EAL

ONC: Radiation Therapy (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare intensive nasogastric tube feeding with optimal oral nutrition during radiation therapy in patients with advanced head and neck cancer in order to evaluate the effects of nutritional support on tumor treatment efficacy, tumor recurrence and patient survival.

Inclusion Criteria:

Measurable, locally advanced, inoperable squamous carcinoma of the oral cavity, oropharynx, larynx or hypopharynx.
Primary and recurrent nasopharyngeal cancer.

Exclusion Criteria:

Early stage cancer of the glottic larynx treated solely by radiation therapy with a high likelihood for cure and minimal nutritional deficits.
Patients unable to ingest food orally.

Description of Study Protocol:

Recruitment : 40 patients randomized. Recruitment procedures not specified.

Design: Prospective, Randomized intervention trial

Blinding used (if applicable): N/A

Intervention (if applicable):

1. ORAL Nutrition Group: (Oral Group)

Initial intake goal: 40 kcal/kg/day; 1-1.5 g pro/kg/day
Nutrition assessment and diet counseling to achieve intake goals; individualized diet pattern given based on weight, height, age, sex, and degree of previous weight loss. Ideas and recipes given to increase caloric density.
Oral nutrition supplement provided as indicated to achieve kcal goals
Other aids provided as required (artificial saliva, antiemetics)

2. NASOGASTRIC Nutrition Group (NG group)

Upon tube placement, patients were instructed in proper techniques of tube feeding, preparation of formula, rates of administration, care of the tube (either polyurethane or Silastic feeding tubes), measures for sanitation, and care of equipment. Instructional books for home reference provided.
Received an individually defined liquid formula based on body weight, height, age, sex, and degree of previous weight loss.
Initial intake goal: 40 kcal/kg/day; 1-1.5 g pro/kg/day. IF no wt. gain: kcal intake increased by 5 kcal/kg/day.
Began on isotonic formula; if higher kcal and pro intakes required, given high caloric-density formula (Isocal HCN 2 kcal/ml).
Patients' families were active participants.

Statistical Analysis : Procedures not specified. Comparisons of means or medians in results.

Data Collection Summary:

Timing of Measurements:

Dietary intake, body weight, and toxicity to therapy: Baseline, weekly for 8 weeks

Serum protein and anthropometrics: At entry, week 4, week 8 and 1 month after radiation therapy ended.

Tumor status: At conclusion of radiation therapy and during routine follow-up (9-39 mos)

Dependent Variables

Dietary intake: diet history and 24 hour recall (baseline), and weekly 3 day food records
Serum albumin
Anthropometric measurements: height, weight, mid-arm circumference (Durnin) (study-defined scale and Lange calipers)
Performance status: Karnofsky scale (0-100)
Treatment toxicities: Patient interviews by R.D. Assessed on 0-4 scale; 0=no toxicity, 4=life threatening. Grades defined by clinical symptoms: dysphagia, xerostomia, mucositis, nausea, vomiting, constipation, and diarrhea; taste changes (normal, partial, complete loss)
Tumor status

Independent Variables Nutrition support: (oral vs. nasogastric)

Control Variables: None specified.

Description of Actual Data Sample:

Initial N: 40 (22 NG: 18 M, 4 F; 18 Oral: 14 M, 4 F)

Attrition (final N): 35 evaluable (18 NG; 17 Oral) gender not specified

Age: NG: 53+15 years; Oral: 55+13 years

Ethnicity: Not given

Other relevant demographics: N/A

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

Mean initial body weight loss on entry - wt. before onsest of symptoms 6 & 12 mos before therapy (%+SD): NG: 7.7+7.1; Oral: 6.6+7.7

Significance of differences (or not) not indicated.

Location: New York, New York

Summary of Results:

Dietary Intake:

NG Group Oral Group Significance

Mean (range) Mean (range)

Kcal intake

(kcal/kg/day) 39 (33-42) 30 (28-32) p<.001

Pro. intake

(g/kg/day) 1.4 (1.2-1.5) 1.1 (0.6-1.3) p<.01

Ser albumin:

Median baseline differences n.s;
At week 4: significant decreases (p<.01) in both groups
NG group tended to recover pretreatment median serum albumin levels sooner at end of radiation therapy and 2 months after therapy.

Weight loss:

No difference in mean body weight loss between NG (3.5% loss) and Oral (5% loss) group for pts. w/nasopharyngeal ca.

Pts. w/ oropharyngeal, hypopharyngeal, laryngeal, and recurrent nasopharyngeal ca, and ca of oral cavity had less body wt. loss w/NG (0.6% loss) compared w/ oral (6.1% loss), p,.04.

Mid-arm muscle circumference (MAMC):

Median MAMC (n=24) n.s.
NG group tended to maintain median MAMC throught radiation therapy
Oral group had a significant decrease in median MAMC during radiation therapy (p<.01).

Toxicities

Both groups initiated severe toxicities (grade 3) during second week of radiation therapy
Duration of severe toxicity (grade 3) was greater for tube fed group (mean 3.3 weeks) than for Oral group (mean 1.8 weeks), p,.02.

Tumor response

No difference in partial tumor response rate compared with complete tumor response rate (NG: 16/18; vs Oral: 14/17), n.s.

Slightly longer duration of response in those who had recurrence compared with those without recurrence (NG: 4.5 mos vs. Oral:3.4 mos), n.s.

Survival

No difference in patient survival patterns between NG and Oral groups

Quality of Life

Karnofsky scale measures showed no difference in performance status between the two nutrition groups.

Other Findings:

Median field size and median cumulative radiation dosage to primary tumor sites :

Slight larger field size in NG than Oral (n.s.)

Total radiation dosage to primary site: n.s.

Author Conclusion:

Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy was unchanged. It is still possible that a higher caloric and protein intake maintained throughout a longer period of active treatment with radition therapy may demonstrate a therapeutic benefit of nutritional intervention, and may allow simultaneous use of chemotherapy and escalation of radiation therapy, which may ultimatley lead to better results.

Funding Source:

Government:	NIH
University/Hospital:	Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York University Nedical Center

Reviewer Comments:

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?	???
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)	Yes
	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.)	Yes
	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?	???
	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?	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?	Yes
	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?	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?		???
	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)?	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?	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?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes