EAL

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

Citation:

Ross PJ, Norton A, Priest K, Waters JS, Eisen T, Smith IE, O'Brien MER. Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? British Journal of Cancer. 2004; 90: 1,905-1,911.

PubMed ID: 15138470

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 assess whether weight loss at presentation had an influence on the toxicity patients suffered during chemotherapy and on whether weight loss altered the amount of chemotherapy delivered
To assess whether stabilization of weight during treatment had any effect on outcome.

Inclusion Criteria:

Patient with small cell lung cancer (SCLC), stage III or IV non-small-cell lung cancer (NSCLC) or mesothelioma
Patient treated with chemotherapy
Data recorded on RMH lung unit research database between 1994 and March 2001.

Exclusion Criteria:

Unknown weight loss status at presentation
Patient did not receive a standard chemotherapy regimen within two months of presentation
Patient receiving prior radiotherapy and prior adjuvant or palliative chemotherapy.

Description of Study Protocol:

Recruitment

Lung Unit of the Royal Marsden Hospital.

Design

Study reviewed data that had been recorded prospectively on the RMH lung unit research database between 1994 and March 2001 for patients with SCLC, stage III or IV NSCLC or mesothelioma and treated with chemotherapy. Patients who stated they had lost weight at the time of presentation were compared to those who denied weight loss. Parameters measured included objective and symptomatic response, treatment-related toxicity and progression-free and overall survival. Within the group who had lost weight at presentation, those with continuing measured weight loss during chemotherapy were compared with those in whom weight stabilized or increased during the first 63 days of treatment.

Statistical Analysis

Response rates were compared between the patients with weight loss at presentation and those without by means of Fisher's exact test
Toxicity was graded zero to four and a comparison between groups was carried out by the means of Mann-Whitney test with trend
Comparison of the numbers of patients requiring cessation of treatment or a dose reduction because of toxicity was made by means of Fisher's exact test
Progression-free and overall survival from the date of first treatment and survival curves were generated by the method of Kaplan and Meier and compared by means of the log-rank test
Multi-variate Cox's proportional hazards model used to calculate relative risk of progression or death and to investigate the independent significance of prognostic variable.

Data Collection Summary:

Timing of Measurements

Weight loss assessed by direct questioning of patient during preliminary assessment by the doctor at first visit
Weight measured at each chemotherapy and outpatient clinic visit
Objective response to treatment classified using the WHO/UICC response criteria following serial CT scans every six weeks and chest x-rays every three weeks
Symptoms recorded at each attendance
Performance status recorded at baseline and at each attendance
Toxicity graded at each attendance,

Dependent Variables

Weight
Objective response to treatment classified using the WHO/UICC response criteria following serial CT scans and chest x-rays
Symptoms established by direct questioning and any change in symptoms compared to baseline was recorded; response to a symptom to treatment was defined as improvement in a particular symptom maintained for at least three weeks
Performance status
Toxicity graded according to WHO toxicity criteria by direct questioning, physical exam and measurement of full blood count, urea and electrolytes and liver function tests.

Independent Variables

Weight loss at presentation, prior to chemotherapy.

Control Variables

Chemotherapeutic regimen
Cancer diagnosis and stage
Gender
Age.

Description of Actual Data Sample:

Initial N

780 patients (496 males, 284 females).

Attrition (final N)

780 patients.

Age

Median age: 63 years (range 27 to 85 years)
SCLC: 65 (38 to 85) years
NSCLC: 62 (27 to 82) years
Mesothelioma 63 (42 to 77) years.

Other relevant demographics:

290 patients diagnosed with SCLC
418 patients diagnosed with NSCLC
72 patients diagnosed with mesothelioma.

Anthropometrics

No difference in incidence of weight loss among men (62%) compared to women (57%, P=0.02)
Patients reported weight loss more frequently with mesothelioma than with SCLC (P=0.01) or NSCLC (P=0.005).

Location

Royal Marsden Hospital, Great Britain.

Summary of Results:

Effects of Weight Loss at Presentation on Chemotherapy-related Toxicity

Fewer patients with weight loss (315 patients, 67%) completed three cycles of chemotherapy than those without weight loss (210, 81%, P<0.001)
- Difference confirmed in patients with NSCLC (64% vs. 78%; P=0.003) and was due to early disease progression
- Patient with SCLC had no significant difference in the numbers of patients completing at least three cycles of chemotherapy (77% vs. 84%; P=0.1)
Similar numbers of patients stopped treatment due to toxicity in both groups (P=0.7)
No significant differences in frequency of dose reductions (P=0.6) or treatment delays (P=0.2) according to weight change
Treatment delayed significantly more frequently in patients with weight loss associated with NSCLC than those without weight loss (9.0% vs. 4.0%; P=0.04)
NSCLC patients with weight loss were significantly more likely to develop severe anemia as toxicity than those without weight loss (P=0.0003)
Anemia was not more common in SCLC or mesothelioma patients with weight loss
No difference in other toxicities from chemotherapy were observed.

Effect of Weight Loss at Presentation on Objective and Symptomatic Response

No relationship between objective response and weight loss for patients with either SCLC (P=0.3) or NSCLC (P=0.05)
Lower response rate in patients with mesothelioma and weight loss (P=0.05)
NSCLC patients with weight loss had significantly more symptoms at presentation than those without weight loss (P<0.0001) and significantly fewer symptomatic responses (44% vs. 60%; P=0.004)
In patients with SCLC, there was neither a correlation between weight loss and number of symptoms (P=0.3) nor a statistically significant relationship with frequency of symptomatic response (52% vs. 64%; P=0.06)
Mesothelioma patients' number of symptoms was unrelated to weight loss (P=0.9) but patients with weight loss reported fewer symptomatic responses (33% vs. 65%; P=0.03).

Effect of Weight Loss at Presentation on Progression-free Survival

At time of analysis, disease progression was documented in 626 (80%) of the 780 patients in the study group; comprising 234 (82%) patients with SCLC, 336 (80%) patients with NSCLC and 56 (78%) patients with mesothelioma
Performance status and stage were most important prognostic factors for patients with both SCLC and NSCLC
Weight loss resulted in an increased RR of progression (1.4, 95% CI: 1.0 to 1.8) for patients with SCLC while weight loss was not a prognostic factor of progression-free survival for patients with NSCLC and no factors were significant predictors of progression-free survival in mesothelioma patients.

Effects of Weight Loss at Presentation on Survival

Overall survival was significantly shorter for patients with weight loss compared to those without weight loss with SCLC (six vs. 11 months; P=0.0003), NSCLC (six vs. nine months; P<0.0001) and mesothelioma (five vs. 12 months; P=0.025)
Multi-variate analysis demonstrated that performance status was prognostic for patients with SCLC (P<0.001), NSCLC (P<0.001) and mesothelioma (P=0.004)
Cancer stage was prognostic for patients with SCLC and NSCLC
Weight loss was prognostic factor for all cancers
Female gender predicts for improved overall survival (P=0.03) and progression-free survival (P=0.04) in patients with NSCLC.

Effect of Stabilization of Presentation Weight Loss on Progression-free and Overall Survival

For SCLC patients, weight stabilization did not significantly improve progression-free (P=0.8) or overall survival (P=0.95) in comparison to those who continued losing weight
Weight stabilization for patients with NSCLC resulted in significant improvement in both progression-free (increased from five to seven months, P=0.01) and overall survival (increased from seven to nine months; P=0.006)
Only three mesothelioma patients had weight stabilization during treatment and this did not affect survival.

Relationship Between Weight Loss and Response to Chemotherapy

	Objective Response Rate (%)			Symptom Response Rate (%)
	No Weight Lose	Weight Loss	P Value	No Weight Lose	Weight Loss	P value
SCLC	75%	69%	0.3	64%	52%	0.06
NSCLC	37%	34%	0.5	60%	44%	0.004
Mesothelioma	29%	9%	0.05	65%	33%	0.03

Progression-free and Overall Survival

	Progression-free Survival RR (95% CI)	Progression-free Survival P Value	Overall Survival RR (95% CI)	Overall Survival P Value
SCLC	No weight loss: 1.0 Weight loss: 1.4 (1.0 to 1.8)	0.02	No weight loss: 1.0 Weight loss: 1.4 (1.0 to 1.9)	0.003
NSCLC	No weight loss: 1.0 Weight loss: 1.0 (0.9 to 1.2)	0.0	No weight loss: 1.0 Weight loss: 1.3 (1.1 to 1.7)	0.009
Mesothelioma			No weight loss: 1.0 Weight loss: 1.9 (1.1 to 3.5)	0.03

Author Conclusion:

This study demonstrated that weight loss at presentation is an independent prognostic factor for survival of patients with NSCLC, SCLC, and mesothelioma. Weight loss also predicts toxicity from treatment.

Funding Source:

University/Hospital:

Royal Marsden Hospital

Reviewer Comments:

Data regardng nutrition interventions was not collected.

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%.)	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?		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.)	N/A
	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?	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?	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?	N/A
	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?	N/A
	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)?	N/A
	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?		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