Journal
CANCER COMMUNICATIONS
Volume 38, Issue -, Pages -Publisher
WILEY
DOI: 10.1186/s40880-018-0318-8
Keywords
Gallbladder cancer; Mini-PDX; Chemosensitivity; Overall survival; Personalized therapy
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Funding
- Foundation of Shanghai Shen Kang Hospital Development Center [16CR2002A, 16CR3028A]
- National Science Foundation of China [81472240, 81773184]
- Shanghai Outstanding Academic Leaders Plan (2016)
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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. 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 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. 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). Conclusion: The use of mini-PDX model to guide selection of chemotherapeutic regimens could improve the outcome in patients with gallbladder carcinoma.
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