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: Dhaenens, Britt A. E., Heimann, Guenter, Bakker, Annette, Nievo, Marco, Ferner, Rosalie E., Evans, D. Gareth, Wolkenstein, Pierre, Leubner, Jonas, Potratz, Cornelia, Carton, Charlotte, Iloeje, Uchenna, Kirk, George, Blakeley, Jaishri O., Plotkin, Scott, Fisher, Michael J., Kim, Aerang, Driever, Pablo Hernaiz, Azizi, Amedeo A., Widemann, Brigitte C., Gross, Andrea, Parke, Tom, Legius, Eric, Oostenbrink, Rianne

المصدر: Dhaenens , B A E , Heimann , G , Bakker , A , Nievo , M , Ferner , R E , Evans , D G , Wolkenstein , P , Leubner , J , Potratz , C , Carton , C , Iloeje , U , Kirk , G , Blakeley , J O , Plotkin , S , Fisher , M J , Kim , A , Driever , P H , Azizi , A A , Widemann , B C , Gross , A , Parke , T , Legius , E & Oostenbrink , ....

الوصف: Background Neurofibromatosis type 1, NF2-related schwannomatosis and non-NF2-related schwannomatosis (grouped under the abbreviation "NF") are rare hereditary tumor predisposition syndromes. Due to the low prevalence, variability in the range, and severity of manifestations, as well as limited treatment options, these conditions require innovative trial designs to accelerate the development of new treatments.Methods Within European Patient-Centric Clinical Trial Platforms (EU-PEARL), we designed 2 platform-basket trials in NF. The trials were designed by a team of multidisciplinary NF experts and trial methodology experts.Results The trial will consist of an observational and a treatment period. The observational period will serve as a longitudinal natural history study. The platform trial design and randomization to a sequence of available interventions allow for the addition of interventions during the trial. If a drug does not meet the predetermined efficacy endpoint or reveals unacceptable toxicities, participants may stop treatment on that arm and re-enter the observational period, where they can be re-randomized to a different treatment arm if eligible. Intervention-specific eligibility criteria and endpoints are listed in intervention-specific-appendices, allowing the flexibility and adaptability needed for highly variable and rare conditions like NF.Conclusions These innovative platform-basket trials for NF may serve as a model for other rare diseases, as they will enhance the chance of identifying beneficial treatments through optimal learning from a small number of patients. The goal of these trials is to identify beneficial treatments for NF more rapidly and at a lower cost than traditional, single-agent clinical trials.

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/d4a21425-c0df-4db6-ae17-09111a025a04Test

الإتاحة: https://doi.org/10.1093/nop/npae001Test
https://pure.eur.nl/en/publications/d4a21425-c0df-4db6-ae17-09111a025a04Test
https://pure.eur.nl/ws/files/135612928/npae001.pdfTest
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=eur_pure&SrcAuth=WosAPI&KeyUT=WOS:001152283100001&DestLinkType=FullRecord&DestApp=WOSTest

المؤلفون: Peltonen, Sirkku, Serup, Jørgen, Tang, Mimmi, Gillstedt, Martin, Kantere, Despoina, Neittaanmäki, Noora, Holmström, Peter, Blakeley, Jaishri O., Rosner, Karli, Roberts, Joshua, Bove, Torsten, Karmisholt, Katrine Elisabeth

المصدر: JEADV Clinical Practice ; ISSN 2768-6566 2768-6566

الوصف: Background High‐intensity focused ultrasound (HIFU) is widely used in the treatment of deep tumours, but clinical trials on skin tumours are not yet available. Neurofibromatosis Type I (NF1) is among the most common single‐gene inherited conditions worldwide and predisposes to benign and malignant neoplasms of the nervous system. Multiple cutaneous neurofibromas (cNFs) often cause social and functional limitations, itching and pain. Objectives The objective of this study was to investigate the safety, local tolerability and efficacy of a novel method utilizing HIFU for the treatment of cNFs. Methods A 20 MHz HIFU‐device with an integrated dermoscopic guidance and a handpiece with a focus depth of 2.3 mm below the skin surface was used. Doses of acoustic energy with 0.7 J/dose and pulse duration of 250 ms/dose were manually positioned with 1–2 mm distance between each applied dose. Number of applied doses depended on the size of the cNF. No anaesthetic was applied. Results Twenty patients with NF1 were recruited in two centres, and 147 cNFs were treated. There were no serious adverse events. Immediate and transient wheal‐and‐flare reactions occurred at treatment sites and occasionally there was minor epidermal damage which healed in 1–2 weeks. Dyspigmentation occurred in some tumours after 3–9 months but no scarring was observed at 9‐month follow‐up. During treatment, the patient‐reported pain‐score median was 3.5 (range 1–7) on a 0–10‐point scale. Clinical rating of cNFs after 9 months showed 48.9% full or major tumour reduction. The median reduction in tumour thickness measured by ultrasound at 9 months was 0.53 mm (range: –100% to +19%). Conclusions HIFU treatment is a new noninvasive, rapid and tolerable treatment modality that with high precision targets intradermal lesions. This study demonstrates acceptable safety, local tolerance and efficacy of HIFU for the treatment of cNFs that may further be developed also for other skin tumours.

الإتاحة: https://doi.org/10.1002/jvc2.398Test

المؤلفون: Zhou, Jinyuan, Zaiss, Moritz, Knutsson, Linda, Sun, Phillip Zhe, Ahn, Sung Soo, Aime, Silvio, Bachert, Peter, Blakeley, Jaishri O, Cai, Kejia, Chappell, Michael A, Chen, Min, Gochberg, Daniel F, Goerke, Steffen, Heo, Hye-Young, Jiang, Shanshan, Jin, Tao, Kim, Seong-Gi, Laterra, John, Paech, Daniel, Pagel, Mark D, Park, Ji Eun, Reddy, Ravinder, Sakata, Akihiko, Sartoretti-Schefer, Sabine, Sherry, A Dean, Smith, Seth A, Stanisz, Greg J, Sundgren, Pia C, Togao, Osamu, Vandsburger, Moriel, Wen, Zhibo, Wu, Yin, Zhang, Yi, Zhu, Wenzhen, Zu, Zhongliang, van Zijl, Peter C M

المصدر: Magnetic Resonance in Medicine MultiPark: Multidisciplinary research focused on Parkinson´s disease. 88(2):546-574

مصطلحات موضوعية: Naturvetenskap, Fysik, Annan fysik, Natural Sciences, Physical Sciences, Other Physics Topics, Medicin och hälsovetenskap, Klinisk medicin, Radiologi och bildbehandling, Medical and Health Sciences, Clinical Medicine, Radiology, Nuclear Medicine and Medical Imaging

الوصف: Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.

الوصول الحر: https://lup.lub.lu.se/record/0c9ba513-d295-4d67-8bba-6e94548217dfTest
http://dx.doi.org/10.1002/mrm.29241Test

المؤلفون: Plotkin, Scott R, Allen, Jeffrey, Dhall, Girish, Campian, Jian L, Clapp, D Wade, Fisher, Michael J, Jain, Rakesh K, Tonsgard, James, Ullrich, Nicole J, Thomas, Coretta, Edwards, Lloyd J, Korf, Bruce, Packer, Roger, Karajannis, Matthias A, Blakeley, Jaishri O

المساهمون: Dana-Farber/Harvard Cancer Center, Department of Defense

المصدر: Neuro-Oncology ; volume 25, issue 8, page 1498-1506 ; ISSN 1522-8517 1523-5866

الوصف: Background Prospective data on maintenance therapy with bevacizumab for persons with NF2-related schwannomatosis (NF2-SWN) is lacking. In this prospective multicenter phase II study, we evaluated the efficacy, safety, and tolerability of bevacizumab for maintenance therapy in children and adults with NF2-SWN and hearing loss due to vestibular schwannomas (VS). Methods Following induction therapy, participants received bevacizumab 5 mg/kg every 3 weeks for 18 months. Participants were monitored for changes in hearing, tumor size, and quality of life (QOL), and for adverse events. Hearing loss was defined as a statistically significant decline in word recognition score (WRS) or pure-tone average compared to the study baseline; tumor growth was defined as >20% increase in volume compared to baseline. Results Twenty participants with NF2-SWN (median age 23.5 years; range, 12.5–62.5 years) with hearing loss in the target ear (median WRS 70%, range 2%–94%) received maintenance bevacizumab. Freedom from hearing loss in the target ear was 95% after 48 weeks, 89% after 72 weeks, and 70% after 98 weeks. Freedom from tumor growth in the target VS was 94% after 48 weeks, 89% after 72 weeks, and 89% after 98 weeks. NF2-related QOL remained stable for 98 weeks whereas tinnitus-related distress decreased. Maintenance bevacizumab was well tolerated, with 3 participants (15%) discontinuing treatment due to adverse events. Conclusions Maintenance bevacizumab (5 mg/kg every 3 weeks) is associated with high rates of hearing and tumor stability during 18 months of follow-up. No new unexpected adverse events related to bevacizumab were identified in this population.

الإتاحة: https://doi.org/10.1093/neuonc/noad066Test
https://academic.oup.com/neuro-oncology/article-pdf/25/8/1498/51031031/noad066.pdfTest

المؤلفون: Zhang, Lindy, Lemberg, Kathryn M, Calizo, Ana, Varadhan, Ravi, Siegel, Alan H, Meyer, Christian F, Blakeley, Jaishri O, Pratilas, Christine A

المصدر: Neuro-Oncology Advances ; volume 5, issue 1 ; ISSN 2632-2498

مصطلحات موضوعية: Surgery, Oncology, Neurology (clinical)

الوصف: Background Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas originating from cellular components within the nerve sheath. The incidence of MPNST is highest in people with neurofibromatosis type 1 (NF1), and MPNST is the leading cause of death for these individuals. Complete surgical resection is the only curative therapeutic option, but is often unfeasible due to tumor location, size, or presence of metastases. Evidence-based choices of chemotherapy for recurrent/refractory MPNST remain elusive. To address this gap, we conducted a retrospective analysis of our institutional experience in treating patients with relapsed MPNST in order to describe patient outcomes related to salvage regimens. Methods We conducted a retrospective electronic health record analysis of patients with MPNST who were treated at Johns Hopkins Hospital from January 2010 to June 2021. We calculated time to progression (TTP) based on salvage chemotherapy regimens. Results Sixty-five patients were included in the analysis. Upfront therapy included single or combined modalities of surgery, chemotherapy, or radiotherapy. Forty-eight patients received at least 1 line of chemotherapy, which included 23 different regimens (excluding active clinical studies). Most patients (n = 42, 87.5%) received a combination of doxorubicin, ifosfamide, or etoposide as first-line chemotherapy. Salvage chemotherapy regimens and their TTP varied greatly, with irinotecan/temozolomide-based regimens having the longest average TTP (255.5 days, among 4 patients). Conclusions Patients with advanced or metastatic MPNST often succumb to their disease despite multiple lines of therapy. These data may be used as comparative information in decision-making for future patients and clinical trials.

الإتاحة: https://doi.org/10.1093/noajnl/vdad156Test
https://academic.oup.com/noa/article-pdf/5/1/vdad156/54715972/vdad156.pdfTest

المؤلفون: Banerjee, Jineta, Friedman, Jan M., Klesse, Laura J., Yohay, Kaleb H., Jordan, Justin T., Plotkin, Scott R., Allaway, Robert J., Blakeley, Jaishri O.

المصدر: Genetics in Medicine ; volume 25, issue 2, page 100324 ; ISSN 1098-3600

مصطلحات موضوعية: Genetics (clinical)

الإتاحة: https://doi.org/10.1016/j.gim.2022.10.007Test
https://api.elsevier.com/content/article/PII:S1098360022009881?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1098360022009881?httpAccept=text/plainTest