The Efficacy and Safety of Pegylated Liposomal Doxorubicin-Based Neoadjuvant Chemotherapy in Children With Osteosarcoma: A Retrospective Real-World Study.

Background: Treatment of osteosarcoma in children remains difficult. The combination of chemotherapy and surgery is the classic treatment for osteosarcoma. With the development of medicine, chemotherapy has also improved greatly. This study aimed to explore the short-term efficacy and safety of neoadjuvant chemotherapy (NAC) with a protocol of pegylated liposomal doxorubicin (PLD), high-dose methotrexate, and ifosfamide (PLDMI) in pediatric patients with osteosarcoma.

Methods: Between May 1, 2018 and May 1, 2021, 25 pediatric patients with osteosarcoma were included in this retrospective, observational study. All patients received PLDMI including PLD, high-dose methotrexate, and ifosfamide, followed by surgery and postoperative chemotherapy. Tumor parameters at the time of preoperative chemotherapy were evaluated by the investigator using MRI, and the response to preoperative chemotherapy was scored according to the Huvos grading system. Short-term survival was analyzed by a Cox proportional hazard model. Safety was assessed as adverse events (AEs) by the Common Terminology Criteria for AEs version 5.0.

Results: MRI showed that preoperative chemotherapy significantly decreased the coronal tumor width, sagittal anteroposterior diameter, and tumor volume (all  < 0.05), while no significant change was found in tumor length ( > 0.05). More than 90% of tumor necrosis was achieved in 13 (61.9%, 13/21) patients. The 2-year overall survival and disease-free survival rates were 92% and 76%, respectively. Cox regression analysis identified pathological type and imaging at the time of completion of treatment as independent prognostic factors for children with osteosarcoma. Grade 3-4 AEs included febrile neutropenia (25/25, 100%), secondary anemia (18/25, 72%), secondary thrombocytopenia (20/25, 80%), and mucositis with local infection (3/25, 12%), which were resolved with symptomatic treatment.

Conclusions: PLDMI was an effective protocol for children with osteosarcoma and could effectively reduce the tumor burden in the primary site and augment surgical treatment, although with a high incidence of AEs.