EAL

ONC: Nutrition Status and Outcomes in Adult Oncology Patients (2013)

Citation:

Robinson DW Jr, Eisenberg DF, Cella D, Zhao N, de Boer C, DeWitte M. The prognostic significance of patient-reported outcomes in pancreatic cancer cachexia. J Support Oncol. 2008; 6(6): 283-290.

PubMed ID: 18724539

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To explore the relationship between patient-reported outcomes (PROs) and survival in pancreatic cancer patients with involuntary, significant weight loss (cachexia).

Inclusion Criteria:

Men and women with newly diagnosed stage II to IV pancreatic cancer were enrolled if they lost 10% or more of their pre-study weight or if they lost 5% or more of their weight within 90 days before randomization
Life expectancy of at least three months
Karnofsky performance status (KPS) score of 70 to 100
Eligibility to receive gemcitabine chemotherapy
Patients were stratified according to documented weight loss over the preceding 30 days (5% or less vs. more than 5%) and tumor stage (II/III vs. IV).

Exclusion Criteria:

Not described.

Description of Study Protocol:

Recruitment

Patients who reported outcomes (PROs) were randomized from 23 international centers.

Design

Randomized double-blind placebo-controlled phase II trial.

Blinding used

Double bilind trial (investigators nor subjects knew what treatment was provided and taken).

Intervention

Infliximab (Remicade 3mg or 5mg per kg), or placebo all in combination with gemcitabine (Gemzar).

Statistical Analysis

PRO scores and clinical data were considered to be continuous variables and were reported with standard summary statistics
Hazard ratios were evaluated using high and low categories for each PRO based upon the median baseline score except for the FACIT-F, in which a threshold of 30 was used based on expert recommendation
For hemoglobin findings, survival results were adjusted for age, gender and KPS
Spearman correlation was used to explore the associations across measures with non-parametric data
Pearson's correlation was applied when the data was non-parametric
No adjustments for multiple testing of statistical significance were made
The SAS system (version 8.2 SAS) was used for all study analyses.

Data Collection Summary:

Timing of Measurements

Validated patient-health questionnaires were selected for this study such as the fatigue and nutritional health assessment (FACIT-F score range zero to 52)
The Functional Assessment of Anorexia/Cachexia Therapy questionnaire (FAACT, score range zero to 48) was used to determine whether or not patients had a good appetite over the past seven days
Patient pain levels were assessed with the worst pain evaluation of the Brief Pain Inventory (BPI) in which scores ranged from zero to 10; higher scores reflected greater pain
The short form 36 general health survey (SF-36) also was used to capture multiple aspects or domains of patient health. The domains covered in the survey were general health, physical role, emotional role, physical functioning, mental functioning, social functioning, bodily pain and vitality.
Two summary scales such as the physical component summary (PCS) and the mental-component summary (MCS) was also constructed from the domains of the short form general health survey.

Dependent Variables

Patient reported outcomes (PROs) and survival: PRO information was gathered upon patient presentation to the clinic before any treatment procedures began. Treatment-site coordinators were provided with instructions for administering the PRO and trained about the importance of these data to the study sponsor.

Description of Actual Data Sample:

Initial N: 89 men and women
Attrition (final N): 86 men and women (54% males, 46% females)
Age: Mean age of 64.8 years
Ethnicity: 99% Caucasian
Anthropometrics: At baseline, the population had a mean weight of 65.5kg and a BMI of 22.9kg/m².

Summary of Results:

Key Findings

Patients who lost 5% or less of their weight within 30 days of treatment had a median overall survival of 7.3 months (95% CI: 6.3 to 9.1), whereas those who lost over 5% of their weight survived for a median of 6.5 months (95% CI: 4.6 to 10.7, log rank P=0.44)
At baseline, the mean FACIT-F score for all patients was 31.9 and the FAACT nutritional health score was 28.2
The baseline mean worst pain score was 3.5 representing a mild to moderate pain with 23% of patients using either strong or weak opiods
Patients reported impaired health across all SF-36 measures at baseline with the lowest mean scores being in physical role (32.1), PCS (36.2), physical functioning (37.9) and pain 37.8
Overall, correlations between clinical and PRO measures were in the weak to moderate range (R=0.25 to 0.48)
A high FACIT-F score (higher than 30) indicated low fatigue was the best predictor of longer overall survival in a stepwise Cox proportional hazards model (HR, 0.47; CI: 0.3 to 0.74)
The median overall survival was 9.1 months (CI: 7.2 to 11.4) for patients having low fatigue indicated by higher scores higher than 30, N=48 and 5.2 months (CI: 4.0 to 7.2) for those with high fatigue (indicated by low score 30 or less; N=32; log rank P=0.002).

Author Conclusion:

The findings from this study support several features of an a priori clinical benefit model. Patient reported fatigue provided powerful prognostic information and tracking of this symptom may be useful for treatment planning and medical monitoring of advanced stage pancreatic cancer patients with cachexia. The results need to be confirmed by larger trials.

Funding Source:

Other:

Centocor Inc., a division of Johnson & Johnson Pharmaceutical Services

Reviewer Comments:

Several limitations to this study were noted. First, the sample size was small and this was due to the difficult population to explore cancer cachexia therapy. Second, problems with missing data arose from patients discontinuation and death. Finally, survival analysis may have been influenced by a synergistic effect between the standard treatment, gemcitabine and infliximab.

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?	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?		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?	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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?		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?	Yes
	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?		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)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes