Studies on the diagnosis and treatment of human lung cancer using double-layered soft agar cloning assay

The extent of tumor dissemination at the time of diagnosis is an important predictor for survival of lung cancer patients. In vitro sensitivity to drugs is helpful for successful chemotherapy of advanced lung cancer patients. A major objective of the present study was to clarify the significance of direct cloning assay for the detection of metastatic sites as well as for the selection of sensitive drugs for individual patients. Tumor cell colony growth was evaluated in an enriched double-layered soft agar system. Colonies were successfully grown from 5 of 7 cytology positive effusions, and 4 of 5 histology/cytology positive bone marrow aspirates. Two of 17 histology/cytology negative bone marrow aspirates yielded colonies, whereas 5 cytology negative effusions yielded no colonies. Colony growth was observed in 3 of 5 tumor specimens obtained surgically. For in vitro chemosensitivity, tumor cells were exposed for 1 hour prior to plating. Although colonies were successfully grown from specimens of 5 patients, none of them were sensitive to the drugs tested. Three of the 5 patients were treated with intensive combination chemotherapy including therapy with drugs which had been defined to be resistant in the in vitro chemosensitivity test and no response was observed in these cases. In this sense, in vitro sensitivity correlated with in vivo sensitivity.