Three-year follow-up analysis of phase 1/2 study on tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma.

Background: The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term efficacy and safety after a 3-year follow-up. Methods: Eligible patients were aged ≥ 20 years with histologically diagnosed PCNSL and KPS of ≥ 70. Patients received oral tirabrutinib once daily at 320 or 480 mg, or 480 mg under fasted conditions. Results: Between October 19, 2017, and June 13, 2019, 44 patients were enrolled: 33 and 9 had relapsed and refractory, respectively. The 320, 480, and 480 mg fasted groups included 20, 7, and 17 patients, respectively. The median follow-up was 37.1 months. The overall response rate was 63.6% (95% CI: 47.8-77.6) with complete response (CR), unconfirmed CR, and partial response in 9, 7, and 12 patients, respectively. The median duration of response (DOR) was 9.2 months, with a DOR rate of 19.8%; the median progression-free survival (PFS) and median overall survival (OS) were 2.9 months and not reached, respectively, with PFS and OS rates of 13.9% and 56.7%, respectively. Adverse events occurred in 38 patients (86.4%): grade ≥ 3 in 23 (52.3%) including 1 patient with grade 5 events. KPS and quality of life (QoL) scores were well maintained among patients receiving long-term treatment. Conclusions: The results demonstrated the long-term clinical benefit of tirabrutinib, with deep and durable response in a subset of patients and acceptable safety profile, while KPS and QoL scores were maintained.

Extracranial internal carotid artery-dissecting aneurysm having a re-entry tear and causing lower cranial nerve palsies treated with flow-diverting stent: A case report.

Background: Extracranial internal carotid artery (ICA)-dissecting aneurysms (DAs) rarely cause re-entry tears and lower cranial nerve palsies. The therapeutic strategies for these pathologies are not well established. This report presents a case of an extracranial ICA -DA with a re-entry tear that caused lower cranial nerve palsy. Case Description: A 60-year-old man presented with left neck pain, hoarseness, and dysphagia. Physical examination and laryngoscopy determined palsies of the left cranial nerves IX, X, and XII. Digital subtraction angiography (DSA) revealed a DA in the left extracranial ICA, and three-dimensional DSA showed entry and re-entry tears in the intimal flap. Flow-diverting stents (FDSs) were placed on the lesion that covered the entry and re-entry tears because the symptoms did not improve after five weeks of conservative treatment. A post-procedural angiogram indicated flow stagnation in the DA. Symptoms improved remarkably immediately after the procedure, and the aneurysm was almost completely occluded six months later. Conclusion: Herein, an extracranial ICA -DA with a re-entry tear that caused lower cranial nerve palsy did not improve after five weeks of conservative treatment. FDS placement promptly resolved the aneurysm and symptoms. Thus, FDS placement may be an effective treatment option for extracranial ICA-DAs with re-entry tears or lower cranial nerve palsies.

Treatment Outcomes in Patients with Unruptured Anterior Choroidal Artery Aneurysms: A Single-Center Experience.

Objective: Treatment of anterior choroidal artery (AChA) aneurysms is frequently associated with ischemic complications. This study aimed to report the outcomes of treatment of unruptured AChA aneurysms in our hospital. Methods: Between January 2015 and March 2022, 40 patients were treated for an unruptured AChA aneurysm in our hospital. Age, sex, aneurysm size, AChA branching type, treatment, occlusion rate, complications, modified Rankin Scale (mRS) score before surgery and after 90 days, and recurrence were investigated. The branching type was classified as internal carotid artery (ICA), neck, or dome type based on the location of the AChA origin. Results: The mean age was 61.1 ± 1.9 years; 15 patients were men and 25 were women. The mean aneurysm diameter was 4.4 ± 0.3 mm. The branching type was ICA in four patients, neck in 35, and dome in one. Treatment was surgical clipping in 22 patients and endovascular coil embolization in 18 (14 with stent assistance). Motor-evoked potential (MEP) monitoring was used in all patients of the clipping group and 9 cases of the coiling group. Treatment complications occurred in eight patients (20%). mRS score worsened by more than one point 90 days after treatment in four patients (10%); however, the proportion of patients who experienced this did not significantly differ between the clipping and coiling groups. Although the odds of a thrombotic complication were higher with coiling than clipping, the difference was not significant (odds ratio: 10.2; P = 0.08). The rate of complete occlusion was lower in the coiling group (72.2% vs. 95.3%), but the difference was not significant. The median follow-up was 696 days (range: 99-2053). No aneurysm recurrence or rupture occurred. Conclusion: AChA branching type is important for treatment decision-making in patients with AChA aneurysms. Rates of complications and occlusion do not significantly differ between clipping and coiling of AChA aneurysms. MEP monitoring may be useful in preventing thrombotic complications during coil embolization.

The Usefulness of the 3.1-mm-diameter 4K Rigid Endoscope for Intracerebral Hematoma Evacuation.

The indication for surgical intervention in spontaneous intracerebral hemorrhage remains controversial. Although many clinical trials have failed to demonstrate its efficacy over medical treatment, less invasive endoscopic treatment is expected to demonstrate its superiority. A novel endoscopic system for hematoma removal consisting of a 3.1-mm-diameter 4K high-resolution rigid endoscope was used.The system was used in eight cases of spontaneous intracerebral hemorrhage. It provided improved maneuverability of the surgical instrument while maintaining satisfactory image quality. The surgical goal was achieved in all cases without any complications, including perioperative rebleeding.Endoscopic hematoma removal using the 3.1 mm high-resolution endoscope is an alternative minimally invasive approach to spontaneous intracerebral hemorrhage with improved reliability.

Treatment Outcomes of PED for Unruptured Aneurysms of Internal Carotid Artery: Comparison of PED-Flex and PED-Shield.

There is a lack of data regarding the safety and effectiveness of implanting the Pipeline Embolization Device with Shield technology (PED-Shield) compared with the previous generation of Pipeline (PED-Flex). This retrospective single-center study aimed to compare treatment outcomes between the PED-Shield and PED-Flex for treating unruptured internal carotid artery aneurysms. The PED-Flex was used in 62 procedures (67 aneurysms, 59 patients) and the PED-Shield in 53 procedures (59 aneurysms, 58 patients). The mean aneurysm diameter was significantly lower in the PED-Shield group than in the PED-Flex group (11.9 ± 7.0 mm vs. 15.2 ± 6.9 mm, p < 0.001). At the 12-month follow-up, the complete angiographic occlusion rate was 72.1% and 72.3% in the PED-Flex and PED-Shield groups, respectively (p = 0.9808). Limited to aneurysms larger than 10 mm, 70.6% and 68.0%, respectively (p = 0.8175). The incidence of more than three high signal intensity areas on diffusion-weighted imaging after treatment was significantly lower in the PED-Shield group than in the PED-Flex group (27.7% vs. 67.7%; p < 0.001). Limited to aneurysms larger than 10 mm, 41.1% and 69.6%, respectively (p < 0.0117). Symptomatic ischemic complications occurred within 30 days of four PED-Flex procedures (6.5%) and one PED-Shield procedure (2.0%) (p = 0.2315). Limited to aneurysms larger than 10 mm, 1.8% and 3.2%, respectively (p = 0.6677). The incidence of mRS score worsening at 6 months was 3.2% and 1.9% in the PED-Flex and PED-Shield groups, respectively (p = 0.6534). The PED-Shield can achieve outcomes equivalent to or better than the PED-Flex. Further large-scale studies are warranted to confirm our findings.