Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy. Identification of the optimal combination of chemotherapy and radiotherapy will require further trials.

The cell line data base described in this paper includes both clinical information about the patients from whom the cell lines were derived and information about the in vitro analyses performed of the cell lines.

These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.

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.Cancer 44:1885-1893, 1979.N THE PAST DECADE, there has been an in-I creasing awareness that central nervous system (CNS) metastases are a frequent complication of malignancies, particularly in lung, breast and hematologic cancers.5*9*24,25,26~30 In lung cancer patients, these metastases were more common in the small cell carcinoma of the lung (SCCL) than in the other histologic types.1~21~22'24,32,34 Autopsy studies demon- Accepted for publication November 24, 1978. strated brain metastases in as many as 50% of patients with SCCL.',21*22*32,34 Eighty percent of these metastases were clinically apparent, resulting in devastating morbidity and frequent mortality for these patients. CNS metastases in areas other than brain (leptomeningeal or spinal) were uncommon with an autopsy incidence of less than 5%.21,22Hansen suggested that the incidence of CNS metastases increased with lengthening s~rvival.'~ This phenomenon is reminiscent of the problem encountered in the treatment of hematologic malignancies in which intensive combination chemotherapy regimens controlled systemic diseases but did not affect CNS sanctuary sites.30 Prophylactic craniospinal radiotherapy andor prophylactic cranial irradiation (PCI) and intrathecal methotrexate therapy dramatically reduced the incidence of these CNS metastases, the majority of which were l e p t~m e n i n g e a l .~~

A staging system based on histopathologic evaluation of skin, lymph nodes, blood, and visceral sites provides more comprehensive prognostic information than clinical evaluation of skin disease and adenopathy. Patients may be divided at initial presentation into three prognostic groups: good-risk patients, who have plaque-only skin disease without lymph node, blood, or visceral involvement (median survival, greater than 12 years); intermediate-risk patients, who have cutaneous tumors, erythroderma, or plaque disease with node or blood involvement but no visceral disease or node effacement (median survival, 5 years); and poor-risk patients, who have visceral involvement or node effacement (median survival, 2.5 years).

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