المؤلفون: Blakeley, Jaishri O, Le, Lu Q, Lee, Sang Y, Ly, Ina, Rhodes, Steven D, Romo, Carlos G, Sarin, Kavita Y, Staedtke, Verena, Steensma, Matthew R, Wolkenstein, Pierre, Participants, 2022 NTAP Cutaneous Neurofibroma Symposium, Largaespada, David, Serra, Eduard, Haniffa, Muzlifah, Bakker, Annette, McCormick, Frank, Cagan, Ross L, Ju, William, Stemmer-Rachamimov, Anat, Grimes, Kevin, Topilko, Piotr, Kornacki, Deanna, Kelly, Kristen M, Gottesman, Sally, York, Zachary, Epps, Roselyn

المصدر: Journal of Investigative Dermatology. 143(8)

مصطلحات موضوعية: Humans, Neurofibroma, Neurofibromatosis 1, Skin Neoplasms, Connective Tissue Diseases, NTAP Cutaneous Neurofibroma Symposium Participants, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7cs8b3d4Test

المؤلفون: Li, Yingjoy, Blakeley, Jaishri O, Ly, Ina, Berman, Yemima, Lau, Jonathan, Wolkenstein, Pierre, Bergqvist, Christina, Jia, Wangcun, Milner, Thomas E, Katta, Nitesh, Durkin, Anthony J, Kennedy, Gordon T, Rowland, Rebecca, Romo, Carlos G, Fleming, Jane, Kelly, Kristen M

المصدر: Journal of Investigative Dermatology. 143(8)

مصطلحات موضوعية: Cancer, Rare Diseases, Biomedical Imaging, Neurosciences, Neurofibromatosis, Pediatric, Humans, Neurofibromatosis 1, Neurofibroma, Skin Neoplasms, Ultrasonography, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases

الوصف: A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4qg8h655Test

المؤلفون: Ly, Ina, Romo, Carlos G, Gottesman, Sally, Kelly, Kristen M, Kornacki, Deanna, York, Zachary, Lee, Sang Y, Rhodes, Steven D, Staedtke, Verena, Steensma, Matthew R, Blakeley, Jaishri O, Wolkenstein, Pierre

المصدر: The Journal of investigative dermatology. 143(8)

مصطلحات موضوعية: Humans, Neurofibroma, Neurofibromatosis 1, Skin Neoplasms, Pruritus, Quality of Life, Adult, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Rare Diseases, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases

الوصف: Cutaneous neurofibromas (cNFs) are benign tumors of the skin that affect >95% of adults with neurofibromatosis type 1. Despite their benign histology, cNFs can significantly impact QOL due to disfigurement, pain, and pruritus. There are no approved therapies for cNFs. Existing treatments are limited to surgery or laser-based treatments that have had mixed success and cannot be readily applied to a large number of tumors. We review cNF treatment options that are currently available and under investigation, discuss the regulatory considerations specific to cNFs, and propose strategies to improve cNF clinical trial design and standardize clinical trial endpoints.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2j02s0htTest

المؤلفون: de Blank, Peter MK, Gross, Andrea M, Akshintala, Srivandana, Blakeley, Jaishri O, Bollag, Gideon, Cannon, Ashley, Dombi, Eva, Fangusaro, Jason, Gelb, Bruce D, Hargrave, Darren, Kim, AeRang, Klesse, Laura J, Loh, Mignon, Martin, Staci, Moertel, Christopher, Packer, Roger, Payne, Jonathan M, Rauen, Katherine A, Rios, Jonathan J, Robison, Nathan, Schorry, Elizabeth K, Shannon, Kevin, Stevenson, David A, Stieglitz, Elliot, Ullrich, Nicole J, Walsh, Karin S, Weiss, Brian D, Wolters, Pamela L, Yohay, Kaleb, Yohe, Marielle E, Widemann, Brigitte C, Fisher, Michael J

المصدر: Neuro-Oncology. 24(11)

مصطلحات موضوعية: Neurosciences, Neurofibromatosis, Rare Diseases, Cancer, Pediatric, Child, Humans, Consensus, Mitogen-Activated Protein Kinase Kinases, Neurofibroma, Plexiform, Neurofibromatosis 1, Protein Kinase Inhibitors, low-grade glioma, MEK inhibitors, neurofibromatosis type 1, plexiform neurofibromas, RASopathy, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere. Several recently published and ongoing clinical trials have demonstrated that MEKi may have potential benefits for a variety of other NF1 manifestations, and there is broad interest in the field regarding the appropriate clinical use of these agents. In this review, we present the current evidence regarding the use of existing MEKi for a variety of NF1-related manifestations, including tumor (neurofibromas, malignant peripheral nerve sheath tumors, low-grade glioma, and juvenile myelomonocytic leukemia) and non-tumor (bone, pain, and neurocognitive) manifestations. We discuss the potential utility of MEKi in related genetic conditions characterized by overactivation of the RAS pathway (RASopathies). In addition, we review practical treatment considerations for the use of MEKi as well as provide consensus recommendations regarding their clinical use from a panel of experts.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/68v541w1Test

المؤلفون: Blakeley, Jaishri O, Bakker, Annette, Barker, Anne, Clapp, Wade, Ferner, Rosalie, Fisher, Michael J, Giovannini, Marco, Gutmann, David H, Karajannis, Matthias A, Kissil, Joseph L, Legius, Eric, Lloyd, Alison C, Packer, Roger J, Ramesh, Vijaya, Riccardi, Vincent M, Stevenson, David A, Ullrich, Nicole J, Upadhyaya, Meena, Stemmer‐Rachamimov, Anat

المصدر: American Journal of Medical Genetics Part A. 173(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Brain Disorders, Neurofibromatosis, Pediatric, Rare Diseases, Orphan Drug, Cancer, Pediatric Cancer, Pediatric Research Initiative, Neurosciences, Brain Cancer, Child, Humans, Neurilemmoma, Neurofibromatoses, Neurofibromatosis 1, Neurofibromatosis 2, Pediatrics, Skin Neoplasms, neurofibromatosis type 1, neurofibromatosis type 2, pediatric tumors, rare disease, schwannomatosis, therapeutic discovery, Genetics, Clinical Sciences, Clinical sciences

الوصف: The Annual Children's Tumor Foundation International Neurofibromatosis Meeting is the premier venue for connecting discovery, translational and clinical scientists who are focused on neurofibromatosis types 1 and 2 (NF1 and NF2) and schwannomatosis (SWN). The meeting also features rare tumors such as glioma, meningioma, sarcoma, and neuroblastoma that occur both within these syndromes and spontaneously; associated with somatic mutations in NF1, NF2, and SWN. The meeting addresses both state of the field for current clinical care as well as emerging preclinical models fueling discovery of new therapeutic targets and discovery science initiatives investigating mechanisms of tumorigenesis. Importantly, this conference is a forum for presenting work in progress and bringing together all stakeholders in the scientific community. A highlight of the conference was the involvement of scientists from the pharmaceutical industry who presented growing efforts for rare disease therapeutic development in general and specifically, in pediatric patients with rare tumor syndromes. Another highlight was the focus on new investigators who presented new data about biomarker discovery, tumor pathogenesis, and diagnostic tools for NF1, NF2, and SWN. This report summarizes the themes of the meeting and a synthesis of the scientific discoveries presented at the conference in order to make the larger research community aware of progress in the neurofibromatoses.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/32t721k9Test

المؤلفون: Ahlawat, Shivani, Fayad, Laura M, Khan, Muhammad Shayan, Bredella, Miriam A, Harris, Gordon J, Evans, D Gareth, Farschtschi, Said, Jacobs, Michael A, Chhabra, Avneesh, Salamon, Johannes M, Wenzel, Ralph, Mautner, Victor F, Dombi, Eva, Cai, Wenli, Plotkin, Scott R, Blakeley, Jaishri O

المصدر: Neurology. 87(7_Supplement_1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Neurofibromatosis, Clinical Research, Neurosciences, Rare Diseases, Biomedical Imaging, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Clinical Trials as Topic, Humans, Magnetic Resonance Imaging, Multicenter Studies as Topic, Neurilemmoma, Neurofibromatoses, Neurofibromatosis 1, Neurofibromatosis 2, Skin Neoplasms, Whole Body Imaging, Whole Body MRI Committee for the REiNS International Collaboration, REiNS International Collaboration Members 2016, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences

الوصف: ObjectivesThe Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration Whole-Body MRI (WB-MRI) Working Group reviewed the existing literature on WB-MRI, an emerging technology for assessing disease in patients with neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN), to recommend optimal image acquisition and analysis methods to enable WB-MRI as an endpoint in NF clinical trials.MethodsA systematic process was used to review all published data about WB-MRI in NF syndromes to assess diagnostic accuracy, feasibility and reproducibility, and data about specific techniques for assessment of tumor burden, characterization of neoplasms, and response to therapy.ResultsWB-MRI at 1.5T or 3.0T is feasible for image acquisition. Short tau inversion recovery (STIR) sequence is used in all investigations to date, suggesting consensus about the utility of this sequence for detection of WB tumor burden in people with NF. There are insufficient data to support a consensus statement about the optimal imaging planes (axial vs coronal) or 2D vs 3D approaches. Functional imaging, although used in some NF studies, has not been systematically applied or evaluated. There are no comparative studies between regional vs WB-MRI or evaluations of WB-MRI reproducibility.ConclusionsWB-MRI is feasible for identifying tumors using both 1.5T and 3.0T systems. The STIR sequence is a core sequence. Additional investigation is needed to define the optimal approach for volumetric analysis, the reproducibility of WB-MRI in NF, and the diagnostic performance of WB-MRI vs regional MRI.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9fk3x4pzTest

المؤلفون: Hanemann, C Oliver, Blakeley, Jaishri O, Nunes, Fabio P, Robertson, Kent, Stemmer-Rachamimov, Anat, Mautner, Victor, Kurtz, Andreas, Ferguson, Michael, Widemann, Brigitte C, Evans, D Gareth, Ferner, Rosalie, Carroll, Steven L, Korf, Bruce, Wolkenstein, Pierre, Knight, Pamela, Plotkin, Scott R

المصدر: Neurology. 87(7_Supplement_1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Neurofibromatosis, Pediatric, Neurosciences, Biological Specimen Banks, Biomarkers, Datasets as Topic, Humans, Neurilemmoma, Neurofibromatoses, Neurofibromatosis 1, Neurofibromatosis 2, Skin Neoplasms, REiNS International Collaboration, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences

الوصف: ObjectiveClinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group's goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs).MethodsThe biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF, and developed recommendations in a series of consensus meetings.ResultsWe describe existing biomarkers in NF and report consensus recommendations for SOP and a minimal clinical dataset to accompany samples derived from patients with NF1, NF2, and SWN in decentralized biobanks.ConclusionsThese recommendations are intended to provide clinicians and researchers with a common set of guidelines to collect and store biospecimens and for establishment of biobanks for NF1, NF2, and SWN.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7rb006h8Test

المؤلفون: Plotkin, Scott R, Davis, Stephanie D, Robertson, Kent A, Akshintala, Srivandana, Allen, Julian, Fisher, Michael J, Blakeley, Jaishri O, Widemann, Brigitte C, Ferner, Rosalie E, Marcus, Carole L

المصدر: Neurology. 87(7_Supplement_1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Lung, Neurosciences, Rare Diseases, Neurofibromatosis, Clinical Trials and Supportive Activities, Sleep Research, Respiratory, Clinical Trials as Topic, Humans, Neurofibroma, Plexiform, Neurofibromatosis 1, Oscillometry, Polysomnography, Sleep, Spirometry, Treatment Outcome, REiNS International Collaboration, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences

الوصف: ObjectivePlexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN.MethodsThe Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials.ResultsFor patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows.ConclusionsThese recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2w3294qdTest

المؤلفون: Wang, Xia, Kallionpää, Roope A, Gonzales, Patrick R, Chitale, Dhananjay A, Tousignant, Renee N, Crowley, Jacob P, Chen, Zhihua, Yoder, Sean J, Blakeley, Jaishri O, Acosta, Maria T, Korf, Bruce R, Messiaen, Ludwine M, Tainsky, Michael A

المصدر: Pathology and Laboratory Medicine Articles

مصطلحات موضوعية: Breast Neoplasms, Cyclin-Dependent Kinase 4, DNA Mutational Analysis, Datasets as Topic, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Loss of Heterozygosity, Neurofibromatosis 1, Neurofibromin 1, Receptor, ErbB-2

الوصف: NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histologic characteristics of these breast cancers, we analyzed the tumors with NF1 germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neurofibromatosis type 1 (NF1), 9 samples (NF + BrCa) underwent genomic copy number (CN) and targeted sequencing analysis. Mutations of NF1 were identified in two samples and TP53 were in three. No mutation was detected in ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, and STK11 HER2 (ErbB2) overexpression was detected by IHC in 69.2% (9/13) of the tumors. CN gain/amplification of ERBB2 was detected in 4 of 9 with DNA analysis. By evaluating HER2 expression and NF1 alterations in unselected invasive breast cancers in TCGA datasets, we discovered that among samples with ERBB2 CN gain/amplification, the HER2 mRNA and protein expression were much more pronounced in NF1-mutated/deleted samples in comparison with NF1-unaltered samples. This finding suggests a synergistic interplay between these two genes, potentially driving the development of breast cancer harboring NF1 mutation and ERBB2 CN gain/amplification. NF1 gene loss of heterozygosity was observed in 4 of 9 NF + BrCa samples. CDK4 appeared to have more CN gain in NF + BrCa and exhibited increased mRNA expression in TCGA NF1--altered samples.

العلاقة: https://scholarlycommons.henryford.com/pathology_articles/176Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:30104415Test

الإتاحة: https://scholarlycommons.henryford.com/pathology_articles/176Test
http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:30104415Test

المؤلفون: Dirven, Linda, Armstrong, Terri S, Blakeley, Jaishri O, Brown, Paul D, Grant, Robin, Jalali, Rakesh, Leeper, Heather, Mendoza, Tito, Nayak, Lakshmi, Reijneveld, Jaap C, Le Rhun, Emilie, Walbert, Tobias, Weller, Michael, Wen, Patrick Y, Taphoorn, Martin JB

المصدر: Neurosurgery Articles

مصطلحات موضوعية: Brain Neoplasms, Cooperative Behavior, Humans, Interdisciplinary Communication, International Cooperation, Medical Oncology, Neurology, Outcome and Process Assessment (Health Care), Patient Reported Outcome Measures, Treatment Outcome

الوصف: The Response Assessment in Neuro-Oncology-Patient-Reported Outcome (RANO-PRO) working group is an international multidisciplinary collaboration that provides guidance on the use of patient-reported outcome (PRO) measures in clinical trials and practice for adult patients with brain tumours. Findings from both PROs and traditional outcome measures, such as survival, and clinical or radiological response, are essential to inform the research community, policy makers, physicians, and patients in the treatment decision-making process. Previous initiatives in oncology have focused on guidelines concerning the collection, analysis, interpretation, and reporting of PRO data. However, we recommend the application of appropriate PRO instruments, with respect to its content and measurement properties (ie, research question, content validity, and other measurement properties), in brain tumour research. PROs should be well defined and reliable to generate high-quality evidence, and our recommendations on the use of specific PRO measures could help to improve the quality of PRO evidence derived from neuro-oncological studies, and might add a new dimension in how the value of therapeutics is assessed in patients with brain tumours. In this Policy Review, we present the RANO-PRO working plan for the use of PROs in adults with brain tumours.

العلاقة: https://scholarlycommons.henryford.com/neurosurgery_articles/93Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:29508764Test

الإتاحة: https://scholarlycommons.henryford.com/neurosurgery_articles/93Test
http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:29508764Test