Abstract
Stereotactic irradiation (STI) alone as initial management has emerged as a widely practiced treatment modality for selected non-small cell lung cancer (NSCLC) patients with 1 to 10 small brain metastases. However, no randomized study comparing whole brain radiotherapy (WBRT) versus STI alone has been reported. To better assess the prognosis and guidance for optimal treatment selection of patients with brain metastases, we introduced the neutrophil to lymphocyte ratio (NLR) recognized as a poor prognostic factor in various cancers before cranial radiotherapy. A total of 193 consecutive NSCLC patients with 1 to 10 brain metastases with diameters less than 3cm in our institution were retrospectively analyzed. Patients with leptomeningeal metastasis, those who underwent craniotomy before RT and poor performance status were excluded. The evaluated prognostic factors for OS included gender, neurological deficit, histology, epidermal growth factor receptor (EGFR) mutation status, the number of target, target volume, previous EGFR-tyrosine kinase inhibitor treatment, recursive partitioning analysis (RPA) class and NLR. All factors with a p < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression and matched on a 1:1 basis for these prognostic variables. One hundred seven patients received STI and 86 received WBRT. The median follow-up for the entire cohort was 8.3 months (range, 0.8 - 154 months), 9.3 months for STI group and 7.7 months for WBRT group. Patient characteristics of the entire cohort were balanced in terms of gender, histology, EGFR status, and previous treatment. However, the rates of neurological deficit, the number of target, target volume, poor RPA class, and NLR were significantly larger in the WBRT group. Median overall survival (OS) in STI group and WBRT group was 10.1 months (range, 1.7 - 154 months) and 6.3 months (range, 0.8 - 112 months), respectively (p = 0.047). Univariate analysis showed that factors affecting OS were EGFR status, RPA class, solitary intracranial metastasis and NLR (p <0.05). Multivariate analysis found that NLR less than the cutoff value 3.6 (p = 0.0001) and solitary intracranial metastasis (p = 0.03) were independent favorable prognostic factors affecting OS. Propensity-score matching created a matched cohort of 92 patients (STI: n = 46 and WBRT: n = 46) with similar baseline characteristics. The survival benefit was not found in the STI group compared with the WBRT group (p = 0.56), whereas WBRT group reduced intracranial failure than STI group (p = 0.043). Adjusting for prognostic factors, treatment with either STI or WBRT did not result in any statistically significant difference in OS. NLR prior to cranial radiotherapy could be one of the strongest prognostic factors for NSCLC patients with limited brain metastases, and future prospective clinical investigation to validate its prognostic value is warranted.
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