EAL

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

Citation:

Alexandre J, Gross-Goupil M, Falissard B, Nguyen ML, Gornet JM, Misset JL, Goldwasser F. Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy. Ann Oncol. 2003; 14: 36-41.

PubMed ID: 12488290

Study Design:

Case Control Study

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To assess the influence of nutritional and inflammatory status of cancer patients on chemotherapy tolerability.

Inclusion Criteria:

Treated at the oncology department of Paul Brousse Hospital (Villejuif, France) by four medical oncologists
Treated with conventional chemotherapy regimens containing already approved cytotoxic agents
Written, informed consent to a computerized collection of their clinical data.

Exclusion Criteria:

Human immunodeficiency virus infection
Previous treatment with high-dose chemotherapy, stem cells or bone marrow support
Suspected or documented bone marrow involvement, or concomitant radiotherapy.

Description of Study Protocol:

Recruitment

High-risk patients were identified from a cohort of more than 100 consecutive patients being treated by the department of oncology at the Paul Brousse Hospital in Villejuif, France between January 1999 and January 2000.

Design

Part one: Patients in study group A were compared to group B
- Study group A consisted of 48 consecutive cancer patients who had experienced severe hematological toxicity (SHT) after the first cycle of newly prescribed chemotherapy regimen
- Study group B consisted of 58 patients that were randomly chosen from 110 similar patients treated with chemotherapy but who did not experience severe toxicity; the 58 patients were determined for a 95% CI 10% or more for a specificity about 80%.
Part two: A subset (N=37) of patients who received a monochemotherapy (topotecan) was analyzed separately.

Intervention

Initiation of new chemotherapy regimen.

Statistical Analysis

Quantitative variables were graphed to assess for normality and logarithmically transformed if distribution found to be skewed
T-tests were used to compare quantitative (continuous) variables
Chi-square tests were used to compare qualitative variables
A receiver operating characteristic (ROC) curve was determined for NIS with cut-off as the value corresponding to the inflexion point of the curve
For the variable clinical PS, two cut-off points (one or more and two for more) were used
No intent-to-treat analysis.

Data Collection Summary:

Timing of Measurements

The following characteristics were taken at baseline, before first chemotherapy cycle:
- Demographics
- Tumor/cancer type
- Chemotherapy history
- Bilirubin, hemoglobin, platelet count
- Current chemotherapy regimen
- Renal function (evaluated from creatininemia, body weight, sex and age using the Cockcroft and Gault to calculate creatinine clearance)
- Nutritional status (evaluated by albumin and pre-albumin)
- Clinical performance status (PS)
- Acute phase proteins, C-reactive protein (CRP) and alpha-1 acid glycoprotein (AAG)
- Nutritional and inflammatory status (NIS), calculated as a ratio [(CRP x AAG)/(albumin x pre-albumin)].
SHT was assessed after first cycle of the new chemotherapy regimen and was defined as either neutropenic fever (neutrophils less than 1,000 per mm³ and fever of 38.5 degrees C or more) or severe thrombocytopenia (platelets nadir of less than 25,000 per mm³).

Dependent Variables

Presence or absence of severe hematological toxicity (SHT).

Independent Variables

Nutritional and inflammatory status (NIS).

Description of Actual Data Sample:

Initial N: 107 (37% male)
Attrition (final N): 107 (48 consecutive cancer patients who experienced SHT after the first cycle of a new chemotherapy regimen and who met inclusion criteria; 59 patients who did not experience SHT, control)
Age: Median of 56 years (range 33 to 75 years).

Other Relevant Demographics

Cancer type:
- Breast or gynecological cancers (38%)
- Gastrointestinal neoplasia (27%)
- Lung cancer (15%)
- Other carcinomas (11%)
- Sarcomas (9%).
Among those who experienced SHT, 85.4% and 61.4% experienced neutropenic fever and severe thrombocytopenia, respectively
Significant differences in baseline characteristics between groups:
- Hemoglobin was lower in patients experiencing SHT (10.7 in group A vs. 11.5g per dL in group B; P=0.02)
- Group A had worse clinical PS before first chemotherapy cycle (P<0.001)
- NIS was significantly higher for patients experiencing SHT (group A) (P<0.0001), which takes into account nutritional status and acute phase protein responses:
  - Serum albumin and pre-albumin were significantly decreased in group A patients (P<0.0001)
  - CRP and AAG were significantly elevated at baseline in group A patients (P<0.001 and P<0.0001, respectively)
- PS and NIS remained significantly higher in group A patients when those receiving more than two drugs were excluded from analysis (P<0.0001).

Location

Paris, France.

Summary of Results:

Key Findings

Among those who experienced SHT, 85.4% and 61.4% experienced neutropenic fever and severe thrombocytopenia, respectively
Compared to those without SHT, patient who experienced SHT were found to have the following baseline characteristics:
- Lower hemoglobin (10.7 in group A vs. 11.5g per dL in group B; P=0.02) at baseline
- Worse clinical PS before first chemotherapy cycle (P<0.001)
- Higher NIS (P<0.0001), which takes into account the following nutritional status and acute phase protein responses:
  - Serum albumin and pre-albumin were significantly decreased in group A patients (P<0.0001)
  - CRP and AAG were significantly elevated at baseline in group A patients (P<0.001 and P<0.0001, respectively).
Using a cut-off for zero or one for PS, sensitivity was 98% and 43%, with specificity at 38% and 90%, respectively
Using a cut-off for one for NIS, sensitivity was 89% and specificity was 66%
Amongst patients treated with a single agent (topotecan), determinants for SHT were PS (P<0.0001) and NIS (P<0.0001).

Author Conclusion:

Altered nutritional and inflammatory status correlates with increased risk of severe hematological toxicity following anti-cancer treatment. Thus, encouraging use of NIS as a practical and reliable parameter to prospectively identify patients at risk of toxicity prior to initiation of a new chemotherapy regimen.

Funding Source:

University/Hospital:

Groupe Hospitalier Cochin, Hopital St Louis and Hopital Paul Brousse, Paris, France

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?	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?	No
	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?	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%.)	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?	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?	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?	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?	Yes
	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?	No
	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?	???
	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)?	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?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes