Brain Metastases After Definitive Concurrent Chemoradiotherapy in Patients with Stage III Lung Adenocarcinoma: Carcinoembryonic Antigen As a Potential Predictive Factor

The predictive factors for the development of brain metastases in patients with stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy remain unclear. Several studies have suggested adenocarcinoma as a predictive factor of brain relapses. In the current analysis, we tried to identify the factors associated with brain metastases in stage III lung adenocarcinoma. The demographic and clinical characteristics, site and date of recurrence, and date of death were reviewed in patients with unresectable stage III lung adenocarcinoma who underwent concurrent platinum-based chemoradiotherapy. In total, 116 patients were identified with a median (range) age of 57 (35-74) years. Of these, 86 (74%) were men, all patients had platinum-based chemotherapy, and 100 (86%) received a total dose of 60 Gy in 30 fractions as definitive thoracic radiotherapy. Of the 95 patients with disease progression or recurrence, 19 (16%) developed brain metastases as the sole site of initial recurrence. A total of 43 (37%) patients developed brain metastases at some time during follow-up. Time to brain metastases was significantly associated with the pretreatment carcinoembryonic antigen (CEA) value, with a hazard ratio (95% confidence interval) of 2.64 (1.39-5.02, P = 0.003). Patients who developed brain metastases as the first recurrent site had marginally better survival (log-rank test, P = 0.066) than those with metastases other than brain. In conclusion, stage III lung adenocarcinoma patients with an elevated CEA value before treatment had a higher risk of developing brain metastases after chemoradiotherapy. Further effort is mandatory to control brain metastases in this patient population by a therapeutic strategy based on the tumor histology and pretreatment CEA value.