2025 Background: Metastatic brain disease (MBD) is found in almost a third of patients with malignant neoplasms and is characterized by a high mortality rate. The role of the fibrinolytic system has been demonstrated in neoplasms of various locations, while tissue plasminogen activator (t-PA) is studied less frequently than urokinase activator. The aim of this study was to investigate the level and activity of t-PA in the blood of patients with MBD receiving different radiotherapeutic treatments. Methods: Plasma from 38 patients of both sexes, aged 59.9 ± 8.9 years, with brain metastases confirmed by magnetic resonance imaging (MRI), was analyzed using enzyme-linked immunosorbent assay (ELISA) to determine t-PA activity and levels, calculate the ratio between them, and determine parameters of type 1 plasminogen activator inhibitor (PAI-1) and the receptor for both plasminogen activators (uPAR). The results were compared with data from 18 individuals without cancer (a donor group). Three groups were formed based on the treatment regimens: Control — stereotactic radiotherapy at the site of the resected metastasis with a single fraction dose (SFD) of 6 Gy up to a total dose of 30 Gy; Main Group No. 1 — after a preoperative radiosurgery session with an SFD of 10–15 Gy, the metastatic lesion was removed 24 hours later; Main Group No. 2 — staged radiosurgery (SRS) was performed in 3 sessions with an SFD of 10 Gy at 14-day intervals (total dose of 30 Gy). Results: Before treatment, a 2.1-fold increase in t-PA activity was observed in the blood of patients with MBD. This, together with a 3.6-fold reduction in t-PA content, led to a 10-fold increase in their ratio (p ≤ 0.0002). Meanwhile, urokinase activator activity did not change. In the control group, t-PA activity remained elevated three days after surgery and did not differ from donor levels one month later, while t-PA levels remained reduced. In both main groups, elevated t-PA activity relative to donors was observed throughout the entire observation period, and after one month, it was 2.6 times higher than in the control group (p ≤ 0.001). Only patients receiving SRS were characterized by an increase in the initially reduced t-PA content, with a change toward normalization of the t-PA activity-to-content ratio. This was accompanied by an increase in the activity of inhibitor PAI-1 and receptor uPAR to donor levels. Conclusions: The revealed dynamics of t-PA and PAI-1 parameters in SRS compared with other types of radiation therapy may be one of the factors contributing to the greater positive clinical efficacy of this developed method of staged radiotherapy in the treatment of metastatic brain tumors.
Goroshinskaya et al. (2026) studied this question.