David H Viskochil, Mariusz Wysocki, Maria Learoyd, Peng Sun, Karen So, Azura Evans, Francis Lai, Héctor Salvador Hernàndez
{"title":"Effect of food on selumetinib pharmacokinetics and gastrointestinal tolerability in adolescents with neurofibromatosis type 1-related plexiform neurofibromas","authors":"David H Viskochil, Mariusz Wysocki, Maria Learoyd, Peng Sun, Karen So, Azura Evans, Francis Lai, Héctor Salvador Hernàndez","doi":"10.1093/noajnl/vdae036","DOIUrl":"https://doi.org/10.1093/noajnl/vdae036","url":null,"abstract":"\u0000 \u0000 \u0000 Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN.\u0000 \u0000 \u0000 \u0000 Eligible participants aged ≥12–<18 years took 25 mg/m2 selumetinib BID with a low-fat meal (T1) for 28 days, followed by a 7-day washout, and then administration in a fasted state (T2) for another 28 days. Primary objectives were to evaluate the effect of a low-fat meal on AUC0−12,ss and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters, and adverse events (AEs).\u0000 \u0000 \u0000 \u0000 At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC0−12,ss between T1 and T2. In T1 and T2, 29.2% and 33.3% participants, respectively, reported ≥1 GI AE. No GI AEs Grade ≥3, or serious AEs, or GI AEs resulting in treatment interruptions, discontinuation, or dose reductions were reported in T1 and T2.\u0000 \u0000 \u0000 \u0000 Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC0−12,ss nor GI tolerability in adolescents with NF1-PN.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"122 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140235998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongjuan Chen, Aaminah Khan, Christopher Katsinas, Filip Michniewich, Jessie Goldberg, Laura Franshaw, M. Tsoli, D. S. Ziegler
{"title":"Preclinical evaluation of protein synthesis inhibitor omacetaxine in pediatric brainstem gliomas","authors":"Yongjuan Chen, Aaminah Khan, Christopher Katsinas, Filip Michniewich, Jessie Goldberg, Laura Franshaw, M. Tsoli, D. S. Ziegler","doi":"10.1093/noajnl/vdae029","DOIUrl":"https://doi.org/10.1093/noajnl/vdae029","url":null,"abstract":"\u0000 \u0000 \u0000 Diffuse Intrinsic Pontine Gliomas (DIPGs) pose a significant challenge as a highly aggressive and currently incurable form of pediatric brain cancer, necessitating the development of novel therapeutic strategies. Omacetaxine, an FDA-approved protein synthesis inhibitor for treating certain hematological malignancies, was investigated for its potential antitumor effects against preclinical DIPG models.\u0000 \u0000 \u0000 \u0000 We employed primary DIPG cultures to study omacetaxine's cytotoxicity and its impact on colony formation. Annexin V staining and flow cytometry assessed apoptosis. Wound healing assays evaluated migration, while western blotting determined inhibition of oncogenic proteins. We tested omacetaxine's therapeutic efficacy in an orthotopic DIPG model and assessed brain penetration using mass spectrometry.\u0000 \u0000 \u0000 \u0000 We found a pronounced cytotoxic activity of omacetaxine against DIPG neurospheres, with low IC50 values of approximately 20 nM. Omacetaxine exerted its anti-proliferative effect by inhibiting protein synthesis and the induction of apoptotic pathways, evidenced by significant elevated levels of cleaved caspase 3 and cleaved PARP, both key markers of apoptosis. Omacetaxine effectively targeted oncogenic players such as PDGFRα and PI3K without additional effects on the mTOR signaling pathway. Furthermore, our study revealed the inhibitory effects of omacetaxine on cell migration, and a significant reduction in integrin/FAK signaling, which plays a crucial role in tumor progression and metastasis.\u0000 \u0000 \u0000 \u0000 Despite these promising in vitro effects, omacetaxine’s efficacy in an orthotopic DIPG model was limited due to inadequate penetration across the blood-brain barrier. As such, further research and advancements are crucial to improve the drug's brain penetration, thus enhancing its overall therapeutic potential.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"81 s1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140236279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ugur T Sener, Mahnoor Islam, M. Webb, S. Kizilbash
{"title":"Antiangiogenic exclusion rules in glioma trials: Historical perspectives and guidance for future trial design","authors":"Ugur T Sener, Mahnoor Islam, M. Webb, S. Kizilbash","doi":"10.1093/noajnl/vdae039","DOIUrl":"https://doi.org/10.1093/noajnl/vdae039","url":null,"abstract":"\u0000 \u0000 \u0000 Despite lack of proven therapies for recurrent high-grade glioma (HGG), only 8-11% of patients with glioblastoma participate in clinical trials, partly due to stringent eligibility criteria. Prior bevacizumab treatment is a frequent exclusion criterion, due to difficulty with response assessment and concerns for rebound edema following antiangiogenic discontinuation. There are no standardized trial eligibility rules related to prior antiangiogenic use.\u0000 \u0000 \u0000 \u0000 We reviewed ClinicalTrials.gov listings for glioma studies starting between May 2009 and July 2022 for eligibility rules related to antiangiogenics. We also reviewed the literature pertaining to bevacizumab withdrawal.\u0000 \u0000 \u0000 \u0000 Two-hundred-ninety-seven studies for patients with recurrent glioma were reviewed. Most were phase 1 (n=145, 49%), non-randomized (n=257, 87%), evaluated a drug-only intervention (n=223, 75%), and had a safety and tolerability primary objective (n=181, 61%). Fifty-one (17%) excluded participants who received any antiangiogenic, one (0.3%) excluded participants who received any non-temozolomide systemic therapy. Fifty-nine (20%) outlined washout rules for bevacizumab (range 2-24 weeks, 4-week washout n=35, 12% most common). Seventy-eight required a systemic therapy washout (range 1-6 weeks, 4-week washout n=34, 11% most common). Nine permitted prior bevacizumab use with limitations, 18 (6%) permitted any prior bevacizumab, 5 (2%) were for bevacizumab-refractory disease, 76 (26%) had no rules regarding antiangiogenic use. A literature review is then presented to define standardized eligibility criteria with a six-week washout period proposed for future trial design.\u0000 \u0000 \u0000 \u0000 Interventional clinical trials for patients with HGG have substantial heterogeneity regarding eligibility criteria pertaining to bevacizumab use, demonstrating a need for standardizing clinical trial design.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"13 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140240899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Lulla, A. Buxton, Mark D Krailo, Margot A. Lazow, D. Boue, James L Leach, T. Lin, James I Geller, S. Kumar, Marina N Nikiforova, Uma Chandran, Sachin S Jogal, Marvin D Nelson, A. Onar-Thomas, D. Haas-Kogan, Kenneth J Cohen, M. Kieran, A. Gajjar, R. Drissi, Ian F Pollack, M. Fouladi
{"title":"Vorinostat, temozolomide (TMZ) or bevacizumab (BEV) with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children’s Oncology Group Study","authors":"R. Lulla, A. Buxton, Mark D Krailo, Margot A. Lazow, D. Boue, James L Leach, T. Lin, James I Geller, S. Kumar, Marina N Nikiforova, Uma Chandran, Sachin S Jogal, Marvin D Nelson, A. Onar-Thomas, D. Haas-Kogan, Kenneth J Cohen, M. Kieran, A. Gajjar, R. Drissi, Ian F Pollack, M. Fouladi","doi":"10.1093/noajnl/vdae035","DOIUrl":"https://doi.org/10.1093/noajnl/vdae035","url":null,"abstract":"\u0000 \u0000 \u0000 Outcomes for children with high-grade gliomas (HGG) remain poor. This multicenter phase II trial evaluated whether concurrent use of vorinostat or bevacizumab with focal radiotherapy (RT) improved 1-year event-free survival (EFS) compared to temozolomide in children with newly-diagnosed HGG who received maintenance temozolomide and bevacizumab.\u0000 \u0000 \u0000 \u0000 Patients ≥3 and <22 years with localized, non-brainstem HGG were randomized to receive RT (dose 54-59.4Gy) with vorinostat, temozolomide, or bevacizumab followed by 12 cycles of bevacizumab and temozolomide maintenance therapy.\u0000 \u0000 \u0000 \u0000 Among 90 patients randomized, the 1-year EFS for concurrent bevacizumab, vorinostat, or temozolomide with RT was 43.8% (±8.8%), 41.4% (±9.2%) and 59.3% (±9.5%), respectively with no significant difference among treatment arms. Three- and 5-year EFS for the entire cohort was 14.8% and 13.4%, respectively with no significant EFS difference among the chemoradiotherapy arms. IDH mutations were associated with more favorable EFS (p=0.03), whereas H3.3 K27M mutations (p=0.0045) and alterations in PIK3CA or PTEN (p=0.025) were associated with worse outcomes. Patients with telomerase- and ALT-negative tumors (n=4) had an EFS of 100%, significantly greater than those with ALT or telomerase, or both (p=0.002). While there was no difference in outcomes based on TERT expression, high TERC expression was associated with inferior survival independent of telomere maintenance mechanism (p=0.0012).\u0000 \u0000 \u0000 \u0000 Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly-diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"37 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140242016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Breen, Connie S Geno, M. Waddle, Jing Qian, W. S. Harmsen, Terence C Burns, U. Sener, M. Ruff, B. J. Neth, J. Uhm, D. Routman, Elizabeth S Yan, Jon J. Kruse, Nadia N. Laack, P. D. Brown, Anita Mahajan
{"title":"Proton versus photon craniospinal irradiation for adult medulloblastoma: a dosimetric, toxicity, and exploratory cost analysis","authors":"W. Breen, Connie S Geno, M. Waddle, Jing Qian, W. S. Harmsen, Terence C Burns, U. Sener, M. Ruff, B. J. Neth, J. Uhm, D. Routman, Elizabeth S Yan, Jon J. Kruse, Nadia N. Laack, P. D. Brown, Anita Mahajan","doi":"10.1093/noajnl/vdae034","DOIUrl":"https://doi.org/10.1093/noajnl/vdae034","url":null,"abstract":"\u0000 \u0000 \u0000 This study aimed to determine whether proton craniospinal irradiation (CSI) decreased dose to normal tissue and resulted in less toxicity than photon CSI for adult patients.\u0000 \u0000 \u0000 \u0000 This single institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients.\u0000 \u0000 \u0000 \u0000 Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18-66). Molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all p< 0.001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% vs. 35%, p= 0.044) and decreased median weight loss during radiation (+1.0 vs. -2.8 kg, p= 0.011). Weight loss was associated with acute hospitalization (p= 0.009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At last follow-up, five photon patients had died (two of progressive disease, three without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free.\u0000 \u0000 \u0000 \u0000 This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"30 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140257575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher P Millward, Sumirat M. Keshwara, Terri S Armstrong, H. Barrington, Sabrina Bell, A. Brodbelt, H. Bulbeck, L. Dirven, Paul L Grundy, A. Islim, Mohsen Javadpour, Shelli D Koszdin, Anthony G Marson, Michael W McDermott, Torstein R Meling, Kathy Oliver, P. Plaha, M. Preusser, Thomas Santarius, N. Srikandarajah, M. Taphoorn, Carole Turner, C. Watts, M. Weller, Paula R Williamson, Gelareh Zadeh, A. Z. Zamanipoor Najafabadi, M. Jenkinson
{"title":"The outcomes measured and reported in intracranial meningioma clinical trials: a systematic review","authors":"Christopher P Millward, Sumirat M. Keshwara, Terri S Armstrong, H. Barrington, Sabrina Bell, A. Brodbelt, H. Bulbeck, L. Dirven, Paul L Grundy, A. Islim, Mohsen Javadpour, Shelli D Koszdin, Anthony G Marson, Michael W McDermott, Torstein R Meling, Kathy Oliver, P. Plaha, M. Preusser, Thomas Santarius, N. Srikandarajah, M. Taphoorn, Carole Turner, C. Watts, M. Weller, Paula R Williamson, Gelareh Zadeh, A. Z. Zamanipoor Najafabadi, M. Jenkinson","doi":"10.1093/noajnl/vdae030","DOIUrl":"https://doi.org/10.1093/noajnl/vdae030","url":null,"abstract":"\u0000 \u0000 \u0000 Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarise the outcomes measured and reported in meningioma clinical trials.\u0000 \u0000 \u0000 \u0000 Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, EMBASE, MEDLINE, CINAHL via EBSCO, and Web of Science, completed 22nd Jan 22). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes grouped under standardised outcome terms. These were classified using the taxonomy proposed by the ‘Core Outcome Measures in Effectiveness Trials’ (COMET) initiative.\u0000 \u0000 \u0000 \u0000 Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: phase 2 n=33, phase 3 n=14. Common interventions included: surgery n=13, radiotherapy n=8, and pharmacotherapy n=20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardised outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas.\u0000 \u0000 \u0000 \u0000 Outcome measurement across meningioma clinical trials is heterogeneous. The standardised outcome terms identified will be prioritised through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set (COS) for use in future meningioma clinical trials.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"17 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140081995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Mikic, N. Gentilal, Fang Cao, E. Lok, Eric T Wong, M. Ballo, M. Glas, Pedro C Miranda, Axel Thielscher, A. Korshoej
{"title":"Tumor-Treating Fields Dosimetry in Glioblastoma: Insights into Treatment Planning, Optimization, and Dose-Response Relationships","authors":"N. Mikic, N. Gentilal, Fang Cao, E. Lok, Eric T Wong, M. Ballo, M. Glas, Pedro C Miranda, Axel Thielscher, A. Korshoej","doi":"10.1093/noajnl/vdae032","DOIUrl":"https://doi.org/10.1093/noajnl/vdae032","url":null,"abstract":"\u0000 Tumor Treating Fields (TTFields) is currently a Category 1A treatment recommendation by the U.S. National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action of TTFields has been partly elucidated, tangible and standardized metrics are lacking to assess anti-tumor dose and effects of the treatment. This paper outlines and evaluates the current standards and methodologies in the estimation of the TTFields distribution and dose measurement in the brain and highlights the most important principles governing TTFields dosimetry. The focus is on clinical utility to facilitate a practical understanding of these principles and how they can be used to guide treatment.\u0000 The current evidence for a correlation between TTFields dose, tumor growth, and clinical outcome will be presented and discussed. Furthermore, we will provide perspectives and updated insights into the planning and optimization of TTFields therapy for glioblastoma by reviewing how the dose and thermal effects of TTFields are affected by factors such as tumor location and morphology, peritumoral edema, electrode array position, treatment duration (compliance), array “edge effect”, electrical duty cycle, and skull-remodeling surgery.\u0000 Finally, perspectives are provided on how to optimize the efficacy of future TTFields therapy.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"32 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140081527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Cioffi, K. Waite, Mantas Dmukauskas, M. Glantz, Sonikpreet Aulakh, Theodore Nicolaides, S. Sengupta, Joanne Xiu, J. Barnholtz-Sloan
{"title":"Sex Differences in Glioblastoma Response to Treatment: Impact of MGMT Methylation","authors":"G. Cioffi, K. Waite, Mantas Dmukauskas, M. Glantz, Sonikpreet Aulakh, Theodore Nicolaides, S. Sengupta, Joanne Xiu, J. Barnholtz-Sloan","doi":"10.1093/noajnl/vdae031","DOIUrl":"https://doi.org/10.1093/noajnl/vdae031","url":null,"abstract":"","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"15 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140083942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne E M Leenders, Eva Kremer - Hooft van Huijsduijnen, Bruno Robalo, Rosa van Male, A. De Luca, Rachèl Kemps, E. Hoving, Maarten H Lequin, M. Grootenhuis, M. Partanen
{"title":"Unraveling the relations between post-traumatic stress symptoms, neurocognitive functioning and limbic white matter in pediatric brain tumor patients","authors":"Anne E M Leenders, Eva Kremer - Hooft van Huijsduijnen, Bruno Robalo, Rosa van Male, A. De Luca, Rachèl Kemps, E. Hoving, Maarten H Lequin, M. Grootenhuis, M. Partanen","doi":"10.1093/noajnl/vdae026","DOIUrl":"https://doi.org/10.1093/noajnl/vdae026","url":null,"abstract":"\u0000 \u0000 \u0000 Pediatric brain tumor patients are at risk of developing neurocognitive impairments and associated white matter alterations. In other populations, post-traumatic stress symptoms (PTSS) impact cognition and white matter. This study aims to investigate the effect of PTSS on neurocognitive functioning and limbic white matter in pediatric brain tumor patients.\u0000 \u0000 \u0000 \u0000 Sixty-six patients (6-16 years) completed neuropsychological assessment and brain MRI (one-year post-diagnosis) and parents completed PTSS proxy questionnaires (CRIES-13; 1-3 months and one-year post-diagnosis). Mean Z-scores and percentage impaired (>1SD) for attention, processing speed, executive functioning, and memory were compared to normscores (t-tests, chi-square tests). Multi-shell diffusion MRI data were analyzed for white matter tractography (fractional anisotropy/axial diffusivity). Effects of PTSS on neurocognition and white matter were explored with linear regression models (FDR correction for multiple testing), including age at diagnosis, treatment intensity, and tumor location as covariates. Neurocognition and limbic white matter associations were explored with correlations.\u0000 \u0000 \u0000 \u0000 Attention (M=-.49, 33% impaired; P<.05) and processing speed (M=-.57, 34% impaired; P<.05) were significantly lower than healthy peers. PTSS was associated with poorer processing speed (β=-0.64, P<.01). Treatment intensity, age at diagnosis, and tumor location, but not PTSS, were associated with limbic white matter metrics. Neurocognition and white matter metrics were not associated.\u0000 \u0000 \u0000 \u0000 Higher PTSS was associated with poorer processing speed, highlighting the need for monitoring and timely referrals to optimize psychological well-being and neurocognitive functioning. Future research should focus on longitudinal follow-up and explore the impact of PTSS interventions on neurocognitive performance.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"23 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Prezelski, D. G. Hsu, L.A. del Balzo, Erica Heller, Jennifer Ma, Luke R G Pike, A. Ballangrud, M. Aristophanous
{"title":"Artificial intelligence-driven measurements of brain metastases’ response to SRS compare favorably with current manual standards of assessment","authors":"K. Prezelski, D. G. Hsu, L.A. del Balzo, Erica Heller, Jennifer Ma, Luke R G Pike, A. Ballangrud, M. Aristophanous","doi":"10.1093/noajnl/vdae015","DOIUrl":"https://doi.org/10.1093/noajnl/vdae015","url":null,"abstract":"\u0000 \u0000 \u0000 Evaluation of treatment response for brain metastases (BMs) following stereotactic radiosurgery (SRS) becomes complex as the number of treated BMs increases. This study uses artificial intelligence (AI) to track BMs after SRS and validates its output compared with manual measurements.\u0000 \u0000 \u0000 \u0000 Patients with BMs who received at least one course of SRS and followed up with MRI scans were retrospectively identified. A tool for automated detection, segmentation, and tracking of intracranial metastases on longitudinal imaging, MEtastasis Tracking with Repeated Observations (METRO), was applied to the dataset. The longest three-dimensional (3D) diameter identified with METRO was compared with manual measurements of maximum axial BM diameter, and their correlation was analyzed. Change in size of the measured BM identified with METRO after SRS treatment was used to classify BMs as responding, or not responding, to treatment, and its accuracy was determined relative to manual measurements.\u0000 \u0000 \u0000 \u0000 From 71 patients, 176 BMs were identified and measured with METRO and manual methods. Based on a one-to-one correlation analysis, the correlation coefficient was R2 = 0.76 (p = 0.0001). Using modified BM response classifications of BM change in size, the longest 3D diameter data identified with METRO had a sensitivity of 0.72 and a specificity of 0.95 in identifying lesions that responded to SRS, when using manual axial diameter measurements as the ground truth.\u0000 \u0000 \u0000 \u0000 Using AI to automatically measure and track BM volumes following SRS treatment, this study showed a strong correlation between AI-driven measurements and the current clinically used method: manual axial diameter measurements.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"3 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}