High C-reactive protein/albumin ratio predicts unfavorable distant metastasis-free survival in nasopharyngeal carcinoma: a propensity score-matched analysis

Abstract

Background: Recent studies have indicated that the C-reactive protein/albumin (CRP/ALB) ratio (CAR) may represent a simple inflammation-based index for assessing the host inflammatory response. In this study, the prognostic value of the CAR for distant metastasis-free survival (DMFS) in nasopharyngeal carcinoma (NPC) was assessed.

Methods: A total of 1,168 non-metastatic NPC patients from Sun Yat-sen University Cancer Center were retrospectively included. The optimal cutoff value for CAR was defined by the Cutoff Finder online tool. Propensity case-matched analysis was performed to adjust for potential differences in baseline characteristics. Subsequently, the prognostic value of the CAR for DMFS was validated in a 756 validation cohort with NPC.

Results: The optimal CAR cutoff value was 0.081. Patients with high CAR values had significantly poorer DMFS than those with low CAR in univariate and multivariate analyses before propensity score matching. The CAR could also significantly stratify patients into different risks of developing distant metastasis in subgroup analysis. Propensity score analyses showed that CAR remained a prognostic factor for DMFS, thus excluding other interpretations and selection bias. Moreover, the prognostic value of the CAR was robustly confirmed in the external validation cohort.

Conclusion: CAR is an inexpensive and easy-to-measure inflammatory index that may aid clinicians in the development of individualized treatment and follow-up strategies for patients with non-metastatic NPC.

Keywords: C-reactive protein; albumin; metastasis; nasopharyngeal carcinoma; prognosis; propensity score.

Figure 1

Hazard ratios (HRs) for distant metastasis-free survival (DMFS) for various cutoff points of the C-reactive protein/albumin (CRP/ALB) ratio (CAR) in patients with nasopharyngeal carcinoma. Notes: The value of X-axis represented all the possible values of CAR in our patient population. The Y-axis represents HRs. From the left to right of the X-axis, all the possible CAR values were tested as a cutoff for discrimination of DMFS and the corresponding HR and its 95% confidence interval (CI) were calculated and plotted (two dashed lines represent upper and lower limits of 95% CIs, respectively, and the solid line between the two dashed lines represents HR). The vertical line designates the optimal cutoff point with the most significant split (log-rank test). The plots were generated using Cutoff Finder.

Figure 2

Prognostic value of the C-reactive protein/albumin ratio (CAR) for distant metastasis-free survival (DMFS) in the training cohort before matching (A), the validation cohort (B) and training cohort after 1:1 ratio matching (C).

Figure 3

Forest plot of subgroup analysis showing hazard ratios (HRs) and 95% CI (bars) for DMFS in 1,168 patients with nasopharyngeal carcinoma who underwent definitive radiotherapy. Note: Subgroups were defined by factors showing significant associations with the C-reactive protein/albumin ratio (CAR) and DMFS. Abbreviations: 3DCRT, three-dimensional conformal radiation therapy; ALB, albumin; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CAR, CRP/ALB ratio; CI, confidence interval; CRP, C-reactive protein; CRT, conventional radiotherapy; chemo-radiotherapy, chemotherapy plus radiotherapy; DMFS, distant metastasis-free survival; EBV-DNA, Epstein–Barr virus DNA; GLB, globulin; HGB, hemoglobin; IMRT, intensity-modulated radiation therapy; LDH, lactate dehydrogenase; RT, radiotherapy; WBC, white blood cell.