Brain Metastasis is an Early Manifestation of Distant Failure in Stage III Nonsmall Cell Lung Cancer Patients Treated With Radical Chemoradiation Therapy

Abstract

To evaluate the patterns of distant relapse, focusing on brain metastasis, in patients with stage III nonsmall cell lung cancer (NSCLC) treated with radical chemoradiation therapy (CRT). The British Columbia Cancer Agency provincial database identified 2268 patients presenting with stage III NSCLC between January 1, 1990 and December 31, 2000. Of these, 120 patients received radical CRT, forming the study cohort. Variables analyzed included gender, age, Eastern Cooperative Oncology Group performance status, stage, histology, sites of metastasis, and survival. Univariate and multivariate analyses were performed. The study cohort comprised 59 men and 61 women, median age 54.5 years. There were 74 stage IIIA and 46 stage IIIB cases. Histologic subtypes were squamous cell carcinoma (n = 29), adenocarcinoma (n = 53), and other non-squamous histologies (n = 38). Median follow-up time was 17.7 months. Median overall survival time was 19.2 months. Thirty-two patients (27%) developed brain metastasis. Non-brain metastases occurred in 51 patients (42%). No variables were statistically significantly associated with the risk of developing brain metastasis. Trends for higher risks of brain metastasis were observed with younger age (P = 0.09), and poor performance status (P = 0.07). Brain metastasis risk was highest during the first 10 months, progressively declining thereafter. Stage III NSCLC patients treated with CRT have high risks of brain metastasis which persist during the first 10 months after diagnosis. Studies evaluating cranial prophylaxis will be relevant for these patients, particularly during this early period. Novel systemic therapies continue to be needed because non-brain metastases still represent the majority of distant recurrences.