J Korean Neurosurg Soc.  2017 Jan;60(1):21-29. 10.3340/jkns.2016.0404.005.

The Influence of Biomarker Mutations and Systemic Treatment on Cerebral Metastases from NSCLC Treated with Radiosurgery

• Lee MH
• Kong DS
• Seol HJ
• Nam DH
• Lee JI

• KMID: 2365583
• DOI: http://doi.org/10.3340/jkns.2016.0404.005

Abstract

OBJECTIVE
The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments.
METHODS
We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated.
RESULTS
The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified.
CONCLUSION
The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.

Keyword

Non-small cell lung cancer; EGFR; K-ras; ALK; Gamma knife radiosurgery

MeSH Terms

Biomarkers
Brain
Carcinoma, Non-Small-Cell Lung
Follow-Up Studies
Humans
Lymphoma
Medical Records
Multivariate Analysis
Neoplasm Metastasis*
Phosphotransferases
Prognosis
Radiosurgery*
Receptor, Epidermal Growth Factor
Recurrence
Retrospective Studies
Salvage Therapy
Biomarkers
Phosphotransferases
Receptor, Epidermal Growth Factor

Figure

• 

  Fig. 1 Kaplan-Meier curve comparing overall survival and salvage treatment-free survival according to the manner of using target agents. Group A : patients who never received target agents; Group B : patients who received target agents before GKS or within 30 days; Group C : patients received target agents 30 days after receiving GKS. GKS : gamma knife radiosurgery.

• 

  Fig. 2 Kaplan-Meier curve comparing salvage treatment-free survival of the influence of target agents to the pattern of progression, local recurrences and new lesion development. Group A : patients who never received target agents; Group B : patients who received target agents before GKS or within 30 days; Group C : patients received target agents 30 days after receiving GKS. GKS : gamma knife radiosurgery.

Reference

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