Combination of Whole-Brain Radiotherapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Improves Overall Survival in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases.

Chen Chen,Chuang Chuang,Huang Huang,Chong Chong,Hung Hung,Lee Lee

doi:10.3390/cancers11081092

Abstract

Brain metastases (BM) cause morbidity and mortality in patients with non-small cell lung cancer (NSCLC). The use of upfront epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and withholding of whole-brain radiation therapy (WBRT) is controversial. We aim to investigate the impact of WBRT on overall survival (OS). After screening 1384 patients, a total of 141 EGFR-mutated patients with NSCLC and BM were enrolled. All patients received EGFR-TKIs between 2011 and 2015. Ninety-four patients (66.7%) were treated with WBRT (TKI + WBRT group). With a median follow-up of 20.3 months (95% confidence interval (CI), 16.9–23.7), the median OS after the diagnosis of BM was 14.3 months (95% CI, 9.5 to 18.3) in the TKI + WBRT group and 2.3 months (95% CI, 2 to 2.6) in the TKI alone group. On multivariate analysis, WBRT (p < 0.001), female, surgery to primary lung tumor, and surgery to BM were associated with improved OS. The 1-year OS rate was longer in the TKI+WBRT group than that in the TKI alone group (81.9% vs. 59.6%, p = 0.002). In conclusion, this is the first study to demonstrate the negative survival impact from the omission of WBRT in patients with EGFR-mutant NSCLC.

Highlights

Lung cancer is a leading cause of cancer incidence and mortality [1], and is the most common primary site of brain metastases (BM) [2]
The median duration of tyrosine kinase inhibitor (TKI) use was 13.2 months (95% confidence interval (CI), 10.1 to 16.2) in TKI + whole-brain radiotherapy (WBRT) group and 10 months in the TKI alone group
The mean durations of TKI use were 18.1±15.1 months and 15.4 ± 16.4 months for patients with and without WBRT, respectively (p = 0.327). In this cohort of 141 patients, 52 patients had more than one line of TKIs due to intolerance or disease progression

Summary

Introduction

Lung cancer is a leading cause of cancer incidence and mortality [1], and is the most common primary site of brain metastases (BM) [2]. The mainstay of treatment for BM has been surgery, whole-brain radiotherapy (WBRT) or stereotactic radiosurgery performed alone or in combination. WBRT targets any micro-metastases not detected on imaging, prevents intracranial recurrence, and reduces the risk of deaths due to neurological cause [3]. Because BM causes neurological decline, WBRT improves neurological function with minimal complications [4,5]. In 1954, it was reported to lessen headache, aphasia, hemiplegia, paralysis, blurred vision and incontinence [4]. Radiotherapy (RT)-induced dementia in patients cured of BM was 1.9 to 5.1% [6]

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