Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer.
BACKGROUND
C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption).


METHODS
We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC).


RESULTS
In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03-1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months.


CONCLUSIONS
Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP.
Department of Medicine and Oncology, McGill University, 687 Pine Avenue West, R4.29, Montreal, Quebec, H3A 1A1, Canada. bruno.gagnon@clinepi.mcgill.ca
B
B
Gagnon
M
M
Abrahamowicz
Y
Y
Xiao
M-E
ME
Beauchamp
N
N
MacDonald
G
G
Kasymjanova
H
H
Kreisman
D
D
Small
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D002097:C-Reactive Protein