3D Sponge-Matrix Histoculture

Robert M. Hoffman

Gelfoam® histoculture was utilized to develop the histoculture drug response assay (HDRA) for head and neck cancer. Specimens of head and neck tumors were evaluated for sensitivity to the following drugs: cisplatinum (CDDP), 5-fluorouracil (5-FU), and the combination of CDDP and 5-FU. In the first clinical study at UCSD, 10 of 12 patients with tumors that were drug sensitive in Gelfoam® histoculture had either complete or partial response clinically. Comparisons of HDRA results, obtained with [3H]thymidine incorporation as the endpoint were made with clinical responses, i.e., complete response, partial response, or no response. The overall accuracy of the HDRA was 74% in this correlative clinical trial; the predictive positive value was 83%, the sensitivity was 71%, and the specificity was 78%. Seven of 11 patients with HDRA-resistant tumors demonstrated no response for a predictive negative value of 64%. In a subsequent study at Memorial Sloan Kettering Cancer Center, tumor specimens from 41 to 42 patients undergoing treatment for head and neck cancer were successfully evaluated by the HDRA. The histocultured tumors were treated with 5-FU and/or CDDP and a control group received no drug treatment. After completion of drug treatment, the relative cell survival in the tumors was determined using the MTT endpoint. Sensitivity was defined as a tumor inhibition rate (IR) of greater than 30%. Survival comparisons were performed using the generalized Wilcoxon test for the comparison of Kaplan-Meier survival curves. Resistance to 5-FU was observed in 13 cases (32%), to CDDP in 13 cases (32%), and to both agents in 11 cases (27%). The 2-year cause-specific survival was significantly greater for patients sensitive to 5-FU than patients who were resistant (85% vs. 64%), CDDP (86% vs. 64%), or both agents (85% vs. 63%). These results demonstrate the clinical usefulness of the HDRA for head and neck cancer.