Simultaneous in vitro drug sensitivity testing on tumors from different sites in the same patient

A human tumor cloning assay was used to analyze drug sensitivity profiles for 99 pairs of tumor samples taken simultaneously from the same patient. These pairs included two areas of the same primary (12 pairs), primary tumor versus metastasis (29 pairs), and metastasis versus metastasis (45 pairs). In addition, to assess variability in the culture and sensitivity techniques, 13 specimens were divided equally and processed twice. One hundred fourteen evaluable drug sensitivity tests were performed on the specimen pairs. Drug sensitivity profiles for the same specimen processed twice demonstrated good agreement (P = 0.03). Sensitivity profiles from two different areas of the same primary were also quite similar (P = 0.002). However, when one sampled a primary tumor and its metastasis for drug sensitivity testing, the agreement (in terms of percent survival) was poor (P = 0.84). Agreement was also poor for drug sensitivity profiles of one metastasis versus another metastasis (P = 0.39). This heterogeneity in drug sensitivity profiles of primary versus metastasis and of metastasis versus metastasis could account for some of the false positives and false negatives noted in clinical correlation trials with the cloning assay. It may also have implications for adjuvant treatment programs where chemosensitivity of the primary tumor can be determined, but will probably not be predictive for chemosensitivity of the micrometastases.