Abstract 1291: Applicability of integrative tumor response assays for recurrent colorectal cancer

Abstract

Abstract Introduction Drug response assays use autologous viable tumors to evaluate susceptibility to specific agents in vitro. Histoculture drug reponse assay (HDRA) is a representative methyl thiazolyl-diphenyl-tetrazolium bromide (MTT) assay, which has the advantage of more correctly reflecting the in vivo microenvironment. Many studies showed 66-92% of accuracy rates for clinical correlation of chemotherapy in solid tumors including colorectal cancer (CRC). However, in recurrent cases of metastatic CRC, there is no usable assay to predict second-line chemo-sensitivity. Thus, authors invented novel technique, the integrative tumor response assay (ITRA), can identify drug responses for both first- and second-line chemotherapy simultaneously. We investigated the chemo-sensitivity to clinically used regimens using ITRA of samples from patients with metastatic CRC, and compared their chemo-sensitivity with the observed clinical response. Methods A total of 129 patients with metastatic CRC were prospectively enrolled. First-stage HDRAs were performed using 5-fluorouracil with leucovorin and oxaliplatin (FX) or irinotecan (FR). Second-stage HDRAs (ITRA) were done for survived cells after first-stage HDRA, using FX, FR, and their combinations with bevacizumab and cetuximab. The inhibition rate of tumor growth (IR) cut-off value for a positive response was determined to be ≥ 30%. For clinical validation, treatment responses of chemotherapy were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). The primary endpoint of this study was a correlation between the ITRA results and the clinical response in the response rate (RR). This was defined as positive for the effect of chemotherapy for tumor responses between complete response (CR) and partial response (PR). Results Among 129 used samples, ITRA failure was 9 (7%), due to deficient volume of samples. Out of 79 evaluated first-line chemotherapeutic regimes, RR was 53% (42/79). The correlation rate of HDRA for first-line chemotherapy was 70.9% (56/79), with a 71.4% (30/42) of sensitivity and 70.3% (26/37) of specificity. For 42 cases completing second-line chemotherapy, RR was 43% (18/42). The accuracy rate of ITRA for second-line chemotherapy was 61.9% (26/42), with a 44.4% (8/18) of sensitivity and 75% (18/24) of specificity. Conclusions ITRA might be further developed to be a feasible and useful technique for predicting therapy efficacy and selecting the appropriate anticancer regimen for individual patients despite its relatively low accuracy. Citation Format: Yong Sik Yoon, Jin Cheon Kim. Applicability of integrative tumor response assays for recurrent colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1291.