Quantitative association between the in vitro human tumor stem cell assay and clinical response to cancer chemotherapy

Objective methods have been developed to quantitate results of the in vitro human tumor stem cell assay, the degree of the association between the in vitro assay and clinical response as well as the likelihood of response. Methods considered to quantitate in vitro assay data included first-order kinetics of percent survival with drug concentration, minimal percent of tumor colony-forming unit survival at low drug concentrations, and area under the in vitro percent survival-drug concentration curve. Based upon experimental data, the percent tumor colony survival and the area under the curve (i.e., in vitro sensitivity indices) were concluded to better account than other methods for the commonly observed nonlinear shape of the in vitro curves. The two methods also yielded equivalent quantitative descriptions of the in vitro data. A logistic regression model was used for explicit quantitation of the relationship between the in vitro sensitivity index and predicted probability of clinical response. Very high association was observed between the predicted in vivo and actual clinical response for the cytotoxic drugs considered. Incorporation of other pharmacologic and patient prognostic factors into the quantitative methods is discussed and shown to improve their effectiveness.