Abstract
In patients with epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer (NSCLC) with brain metastases, it remains controversial whether the use of EGFR-tyrosine kinase inhibitor (TKI) alone without radiotherapy (RT) is an optimal approach. Here, we investigated the clinical outcomes according to the use of upfront RT as well as the subsequent therapy following intracranial progression. This single-centre retrospective study included a total of 173 patients who were treated with EGFR-TKI alone (TKI alone group) or with upfront whole-brain RT (WBRT) or stereotactic radiosurgery (SRS) followed by EGFR-TKI (RT plus TKI group). Clinical outcomes according to initial and subsequent therapies following intracranial progression were analysed. There was no significant difference in OS according to the use of upfront RT (TKI alone group, 24.5 months vs. WBRT group, 20.0 months vs. SRS group, 17.8 months; P = 0.186). Intracranial progression was found in 35 (32.7%) of 107 patients in the TKI alone group. Among them, 19 patients who received salvage RT had the better prognosis than others [median overall survival (OS); 28.6 vs. 11.2 months; P = 0.041]. In the RT plus TKI group, 12 (18.1%) of the 66 patients experienced intracranial progression and 3 of them received salvage RT (median OS; 37.4 vs. 20.0 months; P = 0.044). In multivariate analysis, upfront WBRT was associated with trends towards a lower probability of intracranial progression, whereas upfront SRS was found to be an independent risk factor for poor OS. In conclusion, using EGFR-TKI alone for brain metastasis in EGFR-mutant lung cancer patients showed outcomes comparable to those using upfront RT followed by EGFR-TKI. Patients who could not receive salvage RT following intracranial progression had the worst survival regardless of the type of initial treatment.
Highlights
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]; patients with brain metastases have poor outcomes compared with those without brain metastases [2]
The primary outcome of this study was the comparison of overall survival (OS) in patients according to the type of initial treatment (EGFR-tyrosine kinase inhibitor (TKI) alone, whole-brain RT (WBRT) followed by epidermal growth factor receptor (EGFR)-TKI and stereotactic radiosurgery (SRS) followed by EGFR-TKI) or the presence of salvage RT
Of the 173 patients, 107 (61.8%) received EGFR-TKI alone, 36 (20.8%) were treated with WBRT followed by EGFR-TKI and 30 (17.3%) were treated with SRS followed by EGFR-TKI
Summary
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]; patients with brain metastases have poor outcomes compared with those without brain metastases [2]. 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]. The median overall survival (OS) has recently been increasing in patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and brain metastases due to the introduction of targeted therapy [5]. Upfront EGFR-TKI alone without local RT has been used [8,9,10,11] with the advantage of avoiding radiation-induced neurotoxicity until tumour progression [12,13]. Proper management of EGFR-mutant NSCLC with brain metastases remains controversial
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