3D Sponge-Matrix Histoculture

Robert M. Hoffman, Phill-Seung Jung, Moon-Bo Kim, Joo-Hyun Nam

The histoculture drug response assay (HDRA) has been correlated clinically to a number of cancer types (please see Chaps. 7 - 11 of the present volume). The present chapter reviews the clinical trials of the HDRA for ovarian cancer. A prospective clinical trial of the HDRA for advanced epithelial ovarian cancer (AEOC) was performed at Asan Medical Center, Seoul, Korea. The clinical trial compared the efficacy of first-line therapy paclitaxel and carboplatinum in the HDRA and the clinical response for the patients whose tumors were tested in the HDRA. A series of patients (104) were treated with adjuvant combination chemotherapy of paclitaxel and carboplatinum after primary cytoreductive surgery. Tumor fragments were cultured on Gelfoam® and tested with paclitaxel and carboplatinum and evaluated with the MTT endpoint. Patients were categorized into two groups as either sensitive to both drugs (SS) or not sensitive to one or both drugs (R) based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group, 29.2% vs. 69.8%, respectively. The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs. 16.0 months, respectively. In another clinical trial, the HDRA was performed on 85 cases of ovarian cancer and 97% were evaluable. HDRA results were correlated to clinical response of 15 patients who received cisplatinum-based therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true-positive rate was 88%, the true-negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients.