Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study

PURPOSE: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. MATERIALS AND METHODS: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. RESULTS: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. CONCLUSIONS: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

Predictive Value of In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay in Advanced Gastric Cancer Patients Who Received Oral 5-Fluorouracil after Curative Resection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy. MATERIALS AND METHODS: Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful. RESULTS: The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant). CONCLUSION: Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.

Heterogeneity of Adenosine Triphosphate-Based Chemotherapy Response Assay in Colorectal Cancer - Secondary Publication

PURPOSE: Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology that can individualize chemotherapy for patients with lung, stomach, or breast cancer. This study explored the feasibility of ATP-CRA as a chemosensitivity test in patients with colorectal cancer. MATERIALS AND METHODS: A total of 118 patients who underwent surgical resection for colorectal adenocarcinoma were analyzed for chemosensitivity to 6 anticancer drugs using ATP-CRA. We calculated the cell death rate (CDR) by measuring intracellular ATP levels of drug-exposed cells and untreated controls. RESULTS: Interpretable results were available for 85.5% (118/138) of patients. The mean coefficient of variation for triplicate ATP measurements was 9.2%. The highest CDR was observed in irinotecan (34.0%) and the lowest CDR in etoposide (21.0%). Paclitaxel had the broadest range of CDR (0-86.7%) and 5-FU had the narrowest range of CDR (0-56.8%). The overall highest responsiveness was seen most prevalently in irinotecan (24.7%, 23/93 patients). Irinotecan had the greatest responsiveness in patients with well differentiated and moderately differentiated carcinoma. CONCLUSION: Our study suggests that ATP-CRA could be used to identify patients with colorectal cancer who might benefit from treatment with a specific chemotherapeutic agent.

Preliminary Study of the Clinical Features of the Chemosensitivity Test in Colorectal Cancer

PURPOSE: Colorectal cancers have been known to be refractory to chemotherapy in the past decades. Recently, novel agents have been developed and various data have shown an improved response rate and a survival benefit. However, considerable heterogeneity exists between cancers of the same tissue type, including colorectal cancer. Thus, Individualized chemotherapy that is tailored specifically to the characteristics of the tumor is necessary for an improved clinical outcome. RESULTS: We evaluate the chemosensitivity of colorectal cancer to standard drugs (5-FU, oxaliplatin, and irinotecan) and to drugs used for other cancers (mitomycin, paclitaxel, and gemcitabine) by using Adenosine-triphosphate-based chemotherapy response assay (ATP-CRA). RESULTS: The degree of in-vitro response to a single anticancer medication was highest for 5-FU. According to stages, 5-FU is the most sensitive chemotherapeutic agent in Duke's B, irinotecan in Duke's C, and 5-FU in Duke's D patients. With tumor location, irinotecan is most sensitive in colon cancers and 5-FU in rectal cancers. The effect of treatment is superior in the test-guided therapy group in Duke's D colorectal cancer patients. CONCLUSIONS: Chemosensitivity tests may be useful in selecting optimum drugs for patient who require chemotherapy. However, the results of this study do not strongly support the usefulness of this assay; further studies with a sufficient number of cases and an extended observation period are ongoing.

The Results of the ATP Based Chemotherapy Response Assay in Gastric Cancer Tissues

PURPOSE: Recently, chemosensitivity tests have become widely used for the selection of effective drugs in gastric cancer patients. In this study, a chemosensitivity test was performed to select agents to increase the effectiveness of adjuvant chemotherapy. MATERIALS AND METHODS: Chemosensitivity testing was performed in 81 gastric cancer patients that received a gastrectomy at the Yeungnam University Hospital. An ATP (adenosine triphosphate) based chemotherapy response assay was used. Clinicopatholgical factors such as sex, age, expression of tumor markers (CEA and CA19-9 levels), location of the tumor, morphology of advanced cancer, histological type, cell differentiation, depth of invasion, Lauren classification, Ming classification, lymphatic invasion, vascular invasion, neural invasion, lymph node metastasis and TNM stage were used to correlate the chemosensitivity and clinicopathological factors. RESULTS: The most effective antitumor agents in gastric cancer patients were (in order of effectiveness) 5-FU, Epirubicin, Irinotecan and Oxaliplatin in our series. The chemosensitivity test showed a significant difference in susceptibility according to clinicopathological factors. CONCLUSION: Further studies on multidrug therapy are needed to evaluate synergistic effects of drugs. Therefore, for effective chemotherapy, it is more efficacious to select a chemosensitive drug than continue to use the same drug regimen.