Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

Abstract

Abstract. Using trace three-dimensional culture, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) can be tested even in cases with a small number of cells, including oral squamous cell carcinoma (OSCC), and evaluation of the antitumor effect with a drug concentration close to the in vivo level is possible. The present report aimed to evaluate the utility of the CD-DST in the assessment of the in vitro efficacy of single-agent and multidrug combination chemotherapy for OSCC in comparison with the clinical response rates and to examine the possible clinical application of CD-DST for such cases. A total of 33 OSCC patients from whom 33 samples were obtained from January 2010 to September 2015 were included. CD-DST was performed, individually and in combination, on the three drugs [i.e., cisplatin (CDDP), 5-fluorouracil (5-FU), and docetaxel (DOC)] and on super selective intra-arterial infusion chemoradiotherapy (IACRT). The overall evaluable rate of the CD-DST in OSCC was 81.8% (27 of 33 cases) and the sensitivity to each anticancer drug was evaluated. The in vitro efficacy rates of IACRT, cisplatin + 5-fluorouracil, and docetaxel + cisplatin + 5-fluorouracil (TPF) confirmed the estimated clinical response rates. In 14 of 33 patients, the results of CD-DST were compared with clinical efficacy, which was judged based on measurable lesions on imaging. For TPF therapy, the sensitivity test of the IACRT had a positive predictive value of 90.9% (10 of 11 cases) and a negative predictive value of 100% (3 of 3 cases); the accuracy of the susceptibility test for the anticancer agents was 92.8% (13 of 14 cases). The CD-DST may be useful in selecting multidrug combination chemotherapy and IACRT for OSCC, however, accumulation of further clinical data is required in the future. IntroductionThe treatment of advanced or unresectable oral squamous cell carcinoma (OSCC) is multidisciplinary and entails the use of both multidrug combination chemotherapy and radiotherapy (1-3). The usefulness of super selective intraarterial infusion chemoradiotherapy (IACRT) to deliver high concentrations of anticancer drugs to tumors has been reported (4). The selection of such anticancer drugs for IACRT had been based on statistical information and clinical reports on a number of cases (1-3); however, the expected therapeutic effects of these anticancer drugs have not been consistent and adverse events were common. Therefore, drug sensitivity testing prior to administration of an anticancer agent is ideal to avoid the serious side effects of less effective anticancer drugs. Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) uses an image colorimetric method to assess the combination of an anticancer drug and microcollagen gel embedded in a three-dimensional serum-free culture medium (3 to 10x10 3 cells/30 µg/drop) (5,6). It is a susceptibility test that is currently widely applied in various clinical fields, including gastrointestinal cancer (7-9). However, reports on the use of CD-DST in OSCC were few a...

Identification of the optimal cetuximab concentration that is effective against oral squamous cell carcinoma in collagen gel droplet embedded culture drug sensitivity testing

“…In fact, the primary measurement success rate of the CD-DST was reported to be 87.5% in colorectal cancer, 79.2% in lung cancer, and 84.3% in breast cancer (16)(17)(18), and it shows a high clinical efficacy prediction rate of 91% (5). Similarly, in sensitivity testing using cisplatin, fluorouracil, or docetaxel in OSCC, as we reported earlier, the primary culture success rate was 81.8% (19). In the present study, we conducted anticancer drug sensitivity testing, including cetuximab specimens of OSCC cases, with a success rate of 83.3% (20 of 25 cases) in primary tumors, 100% (1 out of 1 case) in metastatic lymph nodes, and 84.0% overall (21 of 25 cases).…”

Optimal Contact Concentration of Paclitaxel in the Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test for Human Oral Squamous Cell Carcinoma and Evaluation of Combination with Cetuximab

“…In fact, the reported measurement success rates of CD-DST were 87.5% for colorectal cancer, 79.2% for lung cancer, and 84.3% for breast cancer [24][25][26], with a predicted clinical effect rate of 91% [11]. Similarly, as previously reported, sensitivity tests using cisplatin, fluorouracil, or docetaxel for OSCC showed a success rate of 81.8% in primary cultures, with a clinical predictive value of 92.8% [14]. In addition, anticancer drug susceptibility tests, including those of cetuximab-associated samples from patients with OSCC, were performed with success rates of 83.3% for primary tumors, 100% for metastatic lymph nodes, and 84.0% overall [15].…”

“…The collagen gel droplet-embedded culture drug sensitivity test (CD-DST), which was developed by Kobayashi et al [11], is an anticancer drug sensitivity test that combines three-dimensional (3D) microcarrier cell culture with serum-free medium and image-based colorimetric analysis [11]. This method has demonstrated high success rates for a wide range of diseases, including OSCC, by overcoming many the limitations of conven-tional chemosensitivity tests [12][13][14][15]. Because CD-DST uses a micro-3D culture, it can be used to evaluate OSCC and other cancers that have low tumor volume.…”

Establishment and Characterization of the Human Tongue Squamous Cell Carcinoma Cell Line NOKT-1

“…Previous reports have shown that CD-DST has a clinically successful measurement rate of 87.5% in colorectal cancer, 79.2% in lung cancer, and 84.3% in breast cancer [17][18][19] . Similarly, as previously reported, sensitivity tests using cisplatin, fluorouracil, or docetaxel at OSCC showed a success rate of 81.8% in primary culture 15) . In addition, we conducted anticancer drug susceptibility tests, including those for cetuximab, using OSCC samples with success rates of 83.3% for primary tumors, 100% for metastatic lymph nodes, and 84.0% overall 16) .…”

“…This method has advantages in that it allows testing using smaller quantities of cells compared with conventional assays. Furthermore, it eliminates the effects of fibroblasts that can adulterate samples at the time of harvesting and allows the evaluation of physiological drug concentrations [13][14][15][16] . In addition, the CD-DST method can be evaluated by combining multiple anticancer agents.…”