Influence of the Timing of Leptomeningeal Metastasis on the Outcome of EGFR-Mutant Lung Adenocarcinoma Patients and Predictors of Detectable EGFR Mutations in Cerebrospinal Fluid.

BACKGROUND: We aim to evaluate the influence of the timing of leptomeningeal metastasis (LM) occurrence on the outcome of EGFR-mutant lung adenocarcinoma and to explore the predictors of detectable EGFR mutation in the cerebrospinal fluid (CSF). METHODS: EGFR-mutant lung adenocarcinoma patients with cytologically confirmed LM were included for analysis. EGFR mutation in CSF was detected by MALDI-TOF MS plus PNA. RESULTS: A total of 43 patients was analyzed. Of them, 8 (18.6%) were diagnosed with LM prior to first-line EGFR-TKI treatment (early onset), while 35 patients (81.4%) developed LM after first-line EGFR-TKI treatment (late onset). Multivariate analysis suggested that both late-onset LM (aHR 0.31 (95% CI 0.10-0.94), p = 0.038) and a history of third-generation EGFR-TKI treatment (aHR 0.24 (95% CI 0.09-0.67), p = 0.006) independently predicted a favorable outcome. EGFR mutation detection sensitivity in CSF was 81.4%. The radiological burden of LM significantly correlated with CSF tumor cell counts (p = 0.013) with higher CSF tumor cell counts predicting a higher detection sensitivity of EGFR mutation (p = 0.042). CONCLUSIONS: Early onset LM was an independently poor prognostic factor. A higher radiological severity score of LM could predict higher tumor cell counts in CSF, which in turn were associated with a higher detection rate of EGFR mutation.

Successful treatment of multifocal bronchioloalveolar cell carcinoma with ZD1839 (Iressa) in two patients.

Multifocal bronchioloalveolar cell carcinoma (BAC) is a rare condition that often presents as bilateral lung infiltrates unsuitable for surgical and radiological treatment, with poor response to conventional chemotherapies. Epidermal growth factor receptor (EGFR) pathways are closely related to the proliferation and metastasis of cancer cells. ZD1839 (Iressa) is a quinazoline-derived, orally active, selective inhibitor of the EGFR tyrosine kinase that shows promising effects in the treatment of non-small cell lung cancer. We report 2 cases of multifocal BAC successfully treated with ZD1839. Both patients had advanced disease, and had productive cough for more than 1 year. After the diagnosis of BAC, the first patient received chemotherapy, but was unresponsive. Within 2 weeks of starting treatment with ZD1839 250 mg per day, the amount of bronchorrhea decreased. Two months after the start of ZD1839 treatment, image study showed a marked decrease of lung infiltrates. The second patient developed respiratory failure after an operation on the spine. He received ZD1839 250 mg daily via nasogastric tube. Two weeks after the start of treatment, his dyspnea had improved and he was weaned from the mechanical ventilator. The side effects of ZD1839 treatment in these 2 patients consisted only of dry skin and acne over the face, trunk, and periungual areas. Although the precise mechanisms of the antitumor effects of ZD1839 remain unclear, these results suggest a role for the agent in the management of patients with advanced multifocal BAC.