Heterogeneity of human metastatic clones by in vitro chemosensitivity testing. Implications for the clinical application of the clonogenic assay.

To determine whether in vitro chemosensitivities of clones from metastases of human tumors varied, biopsy specimens of two separate metastatic lesions were obtained from 75 patients. Significant tumor growth (greater than 30 colonies per plate) occurred in both specimens in 49 of the 75 patients. Biopsies were performed simultaneously in 22 patients (synchronous) and sequentially in 27 patients (metachronous). Tumor samples were scored as being resistant (less than 50% inhibition of colony formation) or sensitive (greater than 50% inhibition) to each drug. The two tumor samples from each patient were compared for differences in sensitivity after exposure with standard panels of chemotherapeutic agents. A total of 272 individual drug comparisons were possible. Variations were evident in 49 (40%) of 121 metachronous drug comparisons and in 42 (28%) of 151 synchronous drug comparisons. We concluded that multiple metastases of human tumors can vary in chemosensitivity in vitro; this finding seemed to reflect the heterogeneity of metastatic clones.