Guided chemotherapy based on patient-derived mini-xenograft models improves survival of gallbladder carcinoma patients

Cancer Communications

Hui Wang¹  Min He¹  Sun-wang Xu¹  Ming Zhan¹  Wei Chen¹  Rui-meng Yang¹  Lin-hua Yang¹  Qiang Liu²  Man-mei Long³  Jian Wang⁴ 

[1]Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China

[2]Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China

[3]Department of Pathology, Shanghai Ninth People’

[4]s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China

关键词: Gallbladder cancer;    Mini-PDX;    Chemosensitivity;    Overall survival;    Personalized therapy;   

DOI  :  10.1186/s40880-018-0318-8

学科分类：肿瘤学

来源: Springer

【 摘 要 】

Gallbladder carcinoma is highly aggressive and resistant to chemotherapy, with no consistent strategy to guide first line chemotherapy. However, patient-derived xenograft (PDX) model has been increasingly used as an effective model for in preclinical study of chemosensitivity. Mini-PDX model was established using freshly resected primary lesions from 12 patients with gallbladder to examine the sensitivity with five of the most commonly used chemotherapeutic agents, namely gemcitabine, oxaliplatin, 5-fluorouracil, nanoparticle albumin-bound (nab)-paclitaxel, and irinotecan. The results were used to guide the selection of chemotherapeutic agents for adjunctive treatment after the surgery. Kaplan–Meier method was used to compare overall survival (OS) and disease free survival (DFS) with 45 patients who received conventional chemotherapy with gemcitabine and oxaliplatin. Cell viability assays based on mini-PDX model revealed significant heterogeneities in drug responsiveness. Kaplan–Meier analysis showed that patients in the PDX-guided chemotherapy group had significantly longer median OS (18.6 months; 95% CI 15.9–21.3 months) than patients in the conventional chemotherapy group (13.9 months; 95% CI 11.7–16.2 months) (P = 0.030; HR 3.18; 95% CI 1.47–6.91). Patients in the PDX-guided chemotherapy group also had significantly longer median DFS (17.6 months; 95% CI 14.5–20.6 months) than patients in the conventional chemotherapy group (12.0 months; 95% CI 9.7–14.4 months) (P = 0.014; HR 3.37; 95% CI 1.67–6.79). The use of mini-PDX model to guide selection of chemotherapeutic regimens could improve the outcome in patients with gallbladder carcinoma.

【 授权许可】

CC BY