EAL

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

Citation:

Phippen NT, Lowery WJ, Barnett JC, Hall LA, Landt C, Leath CA 3rd. Evaluation of the Patient-Generated Subjective Global Assessment (PG-SGA) as a predictor of febrile neutropenia in gynecologic cancer patients receiving combination chemotherapy: A pilot study. Gynecol Oncol. 2011; 123(2): 360-364.

PubMed ID: 21864889

Study Design:

Diagnostic, Validity or Reliability Study

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To evaluate the reliability of a pre-chemotherapy Patient-Generated Subjective Global Assessment (PG-SGA) score as a predictor of febrile neutropenia (FN) in gynecologic cancer patients receiving primary combination chemotherapy.

Inclusion Criteria:

Gynecologic oncology patients treated with primary combination chemotherapy at the study institution from 2005 to 2009
Patients with either fallopian tube or primary peritoneal carcinoma were included with those having an ovarian cancer diagnosis
Patients with complete data available for analysis (considered complete when pre-chemotherapy PG-SGA score, pre-chemotherapy serum albumin, surveillance complete blood count testing, and neutropenia/FN diagnostic criteria were available).

Exclusion Criteria:

Receipt of single agent chemotherapy
Previous treatment with chemotherapy
Prior radiation therapy
Use of prophylactic hematopoietic colony stimulating factors (CSF) prior to first chemotherapy cycle
Prophylactic receipt of CSF during the study period (whereas patients receiving CSF therapy in response to grade three or four neutropenia or FN at the discretion of their provider remained in the study and were included in the final statistical analysis).

Description of Study Protocol:

Recruitment

Following IRB approval, a retrospective review at the study institution identified patients that met the inclusion criteria.

Design

Diagnostic, validity or reliability study.

Intervention

Clinicopathologic variables, pre-treatment laboratory values and PG-SGA were obtained from medical records for eligible patients. Patients were divided into three groups based on neutropenia during chemotherapy per CTC 3.0 toxicity guidelines:
- No grade three or four neutropenia
- Grade three or four neutropenia
- FN
Data were then used in statistical analysis.

Statistical Analysis

Median baseline PG-SGA scores, serum albumin levels and hemoglobin levels were calculated for each group and compared using Kruskal-Wallis one-way ANOVA. Statistical significance was set at 0.05.
A receiver operator curve (ROC) was created for PG-SGA scores in order to evaluate the diagnostic value for predicting FN. The area under the ROC curve (AUC) was used as an index of accuracy.

Data Collection Summary:

Timing of Measurements

Pre-chemotherapy nutritional and hematologic parameters, and PG-SGA scores were used in the statistical analysis.

Dependent Variables

For comparison of baseline parameters:
- Albumin
- Hemoglobin
- Body mass index (BMI)
For evaluation of the diagnostic value of PG-SGA: Neutropenia (divided into three groups).

Independent Variables

PG-SGA scores (Scores from the patient-completed section and the clinician-related sections are summed; an increasing score is predictive of malnutrition).

Control Variables

Age
Race
Tumor distribution
Cancer stage
Chemotherapy regimen.

Description of Actual Data Sample:

Initial N

58 females [76 patients met initial eligibility criteria but only 58 (76%) with complete data available for analysis]:

Group 1: N=25
Group 2: N=28
Group 3: N=5

Attrition (final N)

58 females.

Age

Mean age, 60.8 years.

Ethnicity

Majority white [43 of 58 patient (74%)].

Other relevant demographics:

Majority 42 (72.4%) were being treated for epithelial ovarian cancer (EOC) and 16 (27.6%) were being treated for uterine cancer (UC)
26 of the 42 (62%) patients with ovarian cancer were diagnosed with advanced stage disease
Uterine papillary serous carcinoma was the most common diagnosis among UC patients (38%)
Carboplatin and paclitaxel was the most common combination chemotherapy regimen received for 52 of 58 patients (91%).

Location

Ft. Sam Houston, Texas.

Summary of Results:

Key Findings

Five of the 58 (8.6%) study patients were diagnosed with FN
Median baseline PG-SGA scores, serum albumin and hemoglobin varied for all groups of patients, with the greatest differences seen between Group One (no grade three or four neutropenia) and Group Three (FN)
Median BMI of Groups Two and Three not significantly lower than that of Group One.


	Group One	Group Two	Group Three	P-value
	(N=25)	(N=28)	(N=5)
PG-SGA	6	7	14	0.019
Albumin	4.2g per dL	4.0g per dL	3.4g per dL	0.041
BMI	30	26	26	0.296
Hemoglobin	12.1g per dL	11.75g per dL	10.6g per dL	0.05

A receiver operator curve (ROC) was plotted based on the ability of the PG-SGA to predict FN. The overall AUC of the ROC curve was 0.831±0.064 (0.706 to 0.956, 95% CI, P=0.015)
Using the ROC, selecting a PG-SGA score of 7.5 to be predictive of FN yields a sensitivity of 100% and a specificity of 60%. Selecting a PG-SGA cutoff value of 12.5 improves the specificity to 81% while decreasing sensitivity to 80%.

Author Conclusion:

PG-SGA scores were higher for patients experiencing FN and may be a reasonably predictive marker of FN in patients receiving multi-agent primary chemotherapy and likely benefactors of prophylactic CSF
The PG-SGA appears reliable because the score is a composite of several variables, some of which have been noted as independent risk factors of FN or chemotherapy induced neutropenia in other studies.
A prospective evaluation of the scored PG-SGA correlating with febrile neutropenia utilizing a single institutional trained scorer for the PG-SGA to improve data precision could be incorporated into a prospective chemotherapy trial
It remains possible that future studies will support PG-SGA being routinely used to identify patients most at risk of severe hematologic toxicity in order to allow primary CSF prophylaxis, which can be tailored, and successful completion of chemotherapy regimens can increase.

Funding Source:

Government:

Funding source is unclear, but appears to be associated with the U.S. military

Reviewer Comments:

No clear if data collectors were blinded, but assumed study findings not affected due to retrospective data collection and many outcomes measured using objective tests
Strengths of the study:
- Significant association between the scored PG-SGA and patients at risk of developing FN
- Narrow focus of patient population (could also be a weakness)
- Ease of reproducibility and validation given the wide availability and the nominal costs of PG-SGA data
Weaknesses of the study:
- Incomplete data inherent in retrospective studies (only 76% of patients treated)
- Inter-grader variability scoring of the PG-SGA since the physical exam was completed by different staff members
No sure how the PG-SGA cutoff values reported in the Results section were selected. It might have been helpful if more information was provided on the sensitivity and specificity for a range of different cutoff values, since the diagnostic test is based on a continuous measurement
Although the ROC analysis sheds some light on the predictive power of PG-SGA scores, it would have been helpful if it was compared with another test, such as the purely objective nutritional inflammatory status (NIS) ratio mentioned in Discussion.

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?		No
	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?	No
	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")?	No
4.	Was method of handling withdrawals described?		N/A
	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%.)	N/A
	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.)	???
	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?	No
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?	N/A
	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?	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?	Yes
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?	N/A
	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?	N/A
	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)?	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes