CNS metastases in small cell bronchogenic carcinoma. Increasing frequency and changing pattern with lengthening survival

The records of 209 patients with small cell bronchogenic carcinoma were reviewed to define the problem of CNS metastases. CNS metastases were documented in 102 of these patients (49%) and 55 of 85 autopsied patients had CNS metastases (65%). The probability of developing a CNS metastasis increased with lengthening patient survival to a level of 80% after 2 years. As in other series, the cerebrum was the most frequently involved site. In addition, leptomeningeal, spinal, pituitary, and cerebellar metastases, and multiple sites of involvement were far more common than in previously reported series. Patients with bone marrow and liver metastases at initial staging were more likely to develop CNS metastases than those without these metastases. Bone marrow involvement was strongly associated with the development of leptomeningitis. Systemic chemotherapeutic agents which cross the blood brain barrier did not prevent the high frequency of CNS metastases. Pathologic studies suggested cerebral and leptomeningeal metastases may arise via hematogenous spread or via penetrating vessels from bone marrow to the subarachnoid space. Therapy for CNS metastases provided adequate palliation, and the majority of deaths were due to systemic rather than neurologic disease. Nevertheless, prophylactic therapy appears necessary at present to prevent the morbidity associated with these metastases. As further improvements in systemic therapy evolve, CNS prophylaxis may also be required for “cure” of patients with small cell lung cancer.