Predicting resistance to platinum-containing chemotherapy with the ATP tumorchemosensitivity assay in primary ovarian cancer

Aims: Most patients with primary epithelial ovarian cancer (PEOC) treated with carboplatin/paclitaxel will relapse between one to two years. Our purpose was to define the optimal calculation method for the ATP Tumor Chemosensitivity assay (ATP-TCA) applied to PEOC treated with platinum-containing chemotherapy and to analyze its predictive relevance. Material and Methods: ATP-TCA results from 80 PEOC specimens were analyzed applying three different methods: 50% inhibition concentration, sensitivity index (IndexSUM), and area under curve by testing multiple cut-off levels. Correlation between in vitro results and clinical outcome was performed for 61 (76%) patients by univariate and multivariate analysis. Tumor recurrence 6 months after chemotherapy was classified as platinum-resistance. Results: The IndexSUM set at >250 had the highest test sensitivity, specificity, positive and negative predictive value of 90%, 43%, 62% and 81%, respectively. Patients whose tumors were shown to be resistant by ATP-TCA had a higher risk for recurrence (RR) compared to those who tested as sensitive (p<0.003, RR=3.3, 95% CI=1.2–9.4). This result was confirmed after adjustment for FIGO stage by logistic regression (p<0.004, Odds ratio=8.3, 95%CI=1.9–35.5). In multivariate analysis ATP-TCA and the FIGO-stage were independent predictive factors of early recurrence. Conclusion: ATP-TCA results in combination with the use of IndexSUM >250 are best able to predict platinum resistance.

ovarian cancer - platinum-containing chemotherapy - tumorchemosensitivity assay