Multimodality, aggressive and sustainable care in metastatic osteosarcoma: A tertiary care cancer experience from India

Abstract

Background: Metastatic osteosarcoma outcomes are dismal, despite costly and complex high-dose methotrexate (HDMTX)-based therapies. This is challenging especially in lower and middle-income countries (LMICs) with limited resources & increasing patient volumes. We need to reallocate resources to efficient but sustainable strategies, like exploring Non-HDMTX based protocols and aggressive multimodality approach in this setting. Methods: All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the “OGS-12” protocol, which involved administration of eight sequential doublets of the three most active drugs (doxorubicin, cisplatin, and ifosfamide), universal growth factor prophylaxis and targeted nutritional support if required. Four cycles were administered as neoadjuvant therapy (NACT) followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy (ACT). Results: Four ninety-five patients were enrolled in the OGS-12 protocol from 2011 to 2016, of whom 110 (22%) had metastatic disease; the median age was 17 years. The majority of patients were nutritionally challenged with high-risk features like high LDH (80%), high SAP (91%). After NACT, 57% of patients were histologically good responders (gHR) that is ≥ 90% tumor necrosis. Five-year event-free survival (EFS) & overall survival(OS) rates were 24% & 20%, respectively, in the intent-to-treat and 43% & 29%, respectively, in the perprotocol populations. Significant grade 3/4 toxicities were febrile neutropenia (29%), thrombocytopenia (39%), and anemia (56%). Ability to perform metastectomy for improved OS, compliance to therapy for improved EFS, and gHR for both improved EFS and OS were identified as independent prognostic markers. Conclusions: Adoption of an aggressive multimodality approach including the novel, lowcost, Non-HDMTX-based, dose-dense “OGS-12” protocol, enhanced supportive care & compliance, with metastectomy resulted in internationally comparable outcomes of metastatic osteosarcoma patients. This rational and sustainable, economically efficient strategy is worthy of wide adaption.