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Abstract
It is well-known that genomic mutational analysis plays a significant role in patients with NSCLC for personalized treatment. Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS. Patients with BM and treated by SRS were eligible in this study. The primary endpoint was overall survival (OS). Cox regression models were used to identify independent prognostic factors. A survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC), and calibration curve. From January 2016 to December 2019, a total of 356 BM patients were eligible. The median OS was 17.7 months [95% confidence interval (CI) 15.5–19.9] and the actual OS at 1- and 2-years measured 63.2 and 37.6%, respectively. A nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, gene mutation status, and serum lactate dehydrogenase. The nomogram was validated in a separate cohort and demonstrated good calibration and good discriminative ability (C-index = 0.780, AUC = 0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced when compared with classical prognostic indices, including the Graded Prognostic Assessment (0.708), recursive partitioning analysis (0.587), and the SRS (0.536). Kaplan–Meier curves showed significant differences in OS among the stratified low-, median- and high-risk groups (P < 0.001). In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry, and molecular biological surrogates. Although this nomogram should be validated by independent external study, it has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.
Highlights
Brain metastases (BM) represent the most common intracranial tumors in adults, which occur up to 10-times more frequently than primary central nervous system tumors
Given the increasingly recognized role of stereotactic radiosurgery (SRS) in the treatment of brain metastases, specific scoring criteria integrating a spectrum of volumetric, physiological, clinical chemistry, and molecular biological surrogates for precise assessment of patients following
We demonstrated that the cumulative tumor volume, driver gene mutation status, serum lactate dehydrogenase (LDH), and Karnofsky Performance Status (KPS) were significant prognostic factors for brain metastases after SRS
Summary
Brain metastases (BM) represent the most common intracranial tumors in adults, which occur up to 10-times more frequently than primary central nervous system tumors. Several well-known prognostic indices are widely utilized for clinical decision-making and outcome research, and include recursive partitioning analysis (RPA), the Score Index for Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), and the Graded Prognostic Assessment (GPA) [4,5,6]. These prognostic scoring systems were established by integrating several clinicopathological features such as age, the KPS, the number of metastatic lesions, extracranial metastases, and the control of the primary tumor, and allowed a certain degree of prognostic discrimination. In the light of new knowledge in cancer biology, the incorporation of molecular and physiological tumor characteristics into clinical stratification schemes may further advance the prognostic predictive capacity for brain metastases patients who received SRS
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