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PURPOSE In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients. METHODS Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (≥1 of the following criteria: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; ≥3 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months. RESULTS Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3% v 8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9% v 5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6.7% v 6.6%, adjusted HR, 0.95 [95% CI, 0.62 to 1.44]). CONCLUSION To our knowledge, this is the largest international comparative data set of patients with LBCL with UHR features showing no significant reduction in CNS relapse with HD-MTX in all UHR or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.

LBA7000 Background: ~40% of DLBCL pts are not cured with first-line (1L) R-CHOP, underscoring a significant unmet need for more effective 1L regimens. Tafa (anti-CD19 mAb) + Len-R-CHOP in the phase 1b First-MIND study demonstrated safety and efficacy in pts with newly diagnosed disease. frontMIND, a phase 3, double-blind, placebo-controlled study, compared Tafa-Len-R-CHOP vs R-CHOP in pts with high-risk aggressive BCLs. Methods: Pts aged 18–80 y with newly diagnosed, high-intermediate/high-risk DLBCL or HGBL (IPI 3–5, aaIPI 2–3 if ≤60 y) and ECOG PS 0–2 were randomized 1:1 to Tafa-Len-R-CHOP or R-CHOP. Primary endpoint was investigator-assessed PFS; secondary endpoints included: EFS, OS, CR, ORR, safety. Results: At primary analysis (data cutoff Oct 20, 2025), 899 pts were randomized to Tafa-Len-R-CHOP (n=448) or R-CHOP (n=451); baseline characteristics were similar between arms. With a median follow-up of 35.2 mo, Tafa-Len-R-CHOP achieved a statistically significant improvement in PFS vs R-CHOP (HR 0.75 [95% CI: 0.59, 0.96]; P =0.019) in the overall population; in pts with centrally confirmed lymphoma subtypes (n=773), PFS HR was 0.68 (95% CI: 0.52, 0.88) and 24-mo PFS was 72.7% vs 62.2%. PFS benefit was observed with Tafa-Len-R-CHOP in both molecular COO subtypes, ABC and GCB (data will be presented). Tafa-Len-R-CHOP significantly improved EFS vs R-CHOP; CR and ORR were similar between arms and HR for OS was 0.85 (final OS planned at 5y) (Table). Any-grade TEAEs were similar in treatment arms (98.6% vs 97.1%); more grade ≥3 TEAEs occurred with Tafa-Len-R-CHOP vs R-CHOP (86.7% vs 76.1%). Discontinuations due to TEAEs occurred in 25.7% vs 17.9% and deaths due to TEAEs in 5.9% vs 3.8% of pts for Tafa-Len-R-CHOP vs R-CHOP. Overall, there were fewer deaths with Tafa-Len-R-CHOP vs R-CHOP (18.5% vs 21.7%). Conclusions: The primary endpoint of frontMIND was met; Tafa-Len-R-CHOP resulted in a significant 25% reduction in risk of disease progression or death compared with R-CHOP, with an 8.2% difference in 24-month PFS rate in the overall population and 10.5% difference in pts with centrally confirmed lymphoma subtypes. TEAEs were manageable and consistent with the expected safety profile. Tafa-Len-R-CHOP represents a potential new 1L standard of care for pts with both COO subtypes of high-risk DLBCL or HGBL. Clinical trial information: NCT04824092 . Efficacy outcomes by treatment arm.* Variable Tafa-Len-R-CHOP(n=448) R-CHOP(n=451) HR or OR(95% CI) P value PFS, # events (%) † 121 (27.0) 155 (34.4) 0.75 (0.59, 0.96) 0.019 PFS rate at 24 mo, % 71.1 62.9 − − PFS rate at 36 mo, % 67.3 60.7 − − EFS, # events (%) 154 (34.4) 191 (42.4) 0.79 (0.64, 0.97) 0.026 OS, # events (%) 82 (18.3) 95 (21.1) 0.85 (0.63, 1.14) 0.270 CR at EOT, n (%) 292 (65.2) 294 (65.2) 0.998 (0.76, 1.31) 0.987 ‡ ORR at EOT, n (%) 360 (80.4) 343 (76.1) 1.290 (0.94, 1.78) 0.120 ‡ *Investigator-assessed. † Progressive disease or death from any cause. ‡ Nominal P value.

BACKGROUND: Hemorrhagic risk in dural arteriovenous fistulas (dAVFs) is largely determined by venous anatomy, but the contribution of systemic cardiovascular factors and their medical therapy remains poorly defined. This study examined associations between cardiovascular risk factors and antithrombotic use and hemorrhagic presentation, angiographic obliteration, and early functional outcomes after treatment. METHODS: We analyzed 1350 adults with intracranial dAVFs from the international Consortium for Dural Arteriovenous Fistula Outcomes Research registry, which retrospectively accrued cases across 14 centers in 4 countries between 1990 and 2017. Demographics, cardiovascular comorbidities, antithrombotic use, angioarchitectural features, treatment strategies, and follow-up outcomes were collected from prospectively maintained databases. Primary end points were hemorrhagic presentation, angiographic obliteration, and 90-day functional status after treatment. Univariable and multivariable logistic regressions were performed with model-specific adjustments. RESULTS: Hemorrhage occurred in 375 patients (27.8%) and was most strongly associated with high-grade dAVF classification and male sex; antithrombotic therapy was associated with lower odds of hemorrhagic presentation. Other cardiovascular risk factors showed no independent relationship with bleeding. Angiographic obliteration was achieved in 621 of 845 patients (73.5%). Hemorrhagic onset, high dAVF grade, and surgical treatment were independently associated with angiographic obliteration, whereas smoking and embolization demonstrated only nonsignificant trends after adjustment. At 90 days, 934 patients (88.9%) were functionally independent. Baseline modified Rankin Scale score was the strongest factor associated with 90-day functional outcome, while neither cardiovascular comorbidities nor treatment modality independently influenced functional status. CONCLUSIONS: In this large multicenter dAVF cohort, hemorrhagic presentation was most strongly associated with venous angioarchitecture. Male sex and antithrombotic therapy were also independently associated with hemorrhagic presentation. Angiographic obliteration was common, particularly among surgically treated lesions, and 90-day functional outcome was most strongly associated with baseline functional status.

This study evaluated the effectiveness of using a traditional computed tomography (CT) simulation scan in the Leksell Gamma Knife® Icon™ workflow for stereotactic radiosurgery. We compared two workflows, one involving a traditional CT simulation co-registered with the magnetic resonance imaging (MRI) and cone-beam CT (CBCT) (MRI-CT-CBCT) and another without the CT scan, co-registering the MRI directly with CBCT (MRI-CBCT). The cohort included 50 frame-based (54 targets) and 55 frameless (124 targets) patients treated between August 2020 and December 2022. Target coverage was assessed by the percentage of each target covered by the prescription isodose line. The mean coverage differences for the frame-based and frameless cohorts were −1.20% ± 1.43% and −1.06% ± 1.51%, respectively, with 95% confidence intervals of −1.59, −0.81 and −1.32, −0.79. The MRI-CBCT workflow was deemed noninferior to the MRI-CT-CBCT workflow. Our data indicate that both workflows yield similar results, suggesting that a traditional CT simulation scan is unnecessary.

Introduction Infectious intracranial aneurysms (IIAs) are rare but serious complications of systemic infections, particularly infective endocarditis. These aneurysms are prone to rupture, leading to significant morbidity and mortality. Management strategies lack consensus due to the rarity of the condition and reliance on small case series. This study examines the clinical management of IIAs using data from a large multicenter cohort. Methods A retrospective registry-based cohort study was conducted across 11 tertiary care centers in the USA between 2018 and 2023. Patients with IIAs were identified based on clinical and radiographic criteria. The primary outcome was treatment failure defined as persistence, growth, or rupture of the aneurysm. Secondary outcomes were mortality and the modified Rankin Scale (mRS) score at 90 days and 1 year. Multivariate logistic regressions were used to identify outcome predictors. Results A total of 104 patients with 166 aneurysms were included, with a median age of 43 years. Medical management was successful in 56% of cases, with failure often within 18 days of initiation. Predictors of failure included younger age, larger aneurysm size, and rupture at presentation. Surgical and endovascular interventions achieved higher success rates with better outcomes. At 90 days, 57% of patients achieved functional independence (mRS 0–2), while the mortality rate was 24%. Conclusion This study highlights the limitations of medical management for IIAs and underscores the need for early surgical or endovascular intervention in high-risk patients. Outcome predictors aid clinical decision-making, optimizing patient management. Further research is needed to standardize management guidelines for IIAs.

Background: Epcoritamab (epcor) is a first-in-class CD3xCD20 bispecific antibody (bsAb) approved for the treatment of 3L+ LBCL and follicular lymphoma. In the single-arm, phase 1/2, EPCORE NHL-1 trial (NCT03625037), epcor given until disease progression or unacceptable toxicity, demonstrated deep and durable responses, a median overall survival (OS) of 18.5 months, and a manageable safety profile in R/R LBCL. A second CD3xCD20 bsAb given as fixed-treatment duration, glofitamab (glofit), also demonstrated durable responses, conferring a median OS of 11.5 months in the pivotal study. Understanding how long-term outcomes compare among bsAb agents remains an important knowledge gap. With over 2 years of follow-up, in the absence of a head-to-head study, it is now relevant to compare the efficacy of these agents via indirect comparison. This study evaluated OS, progression-free survival (PFS), and duration of complete response (DoCR) of epcor vs glofit in R/R LBCL using data from the respective pivotal trials. Methods: Two analyses were conducted to compare the efficacy of epcor and glofit. First, a matching-adjusted indirect treatment comparison (MAIC) was conducted using published OS and PFS data from the full cohort of the glofit pivotal trial (12.6 months of follow-up, Dickinson et al, 2022) and the epcor pivotal trial (EPCORE NHL-1). Piece-wise hazard ratios (HRs) were calculated when proportional hazards assumptions were not met. Baseline characteristic prognostic variables were selected based on literature, clinical judgement, and empirical statistical testing and were adjusted between epcor and glofit cohorts. Second, in sensitivity analyses, indirect comparisons were conducted using an updated analysis of glofit with longer follow-up that included DoCR, together with OS and PFS data starting at cycle (C) 3 with 32 months of follow-up (Hutchings et al, ASH 2023). Sensitivity analyses with longer follow-up could not be adjusted because glofit pt baseline characteristics were not presented. Aggregate OS and PFS curves for glofit were derived from subgroups of pts with complete response/partial response/no response (CR/PR/NR) at C3 (Hutchings et al, ASH 2023). Aggregate epcor OS and PFS curves were similarly derived for pts with CR/PR/NR at C3 without prior disease progression. Weighted Cox proportional-hazards models were used to estimate the OS and PFS HRs between the 2 comparators. The DoCR comparison included all glofit and epcor pts achieving CR. All comparisons used EPCORE NHL-1 data with a median of 37.1 months of follow-up. Results: Pts enrolled into the pivotal trials of epcor and glofit were comparable by several key baseline characteristics before adjustment: age ≥65 y; male gender; Ann Arbor disease stage III-IV; primary refractory disease; refractory to most recent anti-CD20 therapy; previous chimeric antigen receptor T-cell therapy (CAR T); refractory to CAR T; and previous autologous stem cell transplant (ASCT). MAIC analysis revealed no significant difference in OS benefit from C1 until month 6 (HR 1.08, 95% CI 0.71, 1.64; P=0.72), but a demonstrable OS advantage from 6 months onward (HR 0.60, 95% CI 0.37, 0.98; P=0.04) in favor of epcor. An OS comparison starting at C3 with longer glofit follow-up demonstrated a consistent survival advantage in favor of epcor (HR 0.68, 95% CI 0.46, 1.01; P=0.05). The proportion of pts who received CAR T or ASCT subsequent therapy were similar for epcor and glofit (CAR T: 7.0% vs 8.9%; ASCT: 6.4% vs 6.3%) (National Institute for Health and Care Excellence Glofit Single Technology Appraisal, 2023). The MAIC analysis showed comparable PFS between epcor and glofit (HR 1.06, 95% CI 0.79, 1.41; P=0.71), although there was substantial censoring in the glofit PFS curve due to immature follow-up. With longer follow-up in the analysis starting at C3, with less censoring, the glofit PFS curve remained similar to the epcor PFS curve from C3 until month 6 (HR 0.67, 95% CI 0.42, 1.07; P=0.10), where separation of the PFS curves were observed favoring epcor (HR 0.56, 95% CI 0.33, 0.97; P=0.04). Median DoCR was longer for epcor (36.1 months) vs glofit (26.9 months). Conclusion: These indirect treatment comparisons suggest that epcor may provide an overall survival benefit over glofit through longer PFS with more mature follow-up, potentially driven by longer DoCR. Survival data with longer follow-up in the full glofit cohort are needed to confirm these findings.

BACKGROUND AND OBJECTIVES: First-line therapy for most intracranial dural arteriovenous fistulas (dAVFs) is endovascular embolization, but some require microsurgical ligation due to limited endovascular accessibility, anticipated lower cure rates, or unacceptable risk profiles. We investigated the most common surgically treated dAVF locations and the approaches and outcomes of each. METHODS: The Consortium for Dural Arteriovenous Fistula Outcomes Research database was retrospectively reviewed. Patients who underwent dAVF microsurgical ligation were included. Patient demographics, angiographic information, surgical details, and postoperative outcomes were collected. The 5 most common surgically treated dAVF locations were analyzed about used surgical approaches and postoperative outcomes. Univariate analyses were performed with statistical significance set at a threshold of P < .05. RESULTS: In total, 248 patients in the Consortium for Dural Arteriovenous Fistula Outcomes Research database met inclusion criteria. The 5 most common surgically treated dAVF locations were tentorial, anterior cranial fossa (ACF), transverse-sigmoid sinus (TSS), convexity/superior sagittal sinus (SSS), and torcular. Most tentorial dAVFs were approached using a suboccipital, lateral supracerebellar infratentorial approach (39.3%); extended retrosigmoid approach (ERS) (25%); or posterior subtemporal approach (19.6%). All ACF dAVFs used a subfrontal approach; 5.3% also included an anterior interhemispheric approach. Most TSS dAVFs were ligated via ERS (31.3%) or subtemporal (31.3%) approaches. All convexity/SSS dAVFs used an interhemispheric approach. All torcular dAVFs used the suboccipital, lateral supracerebellar infratentorial approach, with 10.5% undergoing simultaneous ERS craniotomy. Angiographic occlusion rates after microsurgery were 85.5%, 100%, 75.8%, 79.2%, and 73.7% for tentorial, ACF, TSS, convexity/SSS, and torcular dAVFs, respectively ( P = .02); the permanent neurological complication rates were 1.8%, 2.6%, 9.1%, 0%, and 0% ( P = .31). There were no statistically significant differences in development of complications ( P = .08) or Modified Rankin Scale at the last follow-up ( P = .11) by fistula location. CONCLUSION: Although endovascular embolization is the first-line treatment for most intracranial dAVFs, surgical ligation is an important alternative. ACF and tentorial fistulas particularly demonstrate high rates of postoperative obliteration.

OBJECTIVE The placement of flow-diverting devices has become a common method of treating unruptured intracranial aneurysms of the internal carotid artery. The progressive improvement of aneurysm occlusion after treatment—with low complication and rupture rates—has led to a dilemma regarding the management of aneurysms in which occlusion has not occurred within 6–24 months. The authors aimed to identify clinical consensus regarding management of intracranial aneurysms displaying persistent filling 6–24 months after flow diversion and to ascertain questions that may drive future investigation. METHODS An international panel of 67 experts was invited to participate in a multistep Delphi consensus process on the treatment of intracranial aneurysms after failed flow diversion. RESULTS Of the 67 experts invited, 23 (34%) participated. Qualitative analysis of an initial survey with open-ended questions resulted in 51 statements regarding management of aneurysms showing persistent filling after flow diversion. The statements were grouped into 8 categories, and in the second round, respondents rated the degree of their agreement with each statement on a 5-point Likert scale. Flow diverters with surface modifiers did not influence administration of dual-antiplatelet therapy according to 83%. Consensus was also reached regarding the definition of treatment failure at specific time points, including at 6 months if there is aneurysm growth or persistent rapid flow through the entirety of the aneurysm (96%), at 12 months if there is aneurysm growth or symptom onset (78%), and at 24 months if there is persistent filling regardless of size and filling characteristics (74%). Although experts agreed that the degree of intimal hyperplasia or in-device stenosis could not be ascertained by noninvasive imaging alone (83%), only 65% chose digital subtraction angiography as the preferred modality. At 6 and 12 months, retreatment is preferred if there is persistent filling with aneurysm growth (96%, 96%), device malposition (48%, 87%), or a history of subarachnoid hemorrhage (65%, 70%), respectively, and at 24 months if there is persistent filling without reduction in aneurysm size (74%). Experts favored treatment with an additional flow diverter (87%) over aneurysm clipping, applying the same principles for follow-up (83%) and treatment failure (91%) as for the first flow diverter. CONCLUSIONS The authors present the consensus practices of experts in the management of intracranial aneurysms without occlusion 6–24 months after treatment with a flow-diverting device.

BACKGROUND AND OBJECTIVES: The impact of race on outcomes in the treatment of intracranial aneurysm (IA) remains unclear. We aimed to investigate the relationship between race classified into White, Black, Hispanic, and other and treatment outcomes in patients with ruptured and unruptured IAs. METHODS: The study population consisted of 2836 patients with IA with endovascular treatment or microsurgical treatment (MST) from 16 centers in the United States and Asia, all participating in the observational “STAR” registry. The primary outcome was a 90-day modified Rankin Scale of 0 to 2. Secondary outcomes included periprocedural cerebral infarction and intracranial hemorrhage, perioperative symptomatic cerebral vasospasm in ruptured IA and mortality, and all causes of mortality within 90 days. RESULTS: One thousand fifty-three patients were White (37.1%), 350 were Black (12.3%), 264 were Hispanic (9.3%), and 1169 were other (41.2%). Compared with White patients, Hispanic patients had a significantly lower proportion of primary outcome (adjusted odds ratio [aOR] 0.36, 95% CI, 0.23-0.56) and higher proportion of the periprocedural cerebral infarction, perioperative mortality, and all causes of mortality (aOR 2.53, 95% CI, 1.40-4.58, aOR 1.84, 95% CI, 1.00-3.38, aOR 1.83, 95% CI, 1.06-3.17, respectively). Outcomes were not significantly different in Black and other patients. The subgroup analysis showed that Hispanic patients with age ≥65 years (aOR 0.19, 95% CI, 0.10-0.38, interaction P = .048), Hunt-Hess grades 0 to 3 (aOR 0.29, 95% CI, 0.19-0.46, interaction P = .03), and MST (aOR 0.24, 95% CI, 0.13-0.44, interaction P = .04) had a significantly low proportion of primary outcome. CONCLUSION: This study demonstrates that Hispanic patients with IA are more likely to have a poor outcome at 90 days after endovascular treatment or MST than White patients. Physicians have to pay attention to the selection of treatment modalities, especially for Hispanic patients with specific factors to reduce racial discrepancies.

Introduction Dural arteriovenous fistulas (dAVFs) have been associated with rapidly progressive dementia in relatively young patients. However, the specific angioarchitecture and characteristics of these dAVFs remain to be fully described. To better understand the specific characteristics of dAVFs associated with cognitive impairment (dAVF‐CI), we utilized the CONDOR multicenter database, which provides a large cohort of dAVF available. By analyzing data from patients with dAVFs‐ CI, we aimed to identify the key features distinguishing these cases and elaborate on the pathophysiology of dAVF‐CI. Methods CONDOR is an international multicenter database comprising 1077 (dAVFs) from 14 international centers. We conducted a retrospective analysis of the CONDOR database, focusing on patients diagnosed with dAVFs‐CI. Propensity score matching analysis was performed to compare Borden type II and type III dAVFs with and without cognitive impairment as control groups. Only dAVFs with cortical venous drainage were included as this aggressive subtype can present with non‐hemorrhagic neurologic deficits. Additionally, logistic regression was then employed to identify significant characteristics associated with dAVF‐CI. Results A total of 60 patients with dAVF‐CI and 60 control dAVFs were included in the analysis. The patients with dAVF‐CI had a mean age of 58 ± 18 years. It was found that all cases of dAVF‐CI exhibited venous hypertension. Additionally, there was a significant association between sinus stenosis and dAVF‐CI (OR: 2.85, 95% CI: 1.16‐7.55, p = 0.027). Moreover, dAVF‐CI cases were characterized by the presence of multiple arteriovenous shunts, with more arterial feeders (OR 1.56, 95% CI 1.22‐2.05, p <0.001) and draining veins (OR 2.05, 95% CI 1.05‐4.46, p = 0.004) compared to the control dAVFs. Venous ectasia was also found to be associated with dAVF‐CI (OR 2.38, 95% CI 1.13‐5.11, p= 0.024). Finally, some patients in which successful dAVF closure was achieved had symptom resolution during follow‐up (OR 2.86, 95% CI 0.85‐9.56, p = 0.09). Conclusion dAVFs‐CI tend to occur in relatively young patients and are characterized by the presence of venous hypertension. The development of sinus stenosis and venous ectasia further hinders proper drainage, contributing to the persistence of venous hypertension. Venous hypertension may impair critical structures such as the thalamus or the cortex leading to rapid cognitive impairment. Successful treatment of dAVFs‐CI can potentially reverse symptoms. Nonetheless, some dAVF‐CI may have persistent symptoms due to chronic hypertension and infarction.