Beijing Tiantan Hospital Affiliated to Capital Medical University

Tenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. Moreover, its high specificity for fibrin may contribute to a reduction in haemorrhage complications. However, the safety, tolerability and efficacy of TNK, combined with neuronavigation-assisted stereotactic minimally invasive puncture, in patients with acute spontaneous deep cerebral haemorrhage remain unknown.

We conducted a prospective, open-label phase I trial in a 3+3 dose escalation design to evaluate the safety and tolerability, and maximum tolerated dose (MTD) of TNK in patients with acute spontaneous basal ganglia or thalamic haemorrhage, with haematoma volumes ranging from 20 to 50 mL, combined with neuronavigation-assisted stereotactic minimally invasive puncture surgery (MIPS). During the dose-escalation phases of the trial, patients received intra-haematoma injection of TNK via a haematoma evacuation catheter every 24 hours after surgery until three doses were administered or any termination criteria were met (residual haematoma ≤10 mL or rebleeding event), with doses ranging from 0.001 to 0.003 and 0.009 mg per mL of haematoma volume. The primary safety endpoint was drug-related rebleeding during the dose escalation phases, while the primary efficacy endpoint was the mean drug-related haematoma clearance per dose.

In total, 12 patients were recruited. No drug-related rebleeding events at any dose escalation phase occurred. By the 24 hours after the last dose, the residual haematoma volume for each patient across all groups was reduced to less than 10 mL. The 0.009 mg TNK dose group achieved the highest mean haematoma clearance of 17.49 mL per dosing. The MTD was 0.009 mg/mL of haematoma volume in the dose escalation phase.

TNK is well tolerated with encouraging signs of dissolving blood clots. Further exploration of TNK combined with neuronavigation-assisted stereotactic MIPS in patients with acute spontaneous deep cerebral haemorrhage is warranted.

NCT06668441 .

Leptomeningeal metastases (LM) in epidermal growth factor receptor mutant (EGFRm) non-small-cell lung cancer (NSCLC) represent a major therapeutic challenge. Despite the improved central nervous system penetration of third-generation EGFR tyrosine kinase inhibitors (TKIs), key uncertainties persist regarding the efficacy of combination regimens with antiangiogenic therapy and intrathecal chemotherapy and optimal dosing because of the limited evidence.

In this large-scale, multicenter, retrospective study, 618 patients with EGFRm NSCLC and LM who were treated with furmonertinib-based regimens between March 2021 and December 2024 were enrolled. The primary endpoint was overall survival (OS). Secondary endpoints included OS from LM diagnosis (LMOS), time to treatment failure (TTF), clinical response rate (CRR), LM-specific objective response rate (ORR-LM), and treatment-related adverse events (TRAEs).

The median OS was 14.19 months [95% confidence interval (CI) 13.04-16.79], median LMOS was 17.05 months (95% CI 14.81-19.22), and median TTF was 11.23 months (95% CI 10.23-12.13). Triple therapy (furmonertinib plus antiangiogenic therapy and chemotherapy) was associated with longer median OS than mono or dual regimens (17.91 versus 10.31-14.19 months, P < 0.001). Notably, among patients with prior third-generation EGFR-TKI exposure, triplet therapy achieved a median OS of 17.18 months. In patients with poor performance status (Eastern Cooperative Oncology Group score 3-4), triplet therapy showed markedly improved OS compared with other regimens (17.31 versus 9.02-12.81 months, P = 0.003). Regarding furmonertinib dosing, 80 mg/day and 160 mg/day were associated with longer OS than 240 mg/day (16.79/14.68 versus 11.39 months, P = 0.002). The CRR was 66.7%, and the ORR-LM was 40.6%. TRAEs occurred in 59.2% of patients, with grade 3-4 events reported in 7.9%.

This large real-world study suggests that furmonertinib-based therapy, particularly the triplet regimen with antiangiogenic agent and chemotherapy, is associated with meaningful clinical outcomes over mono or dual therapy in patients with EGFRm NSCLC and LM, including those with prior third-generation TKI resistance or poor performance status.

The optimal selection of stent size remains uncertain. This study evaluated the impact of stent diameter on in-stent stenosis (ISS) after interventional therapy through a subgroup analysis of the Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter (IMPACT) trial.

This prospective, multicenter study included patients treated with the Tubridge Flow Diverter (TFD) at 14 centers between December 16, 2019 and October 26, 2022. The primary outcome was the incidence of ISS at the 12-month follow-up. We analyzed the effect of different stent sizes on ISS in all patients from IMPACT who had follow-up imaging. The parent artery was divided into proximal and distal vessels, and we introduced the ratio of diameter (RD) as a parameter to assess the association between stent diameter and vessel diameter.

A total of 167 patients with 195 intracranial aneurysms were included. ISS was classified as mild (<25%) in 9 cases (5.4%), moderate (25–50%) in 4 cases (2.4%), severe (51–75%) in 1 case (0.6%), and extremely severe (>75%) in 5 cases (3%). A total of 390 proximal and distal vessels were evaluated, with a mean RD of 1.14±0.26. Smaller parent artery diameter and higher RD were significantly associated with ISS (p=0.002 and p=0.021, respectively). Additionally, the risk of ISS increased when RD>1.1 (p=0.006).

In TFD treatment for intracranial aneurysms, stent size and the diameters of proximal and distal parent arteries should be carefully considered, especially in cases involving small parent arteries. Maintaining an RD of less than 1.1 may reduce the risk of ISS.