Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

Abstract

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 ¼ 1.11 per each doubling of CRP value, 95% CI: 1.03 -1.20, P ¼ 0.008). However, both the PH assumption (P ¼ 0.033) and the linearity assumption (P ¼ 0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. CONCLUSION: 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.

Lung cancer histologies associated with emphysema on computed tomography

“…Patient information is obtained from systematic chart review, tumour board meetings, and patient interviews by specialized oncology data managers. This database has been used previously for research purposes [13][14][15][16].…”

Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

“…For example, systemic inflammatory reaction indicators, such as elevation of serum C-reactive protein (CRP) and reduction in serum albumin, are reported as prognostic factors independent of stage in various solid cancers, including unresectable NSCLC (5)(6)(7)(8)(9). The Glasgow Prognostic Score (GPS), which is based on both albumin and CRP (10)(11)(12), is also a prognostic factor that is more effective than PS, even if treatment has been provided for unresectable NSCLC (10,11,13).…”

Elevated Serum C-Reactive Protein as a Prognostic Marker in Small Cell Lung Cancer

“…Third, cancer cells could increase the production of inflammatory cytokines, which could induce high CRP concentration in cancer patients 4. Many studies showed the elevation of pretreatment CRP to be a significant prognostic parameter in patients with esophageal cancer, 8-10 hepatocellular carcinoma,11 colorectal cancer,12-14 renal cell cancer,15-17 ovarian cancer,18 and non-small cell lung cancer (NSCLC) 19-23. Furthermore, we recently reported an association between preoperative serum CRP levels and pathologic parameter such as tumor size and lymphovascular invasion in patients with NSCLC 24…”