Prognostic Significance of the Cachexia Index in Patients with Non-Small-Cell Lung Cancer and Brain Metastases after Stereotactic Radiotherapy

Abstract

Background: The cachexia index (CXI) has been proposed as a novel biomarker of cancer cachexia. We aimed to investigate the association between CXI and survival outcomes after stereotactic radiotherapy (SRT) in patients with non-small cell lung cancer (NSCLC) and brain metastases.

Methods: Data from 145 patients with NSCLC, who underwent SRT for brain metastases between April 2016 and August 2020, were retrospectively analyzed. Cachexia index was calculated as skeletal muscle index (SMI) × serum albumin level/neutrophil-to-lymphocyte ratio, whereas SMI was calculated from computed tomography images captured at the L1 level. Kaplan-Meier curves and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). The prognostic values of CXI and other cachexia biomarkers were assessed using receiver operating characteristic (ROC) curve analysis.

Results: Lower pretreatment CXI (<30.8) was significantly associated with older age (P = .039), lower Karnofsky performance score (P = .009), and a high likelihood of extracranial metastases (P = .001). Patients with a lower pretreatment CXI had a significantly shorter PFS and OS than those with a higher CXI (P < .001). Multivariate analysis revealed that pretreatment CXI was an independent risk factor for both PFS, hazard ratio (HR) = 2.375; 95% confidence interval (CI) = 1.610-3.504; P < .001, and OS, HR = 2.340; 95% CI = 1.562-3.505; P < .001. Compared with other biomarkers, pretreatment CXI had the highest area under the ROC curve value for prognostic assessment, reaching 0.734. Moreover, the loss of CXI was a strong risk factor for survival independent of pretreatment CXI (P = .011).

Conclusions: Cachexia index may serve as a clinically useful tool for predicting survival outcomes of patients with NSCLC and brain metastases who undergo SRT.

Keywords: Non-small cell lung cancer; brain metastases; cancer cachexia; stereotactic radiotherapy; survival.

Figure 1.

Example of body composition analysis for measurement of skeletal muscle area.

Figure 2.

Kaplan-Meier curves for progression-free survival (A) and overall survival (B) in patients with low and high CXI. CXI indicates cachexia index.

Figure 3.

Areas under the receiver operating characteristic curves for 1-year progression-free survival. CI indicates confidence interval; CONUT, controlling nutritional status; CXI, cachexia index; GNRI, geriatric nutritional risk index; NPS, Naples prognostic score; PNI, prognostic nutritional index; ROC, receiver operating characteristic; SII, systemic immune inflammatory index.