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Comparison of Drug Sensitivity among Tumor Cells within a Tumor, between Primary Tumor and Metastases, and between Different Metastases in the Human Tumor Colony-forming Assay¹

Second Department of Surgery, Fukui Medical College, Fukui, Japan [N. T.]; Second Department of Surgery [Y. M., K. H., K. S., Y. H.], Department of Urology [T. H., O. Y.], and Experimental Radiology [O. N.], School of Medicine, Kyoto University, Kyoto, Japan; Kyoto National Hospital, Kyoto, Japan [T. S.]; and Division of Surgical Oncology, UCLA School of Medicine, Los Angeles, California 90024 [D. H. K., D. L. M.]

The human tumor colony-forming assay was used to compare chemosensitivity among tumor cells within a primary tumor, between primary tumor and metastases, and between different metastases. No significant differences in cloning efficiency were found in any of the three comparison studies. However, considerable differences in chemosensitivities were observed between different parts of the same tumor and between the primary tumor and metastases. Two different parts of the same tumor were comparably assayed for nine primary tumors. In nine paired samples which allowed in vitro drug sensitivity testing, there was no satisfactory correlation of sensitivity to cytostatic drugs. Cell suspensions were prepared from 28 primary tumors and from metastases taken from the same patient. In 14 paired samples which formed sufficient colonies for determination of drug effect, the data showed no satisfactory correlation of chemosensitivity between a primary tumor and its metastases. Both tumor samples from different metastatic sites of the same patient formed sufficient colonies in seven of eight instances. In the seven paired samples, there was strong association of chemosensitivity (p < 0.005). The results indicate that the reported discrepancies of in vitro and in vivo results in clinical trials using the tumor colony-forming assay for predicting resistance or sensitivity to cytostatic drugs may be due to therapeutic heterogeneity among tumor colony-forming units within a primary tumor and between a primary tumor and its metastases.

¹ Supported in part by the Veterans Administration Medical Research Service and by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan.

² To whom requests for reprints should be addressed.

Received 5/13/83. Accepted 2/28/84.