A data-driven quality-score system for rating drug products and its implications for the health care industry.

The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products.

Primary and radiation induced skull base osteosarcoma: a systematic review of clinical features and treatment outcomes.

PURPOSE: We aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced skull-base osteosarcoma (SBO). METHODS: PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including SBO cases and sufficient clinical outcome data were included. A comprehensive clinical characteristic review and survival analysis were also conducted. RESULTS: Forty-one studies describing 67 patients were included. The median age was 31 years (male = 59.7%). The middle skull-base was most commonly involved (52.7%), followed by anterior (34.5%) and posterior (12.7%) skull-base. Headache (27%), exophthalmos (18%), and diplopia (10%) were common presenting symptoms. Sixty-eight percent of patients had primary SBO, while 25% had radiation-induced SBO. Surgery was the main treatment modality in 89% of cases. Chemotherapy was administered in 65.7% and radiotherapy in 50%. Median progression-free survival (PFS) was 12 months, and the overall 5-year survival was 22%. The five-year survival rates of radiation-induced SBO and primary SBO were 39% and 16%, respectively (P < 0.05). CONCLUSION: SBO is a malignant disease with poor survival outcomes. Surgical resection is the primary management modality, in conjunction with chemotherapy and radiotherapy. Radiation-induced SBO has a superior survival outcome as compared to its primary counterpart. Complete surgical resection showed a statistically insignificant survival benefit as compared to partial resection.

Thalamic gliomas in adults: a systematic review of clinical characteristics, treatment strategies, and survival outcomes.

PURPOSE: Thalamic gliomas are rare neoplasms that pose significant surgical challenges. The literature is limited to single-institution retrospective case series. We systematically review the literature and describe the clinical characteristics, treatment strategies, and survival outcomes of adult thalamic gliomas. METHODS: Relevant articles were identified on PubMed, Scopus, and Cochrane databases. Papers containing cases of adult thalamic gliomas with clinical outcome data were included. A comprehensive review of clinical characteristics and survival analysis was conducted. RESULTS: We included 25 studies comprising 617 patients. The median age was 45 years (male = 58.6%). Glioblastoma was the most frequent histological type (47.2%), and 82 tumors were H3 K27M-mutant. Motor deficit was the most common presenting symptom (51.8%). Surgical resection was performed in 69.1% of cases while adjuvant chemotherapy and radiotherapy were administered in 56.3% and 72.6%, respectively. Other treatments included laser interstitial thermal therapy, which was performed in 15 patients (2.4%). The lesion laterality (P = 0.754) and the surgical approach (P = 0.111) did not correlate with overall survival. The median progression-free survival was 9 months, and the overall two-year survival rate was 19.7%. The two-year survival rates of low-grade and high-grade thalamic gliomas were 31.0% and 16.5%, respectively. H3 K27M-mutant gliomas showed worse overall survival (P = 0.017). CONCLUSION: Adult thalamic gliomas are associated with poor survival. Complete surgical resection is associated with improved survival rates but is not always feasible. H3 K27M mutation is associated with worse survival and a more aggressive approach should be considered for mutant neoplasms.

Is P&T Ready to Add Rapid Cycle Analytics to Formulary?

Purpose: The intent of this article is to evaluate a novel approach, using rapid cycle analytics and real world evidence, to optimize and improve the medication evaluation process to help the formulary decision making process, while reducing time for clinicians. Summary: The Pharmacy and Therapeutics (P&T) Committee within each health system is responsible for evaluating medication requests for formulary addition. Members of the pharmacy staff prepare the drug monograph or a medication use evaluation (MUE) and allocate precious clinical resources to review patient charts to assess efficacy and value. We explored a novel approach to evaluate the value of our intravenous acetaminophen (IV APAP) formulary admittance. This new methodology, called rapid cycle analytics, can assist hospitals in meeting and/or exceeding the minimum criteria of formulary maintenance as defined by the Joint Commission Standards. In this particular study, we assessed the effectiveness of IV APAP in total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. We assessed the correlation to same-stay opioid utilization, average length of inpatient stay and post anesthesia care unit (PACU) time. Conclusion: We were able to explore and improve our organization's approach in evaluating medications by partnering with an external analytics expert to help organize and normalize our data in a more robust, yet time efficient manner. Additionally, we were able to use a significantly larger external data set as a point of reference. Being able to perform this detailed analytical exercise for thousands of encounters internally and using a data warehouse of over 130 million patients as a point of reference in a short time has improved the depth of our assessment, as well as reducing valuable clinical resources allocated to MUEs to allow for more direct patient care. This clinically real-world and data-rich analytics model is the necessary foundation for using Artificial or Augmented Intelligence (AI) to make real-time formulary and drug selection decisions.

Academic neurosurgery in the UK: present and future directions.

Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK's international standing is considered.

Ectopic Cushing's syndrome secondary to olfactory neuroblastoma.

We present the case of a patient with Cushing's syndrome secondary to ectopic ACTH secretion. A MR of the head showed a left-sided nasal mass extending down from the cribriform plate. The patient underwent endoscopic resection with nearly complete removal of the mass. Histological examination showed an ACTH-secreting olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal range after surgery and have remained normal for over a year. ONB is a rare cause for ectopic ACTH secretion. This case highlights the diagnostic and management difficulties in patients with ectopic ACTH secretion, and provides a brief review of ONB.

Real-time ultrasound-guided external ventricular drain placement: technical note.

In the United Kingdom, ultrasound-guided external ventricular drain (EVD) insertion is becoming the standard of care to mitigate the morbidity associated with catheter malposition and multiple passes. Many neurosurgeons routinely use ultrasound to check the preinsertion trajectory, although real-time visualization of ventricular cannulation is preferable since minor deviations can be significant in patients with smaller ventricles, and live visualization further enables the catheter tip to be adjusted away from the choroid plexus. Such real-time ultrasound navigation has traditionally been limited by technical factors including the challenge of simultaneously manipulating the probe and inserting the catheter within the same image plane. The authors here describe a simple technique for precise EVD placement using a readily available bur hole ultrasound transducer attached to a 10-gauge needle guide channel (principally used for biopsy procedures) to accommodate a ventriculostomy catheter. The anticipated trajectory line is then projected onto the display and followed into the ipsilateral lateral ventricle. This is illustrated with a representative case and video demonstrating this rapid, user-friendly, and reliable technique. The authors invite others to consider this useful technique to minimize the risks of catheter misplacement or multiple cannulation attempts, which can be of particular benefit to junior neurosurgeons performing difficult cases under pressured conditions.

Development of a pharmacy technician training program and advanced pharmacy technician roles: A health system's journey amidst an evolving national practice landscape.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

The assessment of gender differences in perceptual fear generalization and related processes.

In this study we aimed to investigate gender differences in fear generalization tendencies in humans and, inspired by recent findings in animal research, examine whether any such differences could stem from differences in memory precision. Forty men and forty women underwent a differential fear conditioning procedure using geometric shapes as cues. Subsequently, generalized fear responses were assessed across a spectrum of perceptually similar shapes. Throughout generalization testing, perceptual memory accuracy was repeatedly probed using a stimulus recreation task. Using statistical and computational modeling, we found strong evidence for the absence of gender differences in fear learning and generalization behavior. The evidence for gender differences in related processes such as perception and memory was inconclusive. Although some of our findings hinted at the possibility that women may be more perceptive of physical differences between stimuli and have more accurate memory than men, those observations were not consistently replicated across experimental conditions and analytical approaches. Our results contribute to the emerging literature on gender differences in perceptual fear generalization in humans and underscore the need for further systematic research to explore the interplay between gender and mechanisms associated with fear generalization across different experimental contexts.

Treatment and outcomes of IDH1-mutant gliomas in elderly patients.

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutations in both high- and low-grade gliomas are associated with an increase in survival compared with IDH-wild-type (IDHwt) tumors. A rare and understudied population is elderly individuals, ≥ 65 years of age, who have IDH1-R132H-mutant (IDHmt) gliomas. The objective of this paper was to characterize the institutions' experience with IDHmt gliomas in a patient population ≥ 65 years of age over the last 10 years. METHODS: A retrospective study of individuals ≥ 65 years of age with IDHmt gliomas treated between 2010 and 2020 at Memorial Sloan Kettering was performed. RESULTS: Twenty-five patients ≥ 65 years of age underwent resection or biopsy with a diagnosis of IDHmt glioma (52% WHO grade II, 32% WHO grade III, and 16% WHO grade IV). The most common presenting symptoms were seizure (28%) and motor or sensory deficits (24%). On preoperative MRI, 56% of tumors demonstrated contrast enhancement and 44% had no enhancement. Most patients underwent craniotomy for resection (n = 23, 92%), with subtotal resection achieved in the majority (16/23, 69.6%). Postoperative discharge location included home (64%), acute rehabilitation (16%), subacute rehabilitation (8%), and unknown (12%). Most patients received postoperative chemotherapy (72%) and radiation therapy (68%). The 2- and 5-year survival rates for the overall cohort were 83.1% (95% CI 69.3%-99.7%) and 69.7% (95% CI 53.2%-91.3%), respectively, with gross-total resection or near-total resection, contrast enhancement, and WHO grade significantly associated with survival. From the clinical sequencing data, no significant differences were identified between younger and older IDHmt cohorts. CONCLUSIONS: While IDH mutation in elderly patients may be rare, these patients have favorable survival relative to their IDHwt counterparts. Age at diagnosis should not be used in isolation to suggest a molecular IDHwt status or poor prognosis when guiding patient treatment decisions.

Transcript-specific enrichment enables profiling rare cell states via scRNA-seq.

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing (scRNA-seq) identifies many rare populations of interest that express specific marker transcript combinations, traditional flow sorting limits our ability to enrich these populations for further profiling, including requiring cell surface markers with high-fidelity antibodies. Additionally, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers. To address these limitations, we describe Programmable Enrichment via RNA Flow-FISH by sequencing (PERFF-seq), a scalable assay that enables scRNA-seq profiling of subpopulations from complex cellular mixtures defined by the presence or absence of specific RNA transcripts. Across immune populations (n = 141,227 cells) and fresh-frozen and formalin-fixed paraffin-embedded brain tissue (n = 29,522 nuclei), we demonstrate the sorting logic that can be used to enrich for cell populations via RNA-based cytometry followed by high-throughput scRNA-seq. Our approach provides a rational, programmable method for studying rare populations identified by one or more marker transcripts.

Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

OBJECTIVE: Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS). METHODS: Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk. RESULTS: This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01). CONCLUSIONS: The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

The idiosyncratic nature of how individuals perceive, represent, and remember their surroundings and its impact on learning-based generalization.

The current study adopted a multimodal assessment approach to map the idiosyncratic nature of how individuals perceive, represent, and remember their surroundings and to investigate its impact on learning-based generalization. During an online differential conditioning paradigm, participants (n = 105) learned the pairing between a blue color patch (CS +) and an outcome (i.e., shock symbol) and the unpairing between a green color patch and the same outcome. After the learning task, the generalization of outcome expectancies was assessed to 14 stimuli spanning the entire blue-green color spectrum. Hereafter, a stimulus identification task assessed the ability to correctly identify the CS + among this stimulus range. Continuous and binary color category membership judgments of the stimuli were assessed preconditioning. We found that a response model with color perception and identification performance as sole predictors was preferred to contemporary approaches that use stimulus as a predictor. Interestingly, incorporating interindividual differences in color perception, CS identification, and color categories significantly improved the models' ability to account for different generalization patterns. Our findings suggest that insight into the idiosyncratic nature of how individuals perceive, represent, and remember their surroundings provides exciting opportunities to understand post-learning behaviors better. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Individual differences in stimulus identification, rule induction, and generalization of learning.

In the field of stimulus generalization, an old yet unresolved discussion pertains to what extent stimulus misidentifications contribute to the pattern of conditioned responding. In this article, we perform cluster analysis on six datasets (four published datasets and two unpublished datasets, included N = 950) to examine the relationship between interindividual differences in (a) stimulus identification, (b) patterns of generalized responding, and (c) verbalized generalization rules. The datasets were obtained from online predictive learning tasks where participants learned associations between colored cues and the presence or absence of a hypothetical outcome. In these datasets, stimulus identification and expectancy ratings were assessed in separate phases to a range of colors varying between blue-green. Using cluster analyses on performance during stimulus identification, we identified different subgroups of participants (good vs. bad identifiers). In all six datasets, we found a close relationship between the pattern of stimulus identification and the shape of the expectancy gradient across the test dimension between the identified subgroups. Furthermore, participants classified as good identifiers were more likely to report a similarity generalization rule than a relational or linear rule, suggesting that individual differences in stimulus identification are related to individual differences in generalization rules. These findings suggest that greater consideration should be given to interindividual variability in stimulus identification, inductive rules, and their relationship in explaining patterns of generalized responses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Humans display interindividual differences in the latent mechanisms underlying fear generalization behaviour.

Human generalization research aims to understand the processes underlying the transfer of prior experiences to new contexts. Generalization research predominantly relies on descriptive statistics, assumes a single generalization mechanism, interprets generalization from mono-source data, and disregards individual differences. Unfortunately, such an approach fails to disentangle various mechanisms underlying generalization behaviour and can readily result in biased conclusions regarding generalization tendencies. Therefore, we combined a computational model with multi-source data to mechanistically investigate human generalization behaviour. By simultaneously modelling learning, perceptual and generalization data at the individual level, we revealed meaningful variations in how different mechanisms contribute to generalization behaviour. The current research suggests the need for revising the theoretical and analytic foundations in the field to shift the attention away from forecasting group-level generalization behaviour and toward understanding how such phenomena emerge at the individual level. This raises the question for future research whether a mechanism-specific differential diagnosis may be beneficial for generalization-related psychiatric disorders.

Examining the impact of cue similarity and fear learning on perceptual tuning.

Past research on the effects of associative aversive learning on discrimination acuity has shown mixed results, including increases, decreases, and no changes in discrimination ability. An animal study found that the type of learning experience determined the direction and extent of learning-induced changes. The current preregistered web-based study aimed to translate these findings to humans. Experiment 1 (N = 245) compared changes in stimulus discrimination between simple learning (only one oriented grating cue), coarse differential conditioning (physically distinct cues), and fine differential conditioning (physically similar cues) as well as to their three respective control groups. The discrimination task consisted of a two-alternative-forced-choice task with oriented grating stimuli. During learning, a specific orientation was paired with unpleasant pictures. Our analysis using generative modeling demonstrated weak to moderate evidence that aversive learning did not alter discrimination acuity in any of the groups. In a follow-up experiment (N = 121), we replicated these findings despite successful learning trajectories in all three groups and a more detailed assessment of discrimination acuity. Contrary to prior assumptions, our findings indicate that aversive learning does not enhance perceptual discrimination, and the presence of additional safety cues does not appear to moderate this effect.

Orbital Exenteration for Craniofacial Lesions: A Systematic Review and Meta-Analysis of Patient Characteristics and Survival Outcomes.

BACKGROUND: The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the clinical outcomes of OE, including surgical outcomes and overall survival (OS). METHODS: Relevant articles were retrieved from Medline, Scopus, and Cochrane according to PRISMA guidelines. A systematic review and meta-analysis were conducted on the clinical characteristics, management, and outcomes. RESULTS: A total of 33 articles containing 957 patients who underwent OE for CFLs were included (weighted mean age: 64.3 years [95% CI: 59.9-68.7]; 58.3% were male). The most common lesion was squamous cell carcinoma (31.8%), and the most common symptom was disturbed vision/reduced visual acuity (22.5%). Of the patients, 302 (31.6%) had total OE, 248 (26.0%) had extended OE, and 87 (9.0%) had subtotal OE. Free flaps (33.3%), endosseous implants (22.8%), and split-thickness skin grafts (17.2%) were the most used reconstructive methods. Sino-orbital or sino-nasal fistula (22.6%), flap or graft failure (16.9%), and hyperostosis (13%) were the most reported complications. Regarding tumor recurrences, 38.6% were local, 32.3% were distant, and 6.7% were regional. The perineural invasion rate was 17.4%, while the lymphovascular invasion rate was 5.0%. Over a weighted mean follow-up period of 23.6 months (95% CI: 13.8-33.4), a weighted overall mortality rate of 39% (95% CI: 28-50%) was observed. The 5-year OS rate was 50% (median: 61 months [95% CI: 46-83]). The OS multivariable analysis did not show any significant findings. CONCLUSIONS: Although OE is a disfiguring procedure with devastating outcomes, it is a viable option for carefully selected patients with advanced CFLs. A patient-tailored approach based on tumor pathology, extension, and overall patient condition is warranted.

Middle meningeal artery embolization using cone-beam computed tomography augmented guidance in patients with cancer.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of middle meningeal artery embolization (MMAE) performed under cone-beam computed tomography (CBCT) augmented guidance in patients with cancer. MATERIALS AND METHODS: Eleven patients with cancer (seven women, four men; median age, 75 years; age range: 42-87 years) who underwent 17 MMAEs under CBCT with a combination of particles and coils for chronic subdural hematoma (SDH) (n = 6), postoperative SDH (n = 3), or preoperative embolization of meningeal tumor (n = 2) from 2022 to 2023 were included. Technical success, fluoroscopy time (FT), reference dose (RD), kerma area product (KAP) were analyzed. Adverse events and outcomes were recorded. RESULTS: The technical success rate was 100% (17/17). Median MMAE procedure duration was 82 min (interquartile range [IQR]: 70, 95; range: 63-108 min). The median FT was 24 min (IQR: 15, 48; range: 21.5-37.5 min); the median RD was 364 mGy (IQR: 37, 684; range: 131.5-444.5 mGy); and the median KAP was 46.4 Gy.cm2 (9.6, 104.5; range: 30.2-56.6 Gy.cm2). No further interventions were needed. The adverse event rate was 9% (1/11), with one pseudoaneurysm at the puncture site in a patient with thrombocytopenia, which was treated by stenting. The median follow-up was 48 days (IQR; 14, 251; range: 18.5-91 days]. SDH reduced in 11 of 15 SDHs (73%) as evidenced by follow-up imaging, with a size reduction greater than 50% in 10/15 SDHs (67%) . CONCLUSION: MMAE under CBCT is a highly effective treatment option, but appropriate patient selection and careful consideration of potential risks and benefits is important for optimal patient outcomes.

Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis.

Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we show CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples. Meaningful clinico-genomic correlations are noted, namely EGFR alterations in leptomeningeal disease (LMD) and MYC amplifications in multifocal regional brain progression. Patients who developed early LMD frequently have had uncommon, multiple, and persistently detectable EGFR driver mutations. The distinct mutational patterns identified in BM specimens compared to other tissue sites suggest specific biologic underpinnings of intracranial progression.

Characterization of Central Nervous System Clinico-Genomic Outcomes in ALK-Positive Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Alectinib.

INTRODUCTION: Highly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT. METHODS: We retrospectively reviewed ALK fusion-positive NSCLC patients with BMs who received alectinib at the diagnosis of BM from 1/2012 and 5/2021. Outcome variables included intracranial progression-free survival (iPFS), overall survival (OS), duration of TKI therapy, and CNS response rates. Genomic characteristics from tumor specimens were assessed with MSK-IMPACT, a next-generation sequencing (NGS)-based genomic profiling assay. RESULTS: A total of 38 patients with 114 CNS lesions were included. Twelve of these patients also received contemporaneous LT (SRS, WBRT, or surgical resection). Maximal BM diameter in the TKI + LT group was greater (p < 0.003) but despite this difference, iPFS (TKI only, HR 1.21, 95 % CI 0.51-2.89; p = 0.66) and OS (TKI only, HR 5.99, 95 % CI 0.77-46.6; p = 0.052) were similar between groups and trended towards more favorable outcomes with the addition of LT. SMARCA4 co-alterations were associated with inferior OS (HR 8.76, 1.74-44.2; p = 0.009). CONCLUSIONS: Our study demonstrated that patients with ALK fusion-positive NSCLC treated with TKI + LT had larger BM and higher likelihood of pre-treatment neurologic symptoms. Despite these differences, iPFS was similar between groups. Results should be interpreted with caution as our study was limited by an underpowered sample size. SMARCA4 co-alterations were associated with inferior OS and these findings warrant further investigation.