Periprosthetic seromas and a third space effect after high-dose methotrexate

Area of Science:

• Oncology
• Pharmacology
• Biomedical Engineering

Background:

• High-dose methotrexate (HDMTX) is a primary chemotherapy for osteosarcoma.
• Methotrexate can accumulate in "third spaces" like periprosthetic seromas, leading to local toxicity and delayed drug elimination.
• The study investigates the potential toxic risk associated with methotrexate accumulation in periprosthetic seromas.

Purpose of the Study:

• To compare methotrexate concentrations in serum and periprosthetic seromas.
• To evaluate the potential toxic risk of the "third space effect" in osteosarcoma patients treated with HDMTX.
• To determine if periprosthetic seroma fluid analysis is necessary.

Main Methods:

• Retrospective analysis of methotrexate concentrations in serum and periprosthetic seromas from 45 osteosarcoma patients treated with endoprosthesis and HDMTX (1991-2011).
• 112 periprosthetic seroma aspirations were performed in 18 patients.
• Wilcoxon test was used to assess differences in concentrations.

Main Results:

• Periprosthetic seroma methotrexate concentrations were significantly higher than serum concentrations at 24, 48, and 72 hours post-treatment (median 14.86-fold, 8.50-fold, and 2.66-fold, respectively).
• Highly toxic methotrexate concentrations (≥20 μmol/l) were observed in 30% of analyzed seromas at 24 hours.
• Patients with prior seroma puncture showed significantly higher serum concentrations at 45 hours.

Conclusions:

• Methotrexate concentrations in periprosthetic seromas are substantially higher than in serum, indicating a potential "third space" toxicity risk.
• Puncturing these seromas may be necessary to mitigate severe adverse effects.
• Further research into managing methotrexate accumulation in seromas is warranted.