Dose intensity and clinical outcomes across age groups in high-grade osteosarcoma treated with methotrexate, adriamycin, and cisplatin therapy.

Abstract

The importance of maintaining planned dose intensity (DI) of methotrexate (MTX), adriamycin, and cisplatin (MAP) chemotherapy in high-grade osteosarcoma has been highlighted in clinical trials. However, DI is frequently reduced in routine practice, particularly in adults, and its prognostic relevance in real-world settings remains unclear. We retrospectively analysed patients with high-grade osteosarcoma treated with MAP at a single center between 2014 and 2021, stratifying patients into pediatric (PED; ≤19 years), young adult (YA; 20-39 years), and older adult (OA; ≥40 years) groups. Treatment intensity was assessed using intended dose per cycle, cumulative dose over 200 days, and relative DI. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis and Cox proportional hazards models. Among 78 patients who received MAP therapy, 51 were eligible for analysis. The 3-year PFS was 61.1% (95% CI, 45.5-73.5), with no significant difference among age groups. Higher DI was not consistently associated with improved PFS or OS; metastasis at diagnosis was the only independent prognostic factor. Treatment completion rates were similar in PED and YA patients (72% and 69%, respectively) but markedly lower in OAs (22%). Delayed MTX elimination occurred more frequently in OAs. In this real-world cohort, reductions in chemotherapy delivery-particularly in OAs-were common; however, higher DI was not consistently associated with better survival outcomes. These findings highlight the complexity of interpreting DI metrics and support age-adapted treatment considerations.