The Importance of Brain Metastasis in EGFR Mutation Positive NSCLC Patients

Abstract

Introduction. Brain metastasis is a poor prognostic marker in lung cancer. However it is not known whether amongst patients with EGFR mutation those with brain metastases have a worse outcome. Methods. We compared the survival outcomes between EGFR mutation positive patients with and without brain metastases. In this retrospective analysis of prospective database of all metastatic lung cancer patients at our centre between July 2009 and December 2012, patients were treated with either combination chemotherapy or oral TKI. All patients with brain metastases received whole brain radiation. Kaplan Meier method was used for survival analysis and compared using log rank test. Results. 101 patients with EGFR mutated, metastatic lung cancer were studied. Fourteen had brain metastases and 87 did not. The common EGFR mutations were exon 19 deletion (61.3%) and exon 21 L858R mutation (28.7%). Overall response was 64% in extracranial metastasis group as compared to 50% in brain metastasis group. There was a significant worsening of median OS in the patients with brain metastases (11.6 months) compared with only extracranial metastases (18.7 months), P = 0.029. Conclusion. Amongst patients with EGFR mutant NSCLC, the presence of brain metastases leads to a worse outcome as compared to patients with extracranial metastases alone.

Outcomes according to initial and subsequent therapies following intracranial progression in patients with EGFR-mutant lung cancer and brain metastasis

“…In patients with non-small-cell lung cancer (NSCLC), the incidence of initial brain metastases at the time of lung adenocarcinoma diagnosis is approximately 20% [1]; furthermore, patients with brain metastases have poor outcomes compared with those without brain metastases [2]. Although radiotherapy (RT) or surgical resection has been the conventional treatment for brain metastases, patient survival rate remains unsatisfactory and severe deterioration of general condition has often been observed owing to neurotoxicity after RT [3,4].…”

Prognostic impact of pleural effusion in EGFR‐mutant non‐small cell lung cancer patients without brain metastasis

“…Although several prognosis factors have been reported, the metastatic site is one of the most important among these factors. Indeed, metastatic sites, such as the brain, bone, and liver, as well as pleural effusion, were reported as predictors of poor prognosis in advanced EGFR ‐mutant NSCLC . Among these sites, the median overall survival (OS) was significantly shorter in patients with brain metastasis than in those without brain metastasis.…”

“…Indeed, metastatic sites, such as the brain, bone, and liver, as well as pleural effusion, were reported as predictors of poor prognosis in advanced EGFR-mutant NSCLC. [9][10][11][12][13] Among these sites, the median overall survival (OS) was significantly shorter in patients with brain metastasis than in those without brain metastasis. Specifically, the presence of brain metastasis has been previously confirmed to be a prognosis factor in a multivariate analysis.…”

Impact of metastatic status on the prognosis of EGFR mutation‑positive non‑small cell lung cancer patients treated with first‑generation EGFR‑tyrosine kinase inhibitors

“…The toxicities of EGFR-TKIs are decreased compared with those of cytotoxic drugs and patients can achieve a good quality of life while using them (8,12). In patients treated with first generation EGFR-TKIs, brain, bone and liver metastasis and pleural effusion (PE) predicted a poorer prognosis compared with patients without these metastasis (13)(14)(15)(16)(17). However, few reports concern the association between the site of metastasis and prognosis (18,19).…”