The influence of radiation treatment options on the urokinase system of plasminogen activation in the blood of patients with metastatic brain lesions

Purpose of the study. To investigate the effects of different radiotherapeutic modalities on parameters of the urokinase-type plasminogen activation system of fibrinolysis in the blood of patients with metastatic brain tumors (MBT).

Patients and methods. According to treatment modality, 38 patients with MBT were divided into three groups: the control group received stereotactic radiotherapy to the bed of the resected metastasis with a single focal dose (SFD) of 6 Gy to a total dose of 30 Gy; the comparison group underwent a session of preoperative radiosurgery with an SFD of 10–15 Gy followed by surgical resection of the metastatic lesion 24 h later; the main group received staged radiosurgery (SRS) in three stages with an SFD of 10 Gy and 14‑day intervals between sessions (total dose, 30 Gy). The activity and concentration of urokinase-type plasminogen activator (uPA) and the level of its cellular receptor (uPAR) were measured in blood plasma. The results were compared with those obtained from 18 donors without malignant disease.

Results. Before treatment, patients demonstrated a 3.6‑fold decrease in plasma uPA concentration and a 1.8‑fold decrease in uPAR levels compared with donors (p < 0.0001), which was accompanied by a more than twofold reduction in the activity and concentration of plasminogen activator inhibitor type 1 (PAI‑1). An increase in uPA activity and concentration during treatment was observed only in the SRS group; as a result, one month after treatment, uPA activity was 2.7‑fold higher than in the control group (p < 0.0001), and uPA concentration was 1.2‑fold higher than in the comparison group (p = 0.031), which was accompanied by normalization of uPAR levels.

Normalization of PAI‑1 activity immediately after treatment and one month later was observed only in the main group, while its concentration remained stable. In contrast, the control group exhibited a decrease in PAI‑1 concentration, whereas the comparison group showed an increase in PAI‑1 concentration with a loss of activity on postoperative day 3. In the control group, a pronounced imbalance of the urokinase system was observed, as evidenced by the calculated uPA/uPAR ratios.

Conclusion. The observed differences in the direction of changes in the components of the urokinase system under different radiotherapy modalities are consistent with the superior clinical effectiveness of the developed and patented SRS method in the treatment of patients with MBT.

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