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High Risk of Brain Metastases in Surgically Staged IIIA Non–Small-Cell Lung Cancer Patients Treated With Surgery, Chemotherapy, and Radiation

From the Departments of Radiation Oncology and Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center; Hematology-Oncology Unit, Department of Medicine, Massachusetts General Hospital; Division of Thoracic Surgery, Brigham and Women's Hospital; and Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA

Address reprint requests to Raphael Bueno, MD, Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115; e-mail: rbueno{at}partners.org

PURPOSE: Lung cancer is the leading cause of cancer mortality in the United States. We sought to review our experience with surgically staged IIIA (N2) non–small-cell lung cancer (NSCLC), focusing on the patterns of failure in consecutively treated patients from 1988 to 2000.

PATIENTS AND METHODS: The records of 177 patients were reviewed. Collected data included stage, histology, use of chemotherapy and radiation, initial and subsequent sites of failure, and survival. One hundred twenty-four patients have died; follow-up time is 35 months among the remaining patients.

RESULTS: The median survival from the time of surgery was 21.0 months, with a 3-year overall survival (OS) of 34%. Nodal downstaging to N0 disease correlated with OS and progression-free survival (PFS; P < .001). The most common site of recurrence was the brain. Thirty-four percent of patients recurred in the brain as their first site of failure, and 40% of patients developed brain metastases at some point in their course. In patients with nonsquamous histology and residual nodal involvement after neoadjuvant therapy, the risk of brain metastases was 53% at 3 years.

CONCLUSION: Patients treated with neoadjuvant therapy for N2-positive stage IIIA NSCLC enjoy an advantage in both OS and PFS if their lymph node status is downstaged to N₀. Because brain metastases constitute the most common site of failure in these patients, future studies focusing on prophylaxis of brain metastases may improve the outcome in patients with stage IIIA NSCLC.

Supported in part by a grant from the Lowe Thoracic Oncology Program at the Dana-Farber Cancer Institute (R.B.).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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