Citations

BACKGROUND AND OBJECTIVES: Aneurysm risk prediction remains an imprecise science that places patients at risk for either over or undertreatment. Machine learning (ML) models may improve clinical practice by adding precision to risk assessment. This study aims to comprehensively assess the current landscape of ML applications in predicting the risk of aneurysm rupture and compare the performance with the widely used PHASES score. METHODS: A systematic review of PubMed, Scopus, and Web of Science was conducted. All studies using ML tools to predict the rupture risk of intracranial aneurysms were included. Meta-analysis was conducted with consideration to the ML algorithms and compared with the PHASES score. RESULTS: Thirty-six studies involving 22 462 patients were included in the final analysis. ML techniques, including 124 models using 25 algorithms, were employed. Among various ML models, while they had comparable diagnostic performance, deep learning exhibited a slightly better performance profile (sensitivity = 0.792, specificity = 0.788, and accuracy = 0.778 in external validation). Based on our analysis, ML, regardless of the algorithm, provides comparable sensitivity (0.743 vs 0.771, P = .60) and higher specificity (0.763 vs 0.507, P < .01) compared with the PHASES score. Consistently, pooling the area under the receiver operating characteristic curve (AUC) for 60 ML models and 5 PHASES score data, ML models exhibited higher AUC (0.84 vs 0.64, P < .01). Using hemodynamic parameters as input for models improved specificity ( P < .01) in the test sets without any significant changes in the sensitivity. The later improvement was not observed in the external validation sets. CONCLUSION: ML techniques have the potential to enhance the prediction of intracranial aneurysm rupture compared with traditional approaches, like the PHASES score. Incorporating hemodynamic parameters may further enhance the accuracy of ML models. Feature prospective studies are required to validate the utility of ML models for clinical integration.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Abstract Background: Savo is an oral, potent and highly selective MET-TKI. In the Phase 2 SAVANNAH study (NCT03778229), savo + osi had a high rate of durable responses in pts with EGFRm advanced NSCLC and high MET OverExp and/or Amp levels. Early clearance of plasma EGFRm may predict outcomes. We report an exploratory analysis of plasma EGFRm clearance and its association with MET tissue biomarker status, ORR and PFS. Methods: Pts with EGFRm advanced NSCLC and MET OverExp and/or Amp with PD on 1L+ osi received savo 300 mg QD, 300 mg BID or 600 mg QD + osi 80 mg QD. MET OverExp/Amp was centrally confirmed (by IHC [Roche], 3+ intensity in ≥50% of tumor cells [MET IHC3+/≥50%]; by FISH [Abbott Molecular], MET gene copy number ≥5 or MET:CEP7 ratio ≥2 [FISH5+], or at higher thresholds of MET IHC3+/≥90% or FISH10+). Baseline (BL) and Wk 3 plasma EGFRm (Ex19del/L858R) were analyzed by ddPCR (Biodesix) as an estimate of tumor burden. MET Amp was not monitored in ctDNA due to low detection sensitivity. Clearance was defined as undetected EGFRm ctDNA at Wk 3, when detected at BL. PFS was investigator-assessed (RECIST 1.1). DCO: Aug 23, 2024. Results: Of 344 pts with evaluable BL ctDNA, 259 (75%) had detected EGFRm ctDNA. Of these, 225 had evaluable ctDNA at Wk 3 (82 [36%] had EGFRm clearance at Wk 3). Confirmed ORR was higher in pts with EGFRm Wk 3 clearance (56/82; 68%) vs non-clearance (38/143; 27%). PFS was longer in pts with vs without EGFRm clearance at Wk 3 (Table). Across all pts evaluable for ctDNA at Wk 3, clearance rates were higher in pts with vs without high MET (69/162 [43%] vs 13/63 [21%]; odds ratio [95% CI] 0.35 [0.16, 0.72]). Similar results were seen in the savo 300 mg QD + osi subgroup. Conclusions: In SAVANNAH, among pts with detected EGFRm ctDNA at BL, clearance at Wk 3 was associated with improved ORR and PFS. Plasma EGFRm clearance at Wk 3 is enriched in pts with MET IHC3+/≥90% or FISH10+ status, consistent with improved efficacy in this biomarker subgroup. Citation Format: Jonathan W. Riess, Filippo de Marinis, Benjamin Levy, Tae Min Kim, Laura Bonanno, Quincy Chu, Marcello Tiseo, Adrian Sacher, Silvia Novello, Christina Baik, Lyudmila Bazhenova, Jacques Cadranel, Giulio Metro, Cheng-Ta Yang, Tsung-Ying Yang, Gee-Chen Chang, Konstantinos Leventakos, Lorenzo Livi, James Chih-Hsin Yang, Lecia V. Sequist, John Argue, Wanning Xu, Aleksandra Markovets, Ryan Hartmaier, Myung-Ju Ahn. SAVANNAH: Clearance of plasma EGFRm in patients with EGFRm MET-overexpressed (OverExp) and/or -amplified (Amp) NSCLC post-osimertinib (osi) treated with savolitinib (savo) + osi [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB416.

Abstract Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as “lineage drift” were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of &lt;40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.

OBJECTIVE Core outcome sets (COSs) are needed to promote data consistency across studies as well as data synthesis and comparability. The goal of the current study was to utilize a modified Delphi process to develop a COS–sciatic injury and neuropathy evaluation (COS-SINE). METHODS A five-stage approach was utilized to develop the COS-SINE: stage 1, consortium development; stage 2, literature review to identify potential outcome measures; stage 3, Delphi survey to develop consensus on outcomes for inclusion; stage 4, Delphi survey to develop definitions; and stage 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set–STAndards for Development recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. Three participants were excluded on the basis of agreed upon participation rules. The final COS-SINE consisted of 36 data points/outcomes covering the domains of demographics, diagnostics, patient-reported outcomes, motor and sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 24 months, with consensus optimal time points for assessment identified as preoperatively and 3, 6, 12, 24, and 36 months postoperatively. CONCLUSIONS The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-SINE should serve as a minimum set of data that should be collected in all future neurosurgical studies on sciatic nerve injury and neuropathy. Incorporation of this COS should help improve consistency in reporting and data synthesis and comparability and should minimize outcome-reporting bias.

Abstract “Nonclassical” myeloproliferative neoplasms (MPNs) and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) represent a heterogeneous group of malignancies characterized by a wide range of clinical manifestations. Unlike classical MPNs, there is no standardized management approach for these conditions, particularly concerning the indications for and management of allogeneic hematopoietic cell transplantation. To address this gap, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines (PH&G) Committee and the Chronic Malignancies Working Party (CMWP) have collaborated to develop shared guidelines aimed at optimizing the selection and management of patients with these rare forms of neoplasms. A comprehensive review of the literature from the publication of the revised fourth edition of the (2016) World Health Organization classification onward was conducted. A multidisciplinary group of experts in the field convened to produce this document, which was developed through multiple rounds of draft circulation. Key recommendations include the early identification of potential transplant candidates, particularly in cases of chronic neutrophilic leukemia, chronic eosinophilic leukemia (CEL)/CEL, not otherwise specified (CEL-NOS), myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions with FGFR1, JAK2, ABL1, and FLT3 rearrangements, MDS/MPN with neutrophilia/atypical chronic myeloid leukemia, and MDS/MPN, NOS. For patients with MPN, NOS/MPN unclassifiable, standard recommendations for myelofibrosis should be applied. Similarly, in MDS/MPN with thrombocytosis, transplantation is recommended on the basis of established MDS guidelines. Given the current lack of robust evidence, this document will serve as a valuable resource to guide future research activities, providing a framework for addressing critical unanswered questions and advancing the field.

Abstract Introduction The impact of multiple feeding arteries on clinical outcomes of cerebral arteriovenous malformations (AVMs) is not well understood. This study aims to compare outcomes between AVMs with multiple versus single feeding arteries. Patients and Methods Data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium were analyzed. Propensity score matching (PSM) was used to balance cohorts. Subgroup analysis was conducted for ruptured and unruptured AVMs and different treatment options, and multivariable logistic regression was applied to assess the impact of feeding artery origin. Results Among 953 patients, 661(69.4%) had multiple feeding arteries, and 292 (30.6%) had a single feeding artery. After PSM, which included 422 matched patients (211 in each group), the differences in obliteration rates (68.7% vs 74.8%, OR 0.73, 95% CI: 0.48–1.12, p = 0.16) and symptomatic complications (15.6% vs 11.8%, OR 1.37, 95% CI: 0.78–2.41, p = 0.25) were not significant. Subgroup analysis comparing ruptured and unruptured AVMs and different treatment options showed no significant differences across all subgroups. Multivariable analysis identified PICA feeders as significantly associated with increased odds of all complications (OR 7.33, 95% CI: 2.14–25.1, p = 0.002). Discussion and Conclusion AVMs with a single feeding artery were more likely to present with rupture, but no significant differences in obliteration rates or complications were observed between the groups after PSM. These findings suggest that while the number of feeding arteries may influence the initial presentation, it does not appear to impact overall treatment success or patient prognosis. Further prospective studies are needed to confirm these findings.

ABSTRACTObjectivesThis final post hoc analysis evaluated patient‐reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D‐Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5‐month follow‐up in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.MethodsKey scales from the EORTC QLQ‐C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.ResultsThe intent‐to‐treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D‐Rd‐treated patients showed improvements from baseline that were sustained over 5 years in the intent‐to‐treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D‐Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16–2.91]), physical functioning (1.93 [1.18–3.14]), pain (1.41 [0.90–2.22]), and fatigue (2.00 [1.24–3.23]). Greater proportions of patients with bone lesions improved with D‐Rd versus Rd on GHS and physical functioning.ConclusionsIn transplant‐ineligible patients with NDMM, D‐Rd improved health‐related quality of life over a 5‐year period versus Rd. Trial Registration: ClinicalTrials.gov: NCT02252172