To explore the clinical feasibility of the patient-derived tumor xenograft (PDTX or PDX) mouse model in guiding the individualized precise treatment of advanced digestive system tumors through a multicenter clinical study.
14 centers participated the trial in China. Fresh tumor tissues were obtained by surgery and biopsy, then engrafted subcutaneously into immune deficient mice. When the tumor volume grew to 60 mm3, the modeling was successful. The consistency of the original tissue (PA) and the engrafted tissue (P0) was analyzed by pathological comparison. The tumorigenesis time model was recorded. After successful modeling, medication was administered in groups according to the recommended regimen for 21 days. The tumor growth inhibition rate (TGI) was recorded and evaluated as positive if TGI > 60%. According to RECIST 1.1, DCR (SD, PR, CR) was evaluated as positive in clinical synchronous treatment. The two results were compared to evaluate the accuracy of guiding clinical medication.
A total of 33 patients with different advanced digestive system tumors were included, including 2 cases of esophageal cancer, 10 cases of colorectal cancer, 10 cases of pancreatic cancer, 5 cases of gastric cancer, 3 cases of liver cancer, 2 cases of duodenal adenocarcinoma and 1 case of gallbladder cancer. The successful rate of tumor xenograft modeling was 75.8% (25/33), including 78.3% (18/23) in small samples and 70% (7/10) in surgical samples. Pathological results showed that the consistency of P0 and PA was 100% in 25 cases. The average tumorigenesis time of PDTX model was 42 days. Pharmacodynamic tests were completed in 17 cases, including 28 kinds of drugs and 49 regimens. The clinical efficacy of 10 regimens in 9 patients were evaluated as PR in 2 cases, SD in 6 cases and PD in 2 cases. The results of pharmacodynamic test were consistent with clinical synchronous efficacy.
PDTX mouse model has high successful modeling rate with the biological and pathological characteristics of primary tumor, and the results of pharmacodynamic test are highly consistent with the clinical efficacy. It can be used as a individualized diagnosis and treatment technique of advanced gastrointestinal tumors.
The authors.
Nanjing Personal Oncology Biotechnology Co. Ltd.
All authors have declared no conflicts of interest.