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

基于患者微异种移植模型的指导化疗可提高胆囊癌患者的生存率

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作者:Ming Zhan, Rui-Meng Yang, Hui Wang, Min He, Wei Chen, Sun-Wang Xu, Lin-Hua Yang, Qiang Liu, Man-Mei Long, Jian Wang

Background

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.

Conclusion

The use of mini-PDX model to guide selection of chemotherapeutic regimens could improve the outcome in patients with gallbladder carcinoma.

Methods

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

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).

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