 80 (50-90)
    • Oral group: 70 (60-90)


  • Mean weight at start of therapy (% usual body weight):
    • Tube fed group: 80% (74-104%)
    • Oral group: 85% (81-100%)


  • Memorial Sloan-Kettering Cancer Center, New York


Summary of Results:

1.  Mean body weight change prior to randomization per pt interview 

Stratification (for both groups)

Number of patients

Weight loss (Percent usual weight)

Statistical Significance of Group Difference

Cancer site:


All others





-2.6 + 2.7

-9.8 + 8.1



p = 0.008

Feeding group:







- 7.9 + 7.7

- 6.6 + 7.6




2.  Mean body weight change at end of radiation therapy

Stratification (for both groups)

Number of patients

Weight loss (Percent initial weight at start of radiation therapy)

Statistical Significance of Difference between tube fed and oral groups*

Tube fed group:


All others





-3.8 + 3.4

0.2 + 5.9



p = 0.005

Oral group:


All others





-3.3 + 1.5

-7.3 + 4.2



p = 0.005

*There was no significant difference between tube and oral fed groups with nasopharyngeal carcinoma; however, tube fed patients with all other head and neck cancers had significantly less weight loss

3.  Other findings:


Mean duration of maximum toxicity (weeks)*

Caloric intake during radiation therapy (kcal/kg)**

Protein intake during radiation therapy (g/kg)**

Serum albumin (decrease during treatment in g/dl)***

Tube fed

3.1 + 1.3




2.4 + 1.0




*Earlier and greater toxicity in tube fed group may have been due to greater number of stage IV cancers, and wider radiation field, in this group

**Tube-fed group maintained goal caloric/protein intake during period of maximum toxicity, while oral group's calorie/protein intake dropped during this period

***NS; at one year post-treatment, patients had still not regained pre-treatment serum albumin levels

Author Conclusion:

The authors concluded that improved body weights in tube-fed head and neck cancer patients, despite similar treatment toxicities when compared to an orally fed group, demonstrate that tube feeding provides better outcomes during radiation therapy for head and neck cancer than oral feeding alone.

The authors suggested that the goal caloric intake of 40 kcal/kg may be adequate to prevent weight loss, but seems inadequate to promote weight gain in this patient population.  In addition, the researchers mentioned that the patients' failure to return to pre-treatment serum albumin may indicate aberrations in protein metabolism caused by either cancer or by radiation therapy.  The researchers suggested further study to define metabolic requirements of head and neck cancer patients receiving radiation therapy.

Funding Source:
Government: National Cancer Institute
University/Hospital: Memorial Sloan-Kettering Cancer Center
Reviewer Comments:
  • Older study; research methods and standards may not be as rigorous compared with current standards
  • Older study; nutrition assessment, tube feeding, and radiation therapy modalities may be different from current methods
  • Initial body weights reported per patient interview
  • Specific tube feeding formula was not mentioned; tube feeding formula was changed during the study period for 6 patients
  • Toxicity scale compiled by study personnel; does not appear to have been validated
  • Methods of statistical analysis, as well as level of statistical significance, not discussed
  • Performance status was not evaluated in results section
  • Some patients received chemotherapy in addition to radiation therapy; difficult to separate out effects of radiation therapy in these patients
  • Although groups were randomized, 76% of oral group had normal swallowing ability vs 44% tube fed 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? ???
  2.2. Were criteria applied equally to all study groups? ???
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
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.) 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? 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? 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? ???
  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? ???
  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? ???
  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? 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)? No
  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? ???
  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? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???