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In vitro high-throughput drug sensitivity screening with patient-derived primary cells as a guide for clinical practice in hepatocellular carcinoma—A retrospective evaluation - 11/10/20

Doi : 10.1016/j.clinre.2020.01.003 
Jinghe Li a, Xiu Xiong b, Zuo Wang a, Yufei Zhao a, Zhengrong Shi a, ⁎ , Ming Zhao c, Tao Ren c
a Department of Hepatobiliary surgery, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China 
b Digestive Center, University-Town Hospital of Chongqing Medical University, Chongqing, China 
c Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China 

⁎Corresponding author.

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Highlights

•
Adjuvant chemotherapy is a useful postoperative treatment method for patients with hepatocellular carcinoma.
•
Accurate individualized treatment of tumor patients is a positive treatment.
•
The first generation of cells cultured from patients’ post-operative specimens for drug sensitivity can avoid the cell mutations caused by repeated culture.
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High-throughput drug sensitivity screening can be a new method for determining drug sensitivity for hepatocellular carcinoma.

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Summary

Aim

The aim of the study was to determine the clinical value of in vitro high-throughput drug sensitivity screening with primary hepatocellular carcinoma cells to select drugs for adjuvant chemotherapy.

Methods

This study included 162 patients who underwent hepatectomy from September 2013 to December 2016. The patients were divided into a drug sensitivity screening group and an empirical treatment group. High-throughput drug sensitivity screening using primary HCC cells was carried out and, based on the test results, effective drugs were selected for treatment. Patients in the empirical group were treated with commonly used drugs, according to the clinicians’ preferences. Clinical efficacy, i.e., disease-free survival (DFS) time, was compared between the two groups.

Results

Most patients with HCC showed extensive resistance to known chemotherapeutic drugs. However, bortezomib, regorafenib, sorafenib, romidepsin, hydroxycamptothecin and adriamycin+oxaliplatin showed strong anti-HCC activity in the sensitivity assay. Comparing clinical efficacy, the overall median DFS of patients in the drug sensitivity screening group was significantly better than that of patients in the empirical treatment group (17.00±3.80 months vs. 9.00±1.18 months, P=0.001). Median DFS times in the TACE group were 9.00±4.07 months vs. 7.00±1.06 months (P=0.014) and median DFS times in the oral drugs group were 16.80±3.98 months vs. 10.00±0.81 months (P=0.024). Patients DFS was 69.4%, 62.5% at 1-, 2- years, respectively, for patients with drug sensitivity screening, and 48.5%, 37.8% at 1-, 2- years, respectively, for patients with empirical treatment.

Conclusion

High-throughput drug sensitivity screening can be successfully used to screen chemotherapeutic drugs for efficacy against HCC and the efficacious drugs can be used in postoperative adjuvant chemotherapy of HCC patients. This treatment paradigm is safe and reliable, and improves survival compared with empirical chemotherapy.

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Keywords : High-throughput drug sensitivity screening, Primary hepatocellular carcinoma, Adjuvant chemotherapy


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Vol 44 - N° 5

P. 699-710 - ottobre 2020 Ritorno al numero
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