Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer: clinical implications for the subsequent management of the brain.

BACKGROUND: The incidence and pattern of brain metastases was analyzed among patients who achieved a pathological complete response (pCR) after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced nonsmall-cell lung cancer (NSCLC).
METHODS: Between 1990 and 2004, 211 patients were treated with neoadjuvant therapy before surgical resection for stage III NSCLC. The clinical course of 51 patients who demonstrated a pCR were reviewed. The neoadjuvant regimen consisted of either chemotherapy (29 patients) or chemoradiotherapy (22 patients). Histology was 45% adenocarcinoma, 41% squamous cell, and 14% large cell carcinoma. No patient received prophylactic cranial irradiation (PCI).
RESULTS: Overall survival at 1, 3, and 5 years was 82%, 63%, and 42%, respectively. The most common site of initial recurrence was the brain. Twenty-two (43%) patients developed brain metastasis as the site of first failure, which represented 71% of all isolated recurrences. Ultimately, 28 (55%) patients developed brain metastases at some point during their clinical course. The 5-year estimates of brain metastasis-free survival for patients with squamous and nonsquamous cancers were 57% and 34%, respectively (P = .02). Median survival from the time of brain metastasis was 10 and 5 months for those with isolated and nonisolated recurrences, respectively.
CONCLUSION: Patients with a pCR after multimodality therapy for locally advanced NSCLC are at excessively high risk for the subsequent development of brain metastases. Implications for management strategies including PCI and stereotactic radiosurgery (SRS) are discussed.