Plasma IGFBP-2 levels after postoperative combined radiotherapy and chemotherapy predict prognosis in elderly glioblastoma patients

Abstract

It has been found that preoperative plasma IGFBP-2 levels correlate with prognosis in glioma patients. The prognostic value of plasma IGFBP-2 after postoperative combined radiotherapy and chemotherapy in glioma patients is unknown. Plasma IGFBP-2 levels in 83 glioblastoma patients after postoperative radiotherapy plus chemotherapy were analyzed using an IGFBP-2 ELISA kit. We found that after standard therapy plasma IGFBP-2 levels significantly correlated with the patient's age (R = 0.738, P<0.001) and Karnofsky performance status (KPS, R = -0.633, P<0.05). Cox proportional hazards models were used to calculate hazard ratios (HRs) of death according to plasma IGFBP-2 levels adjusted for patient clinical characteristics. Plasma IGFBP-2 levels significantly correlated with overall survival in glioblastoma patients (multivariate HR = 1.035; 95% CI, 1.024-1.047; P<0.001). The effect of plasma IGFBP-2 levels on survival seemed to differ according to patients' age. Among patients older than 60, high plasma IGFBP-2 levels were associated with a significant increase in overall mortality (HR = 1.097; 95% CI, 1.055-1.140; P<0.001). In contrast, plasma IGFBP-2 levels conferred no significant effect on mortality among patients younger than 60. Elevated plasma IGFBP-2 levels after combined postoperative radiotherapy and chemotherapy in elderly glioblastoma patients correlate with poor KPS score and predicts poor prognosis.

Figure 1. Correlation of plasma IGFBP-2 level with age and KPS in GBM patients after postoperative radiotherapy plus chemotherapy.

(A, B) Box plots demonstrate that older age (≥60 years) or lower KPS values (<78.7) correlate with markedly higher plasma IGFBP-2 level (ng/ml) respectively (P<0.05). (C, D) Box plots show that older age (≥60 years) or lower KPS values (<78.7) are associated with significantly shorter overall survival (P<0.05).

Figure 2. Correlation between clinical variables in the 83 GBM patients.

(A) After combined therapy plasma IGFBP-2 did not correlate with the extent of resection. (B) The extent of resection was not associated with age.

Figure 3. Kaplan-Meier curves for overall survival (OS) in GBM according to plasma IGFBP-2 levels after postperative radiotherapy plus chemotherapy.

(A) GBM patients with high plasma IGFBP-2 (>627.5 ng/ml) had a significantly worse OS than did GBM patients with low plasma IGFBP-2 (<627.5 ng/ml; P<0.001).(B) In GBM patients older than 60, high plasma IGFBP-2 (>687 ng/ml) was associated with significantly shorter OS (P<0.001). (C) In GBM patients younger than 60, plasma IGFBP-2 levels were not associated with OS.

Figure 4. The prognostic effect of plasma IGFBP-2 levels in different KPS groups.

Both in patients with KPS value less than 78.6 (A) and in patients with KPS value greater than 78.6 (B), elevated plasma IGFBP-2 levels after combined therapy were associated with shorter OS.