Table 4 Results of the flexible spline-based model (N=269)

Variables	HR (95% CI) ^a	P -value for test of no association
Stage: (IIIB+pleural effusion/4 vs IIIA/IIIB)	1.859 (1.284, 2.691)	<0.001
ECOG^b performance status: (2 vs 0–1)	1.336 (0.923, 1.935)	0.116
Smoking status: (ever vs never)	2.248 (1.419, 3.561)	<0.001
Chemotherapy type: (single vs double)	1.462 (0.990, 2.160)	0.041
Log₂ CRP: (per doubling of CRP values)	^*	0.003 (overall P-value)^#
Albumin: (per ↓^c of 1 g l^–1)	^**	0.001 (overall P-value)^#
Log₂ LDH: (per doubling of LDH values)	2.281 (1.661, 3.142)	<0.001
Alkaline phosphatase: (per ↑of 10 U l^–1)	1.012 (0.980, 1.041)	0.366
Neutrophil counts: (per ↑^d of 1 × 10⁹ l^–1)	1.072 (1.025, 1.122)	0.001
Lymphocytes: (per ↓ of 1 × 10⁹ l^–1)	1.313 (1.035, 1.666)	0.012
Deviance^e	1873.3
AIC	1909.3

Abbreviations: AIC=Akaike's information criterion; CRP=C-reactive protein; LDH=lactate dehydrogenase.
^aAdjusted hazard ratio (HR) and 95% confidence interval (95% CI).
^bEastern cooperative oncology group.
^c↓: decrease.
^d↑: increase.
^eDeviance=−2^*log-likelihood.
^*Both the time-dependent (P=0.033) and non-linear (P=0.015) effects were significant. The estimated non-linear effects, at selected follow-up times, are shown in Figure 2.
^**Both the time-dependent (P=0.0001) and non-linear (P=0.038) effects were significant. The estimated non-linear effects, at selected follow-up times, are shown in Figure 3.
^#P-value for a likelihood ratio test, with 5 degrees of freedom, of the null hypothesis of no association, obtained by comparing the deviances of (i) a flexible model where both time-dependent and non-linear effects of a given variable are modeled by splines, vs (ii) a simpler ‘reduced’ model, which does not include the variable being tested (see the section on “Statistical analyses” for details of the test).

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