EAL

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

Citation:

Hill A, Kiss N, Hodgson B, Crowe TC, Walsh AD. Associations between nutritional status, weight loss, radiotherapy treatment toxicity and treatment outcomes in gastrointestinal cancer patients. Clin Nutr. 2011; 30: 92-98.

PubMed ID: 20719409

Study Design:

Prospective Cohort Study

Class:

B - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To determine whether nutritional status at radiotherapy commencement or changes in nutritional status throughout radiotherapy were associated with treatment toxicity and outcomes in gastrointestinal (GI) cancer patients.

Inclusion Criteria:

Age 18 years or older
Primary diagnosis of GI cancer (including esophageal, gastric, pancreatic, gall bladder, liver, small bowel, colonic, rectal or anal tumors)

Had a body weight recorded at commencement and conclusion of radiotherapy
Attended Peter MacCallum Cancer Centre (PMCC) for curative external beam radiotherapy in Melbourne, Australia:
- Completed curative radiotherapy between November 2008 and March 2009 (retrospective chart audit)
- Underwent the first week of radiotherapy between March and June 2009 (prospective study).

Exclusion Criteria:

Age less than 18 years
Missing body weight documentation at commencement or conclusion of radiotherapy
Patients receiving radiotherapy for palliation.

Description of Study Protocol:

Recruitment

All subjects attended Peter MacCallum Cancer Centre (PMCC) for curative external beam radiotherapy in Melbourne, Australia.

Retrospective component: Those who completed curative radiotherapy between November 2008 and March 2009 and met all inclusion criteria were included in the retrospective chart audit.
Prospective component: Eligible patients were identified by screening all patients commencing radiotherapy between March and June 2009. Those who met all inclusion criteria and underwent the first week of radiotherapy during this time period were invited to participate.

Design

The study occurred at a specialist public hospital dedicated to cancer treatment, research and education, and involved both a retrospective audit and prospective study.

Statistical Analysis

No intent-to-treat analysis
Distribution of continuous variables were determined to be non-Gaussian using the Kolmogorov-Smirnov test
Mann-Whitney U-tests were used to compare weight change between groups
Kruskal-Wallis tests were used to detect differences in weight change according to ordinal outcome measure
Friedman tests were used to assess changes in toxicity prevalence and severity throughout radiotherapy
Spearman's rank correlation coefficients were used to examine associations between changes in weight, PG-SGA score and treatment toxicity
Fisher's Exact tests were used to compared nutritional classification against the presence or absence of treatment break, early treatment cessation and unplanned admission
Significance level set at P<0.05
Statistical Package for the Social Sciences (SPSS, version 17.0, IL, USA).

Data Collection Summary:

Timing of Measurements

Data collected included:

Age
Gender;
Primary diagnosis
TNM tumor stage (T, primary tumor size; N, regional lymph node involvement; M, distant metastases; number in each category indicates the degree of spread)
Radiation prescription
Chemotherapy protocol
Scored Patient-Generated Subjective Global Assessment (PG-SGA) (prospective study only)
Body weight, measured during week one and final week of treatment
Acute treatment toxicity was assessed and graded weekly by the treating radiation oncologist using the Upper or Lower GI Radiation Therapy Acute Toxicity Scoring tool
Treatment outcomes (completion of prescribed radiation and chemotherapy; occurrence of unscheduled breaks from radiotherapy treatment; unplanned admission to hospital).

Dependent Variables

Primary outcome: Acute radiotherapy treatment toxicity (including prevalence, severity and time of onset)
Secondary outcomes: Unplanned radiotherapy treatment breaks, completion of prescribed radiotherapy and chemotherapy and unplanned hospital admissions during radiotherapy.

Independent Variables

Nutritional status at commencement of radiotherapy
Changes in nutritional status throughout radiotherapy
Changes in body weight throughout radiotherapy.

Description of Actual Data Sample:

Initial N: 73 patients (64.4% male)
Attrition (final N): 73 patients (64.4% male)
Age: Median age 69 years (IQR, 61 to 77 years)

Anthropometrics

Median weight: 73.6kg (IQR,: 65.4 to 81.8kg)
23 patients with upper GI tumors; 50 patients with lower GI tumors
90% patients without metastases.

Location

Melbourne, Australia.

Summary of Results:

Key Findings

75% of patients lost weight throughout radiotherapy
Weight loss was greater among patients with unplanned breaks in radiotherapy compared to those without breaks in therapy (-3.1% vs. -1.6%, P<0.05)
Severity of radiotherapy toxicity was strongly correlated with PG-SGA score (ρ=0.839, P<0.001)
Toxicity severity was increased in those who experienced unplanned hospital admissions compared to those without admissions (42.1% vs. 9.3%, respectively, P<0.001).

Detailed Findings

Nutritional Status

Toxicity severity was strongly and positive association with change in PG-SGA score (ρ=0.839, P<0.001)
Those who did not complete chemotherapy experienced a greater change in PG-SGA score throughout radiotherapy than those who did not complete chemotherapy (median increase 17 vs. three, P<0.05).

Weight Loss

A total of 75% of patients lost weight throughout radiotherapy, with median weight change of -1.8% (IQR, -0.01 to -3.5%).
11% of patients lost over 5% of total body weight throughout treatment; 5.5% lost over 10% of total body weight throughout treatment
Patients with upper GI tumors lost more weight than those with lower GI tumors (median weight change -3.2% vs. -1.1%, respectively; P<0.01).

Treatment Toxicities

Toxicity severity increased significantly from week one to weeks four to six for the four most common toxicities: diarrhea, nausea, skin reactions and fatigue (P<0.05)
Nausea was significantly more severe by week two (P<0.05)
Diarrhea and skin reactions were significantly more severe by week three compared to week one (P<0.05).

Treatment Outcomes

A total of 16% of patients had unplanned breaks in radiotherapy, all of which experienced greater weight loss than those without treatment breaks (median change -3.1% vs. -1.6%, respectively; P<0.05)
Those with unplanned hospital admission(s) during radiotherapy experienced more severe toxicity that those who were not admitted (42.1% vs. 9.3%, respectively; P<0.001)
Admissions were related to management of severe toxicity (52.6%), nutrition support (21.1%), infection (15.8%) or other causes (10.5%)
Patients who did not complete prescribed chemotherapy (25.7%) experienced greater weight loss compared to those who completed therapy (median weight change -3.3% vs. -1.6%, respectively; P<0.05).

Author Conclusion:

Deterioration in nutritional status (as measured by weight loss) during radiotherapy may be associated with poorer short-term treatment outcomes in GI cancer patients. However, sample size was inadequate to determine effect of nutritional status on radiotherapy commencement or changes in nutritional status throughout radiotherapy (defined by PG-SGA) on treatment outcomes.

Funding Source:

University/Hospital:

Peter MacCallum Cancer Centre

Reviewer Comments:

Authors reported many non-significant trends, making it difficult to pull out significant outcomes.

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?	Yes
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.)	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?	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.)	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?		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.)	No
	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?	Yes
	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?	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?	No
	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)?	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?	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes