Predicting chemosensitivity based on mini patient-derived xenografts in osteosarcoma patients: A retrospective study

Abstract

The survival of patients diagnosed with osteosarcoma has not improved in the past three decades because of chemoresistance. This study aimed to improve the prognosis of patients with osteosarcoma. From January 1, 2018, to June 30, 2019, a total of 14 patients with osteosarcoma were enrolled who underwent mini patient-derived xenograft (mini-PDX) assay in our hospital. We recruited 14 patients with osteosarcoma having acquirable lesions to establish PDX models and examine the sensitivity of nine drugs, including methotrexate (MTX), ifosfamide (IFO), epirubicin, and etoposide. Drug sensitivity was evaluated using the tumor relative proliferation rate (TRPR), and the patients' responses were assessed according to the RECIST 1.1 guidelines. The difference in TRPR was analyzed using a paired t-test, while progression-free survival (PFS) was analyzed using the Kaplan-Meier method. The mini-PDX results revealed that IFO had a lower tumor proliferation rate than MTX, indicating that IFO was more sensitive in patients with osteosarcoma (38.3% vs. 84.3%, P = 0.031). Thus, the regimen where IFO alternates with doxorubicin and cisplatin was recommended as adjuvant chemotherapy. MTX could replace IFO if the TRPR was better. Finally, 11 patients received adjuvant chemotherapy. A comparison of PFS revealed that sensitive patients with TRPR of <40% had a better prognosis (9.4 months vs. 3.7 months, P = 0.0324). Chemotherapy based on mini-PDX can improve the survival of patients with osteosarcoma whose TRPR was <40%, and that chemotherapy without MTX could be an alternative for osteosarcoma.