Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis,
Hu, M. D. Anderson Cancer Center, Cancer 2006;106:1998
Brain metastases occur in 30% to 50% of patients with nonsmall cell lung cancer (NSCLC) and confer a worse prognosis and quality of life. Historically, whole brain radiation therapy (WBRT) alone was offered as first-line therapy for the management of brain metastases. However, the landmark randomized trial by Patchell  comparing WBRT plus biopsy with WBRT plus surgical resection of single brain metastasis established surgery as the standard of care for patients with a single brain metastasis because it prolonged survival from 15 weeks to 40 weeks. In addition, the Radiation Therapy Oncology Group 95-08 trial demonstrated longer survival time for patients with solitary brain metastasis treated with stereotactic radiosurgery (SRS) and WBRT compared with WBRT alone (median survival time: 6.5 vs. 4.9 months). Additional studies have been published that support the use of SRS in patients with solitary brain metastases. These trials, which have demonstrated longer survival times for patients with aggressively treated single brain metastases, raise the question as to what level of treatment is appropriate for the primary site in NSCLC.

The optimal treatment for the primary site in patients with newly diagnosed NSCLC who have solitary brain metastases is not well defined, although several studies have shown that some patients might benefit from aggressive therapy. We sought to distinguish which patients with solitary brain metastases treated with surgery or SRS might benefit from aggressive treatment of their primary lung cancer.

The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13).

The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006).

By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.

Who Will Benefit from Aggressive Treatment

Billing  studied 28 patients with brain metastases from NSCLC who underwent craniotomy and resection of the lung primary tumor. Seventeen patients had N0 disease, 5 had N1 disease, and 6 had N2 disease. The 5-year survival rate for patients with N0 disease was 35% compared with 0% in patients with N1 or N2 lymph node disease. Negative lymph nodes appear to be an important prognostic factor for patients even in the presence of a single brain metastasis. Bonnette  observed median survival durations of 12.4 months in 103 patients treated with surgery for both the primary tumor and brain metastases, with a 5-year survival overall rate of 11%. We compared the current study group of patients with our database of 1002 lung cancer patients treated in the Department of Radiation Oncology at M. D. Anderson. The overall survival rate for patients with synchronous solitary brain metastasis was worse than that of the whole database (P<.01). But for the Stage I patients with synchronous brain metastases, there were no significant differences between the 2 groups of patients with or without brain metastases, , and the result was similar to Mountain However, there were significant differences of survival rates for Stage II and III patients between patients with or without brain metastases  Also, there were significant differences of overall survival rate and chest control for Stage I patients compared with Stage II and III (53% vs. 24%). The data suggest that aggressive treatment of both the brain metastases and primary NSCLC is indicated for thoracic Stage I patients.