المؤلفون: Miller, Julie J, Gonzalez Castro, L Nicolas, McBrayer, Samuel, Weller, Michael, Cloughesy, Timothy, Portnow, Jana, Andronesi, Ovidiu, Barnholtz-Sloan, Jill S, Baumert, Brigitta G, Berger, Mitchell S, Bi, Wenya Linda, Bindra, Ranjit, Cahill, Daniel P, Chang, Susan M, Costello, Joseph F, Horbinski, Craig, Huang, Raymond Y, Jenkins, Robert B, Ligon, Keith L, Mellinghoff, Ingo K, Nabors, L Burt, Platten, Michael, Reardon, David A, Shi, Diana D, Schiff, David, Wick, Wolfgang, Yan, Hai, von Deimling, Andreas, van den Bent, Martin, Kaelin, William G, Wen, Patrick Y

المصدر: Neuro-Oncology ; volume 25, issue 1, page 4-25 ; ISSN 1522-8517 1523-5866

الوصف: Isocitrate dehydrogenase (IDH) mutant gliomas are the most common adult, malignant primary brain tumors diagnosed in patients younger than 50, constituting an important cause of morbidity and mortality. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors, sparking multiple efforts to improve their diagnosis and treatment. In this consensus review from the Society for Neuro-Oncology (SNO), the current diagnosis and management of IDH-mutant gliomas will be discussed. In addition, novel therapies, such as targeted molecular therapies and immunotherapies, will be reviewed. Current challenges and future directions for research will be discussed.

الإتاحة: https://doi.org/10.1093/neuonc/noac207Test
https://academic.oup.com/neuro-oncology/article-pdf/25/1/4/48496899/noac207.pdfTest

المؤلفون: Miller, Alexandra, Ramamurthy, Bhaskar, Pike, Luke, Keralapura, Mallika, Hofius, Jonathan, Marshall, Jack, Jones, Marvin, Lee, Chi-Yin, Stember, Joseph, Brennan, Cameron, Kaley, Thomas, Dittamore, Ryan, Mellinghoff, Ingo

المصدر: Neuro-Oncology ; volume 24, issue Supplement_7, page vii87-vii88 ; ISSN 1522-8517 1523-5866

الوصف: The WHO recommends molecular characterization of CNS tumors. (Louis et al., 2021, 2016). However, many patients at diagnosis and recurrence, do not have tissue accessible for genomics. Blood-based liquid biopsy tests, provide a non-invasive means to obtain genomic data. Liquid biopsy tests are widely adopted to avoid side effects related to invasive biopsies in other solid tumors. However, for primary brain tumors, most patients have cfDNA concentrations below the Limit-of-Detection (LOD) of the tests. The primary contributor to low yield is the blood-brain barrier (BBB) which prevents free passage of tumor analytes into the circulatory system. BBB opening mediated by Focused Ultrasound (FUS) oscillation of microbubbles (MB) has led to an increase of tumor-derived circulating biomarkers in pre-clinical models and in human GBM (Zhu et al 2018, Meng et al 2021). Cordance Medical is developing a non-invasive, portable FUS platform that can enable clinic-based BBB opening treatments. The Cordance device utilizes three transducer types, a Type 1 transducer for non-invasive BBB opening localization obtains Doppler images of the Circle-of-Willis through the temporal lobe. The Doppler images align to the existing MRI using CoW as the fiducial. An array of Type 2 transducers for BBB opening to generate sufficient acoustic pressure to safely oscillate MBs to open the BBB. Finally, Type 3 transducers for safety monitoring receive echo signals from the MBs. Signals are analyzed for harmonic content which enables safety monitoring. The primary endpoint, we will be examining the Cordance platform's ability to increase the concentration of circulating biomarkers following a safe BBB opening. We will recruit patients with recurrent GBM. Patients will receive a baseline blood draw, a BBB opening treatment with the Cordance device, followed by a blood draw after the treatment. Liquid biopsy tests to be examined include the MSK ACCESS test and tumor-informed ddPCR MRD test.

الإتاحة: https://doi.org/10.1093/neuonc/noac209.329Test
https://academic.oup.com/neuro-oncology/article-pdf/24/Supplement_7/vii87/47019325/noac209.329.pdfTest

المؤلفون: Kushnirsky, Marina, Thakur, Sunitha, Karajannis, Matthias, Bale, Tejus, Rosenblum, Marc, Malani, Rachna, Gavrilovic, Igor T, Schaff, Lauren, Pentsova, Elena, Grommes, Christian, Moss, Nelson, Sait, Sameer Farouk, Hill, Katherine, Miller, Alexandra, Mellinghoff, Ingo, Young, Robert, Lin, Andrew

المصدر: Neuro-Oncology ; volume 24, issue Supplement_7, page vii176-vii177 ; ISSN 1522-8517 1523-5866

مصطلحات موضوعية: Cancer Research, Neurology (clinical), Oncology

الوصف: INTRODUCTION Treatment of brainstem tumors is often initiated without a tissue diagnosis due to the risk of biopsy. A subset of brainstem gliomas harbor an isocitrate dehydrogenase 1/2 (IDH) mutation, which predicts response to alkylator chemotherapy and IDH inhibitors; non-invasive diagnostic tests are needed to identify these mutations. METHODS We identified a cohort of patients with IDH-mutant brainstem gliomas through chart review of patients who underwent magnetic resonance spectroscopy (MRS) and/or brain biopsy. IDH mutation was established by biopsy, presence of a 2-hydroxyglutarate (2HG) peak on MRS, or identification on cerebrospinal fluid (CSF) sequencing of cell-free DNA (cfDNA). RESULTS We identified 15 patients with IDH-mutant brainstem gliomas, age range 5-48, 47% women. 15/15 were involving/abutting the brachium pontis, and 10/15 were non-enhancing at diagnosis. 13/15 patients were identified by biopsy, 1/15 by MRS and CSF, and 1/15 by MRS only. 10/13 patients with available data had a non-IDH1 R132H mutation in IDH1/2. 7/7 patients with MRS prior to radiation had a 2HG peak (MRS was concordant with tissue in all cases in which biopsy was obtained). 4/6 patients with MRS post-radiation retained a 2HG peak. 4 IDH-mutant tumors had sequencing of cfDNA and an IDH mutation was found in 2/4. Response data was available in 13/15 patients; all received radiation, 10 with concurrent temozolomide: best response was partial response in 8 and stable disease in 5. 4 patients received an IDH inhibitor: 2 patients after progression, and 2 as maintenance after radiation/temozolomide, achieving tumor control in all. For this cohort, median PFS was 71.4 months and median OS has not been reached. CONCLUSION IDH-mutant brainstem gliomas have a characteristic appearance, a high response rate to treatment, and a better overall prognosis than other brainstem tumors. MRS and CSF cfDNA sequencing allow for non-invasive diagnosis of IDH mutations in these patients.

الإتاحة: https://doi.org/10.1093/neuonc/noac209.675Test
https://academic.oup.com/neuro-oncology/article-pdf/24/Supplement_7/vii176/47020924/noac209.675.pdfTest

المؤلفون: Buxton, Meredith, Alexander, Brian, Berry, Donald, Cavenee, Webster, Colman, Howard, de Groot, John, Ellingson, Benjamin, Gordon, Gary, Khasraw, Mustafa, Lassman, Andrew, Lee, Eudocia, Li, Wenbin, Lim, Michael, Mellinghoff, Ingo, Mikkelsen, Tom, Nelli, Apoorva, Perry, James, Sulman, Erik, Tanner, Kirk, Weller, Michael, Wen, Patrick Y, Alfred Yung, W K, Cloughesy, Timothy

المصدر: Neuro-Oncology ; volume 24, issue Supplement_7, page vii80-vii80 ; ISSN 1522-8517 1523-5866

مصطلحات موضوعية: Cancer Research, Neurology (clinical), Oncology

الوصف: BACKGROUND GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a biomarker based, multi-arm, international, seamless Phase 2/3 response adaptive randomization platform trial designed to rapidly identify experimental therapies that improve overall survival and confirm efficacious experimental therapies and associated biomarker signatures to support new drug approvals and registration. GBM AGILE is a collaboration between academic investigators, patient organizations and industry to support new drug applications for newly diagnosed and recurrent GBM. METHODS The primary objective of GBM AGILE is to identify therapies that effectively improve the overall survival in patients with ND or recurrent GBM. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to investigational arms based on their performance. Operating under a Master Protocol, GBM AGILE allows multiple drugs from different pharmaceutical/biotech companies to be evaluated simultaneously and/or over time against a common control. New experimental therapies are added as information about promising new drugs is identified while therapies are removed as they complete their evaluation. The master protocol/ trial infrastructure includes efficiencies through an adaptive trial design, shared control arm and operational processes to serve the goal of helping patients receive optimal care in a fast and efficient manner. GBM AGILE has screened over 1200 patients and enrollment rates are 3 to 4 times greater than traditional GBM trials, with active sites averaging 0.75 to 1 patients/sites/month. There are 41 active sites in the US, 4 active sites in Canada and 3 active sites in Europe with more sites anticipated to open across 5 countries in Europe. Expansion to China and Australia are under progress. Through the use of improved and flexible processes, GBM AGILE serves as a global trial that supports the efficient and rapid incorporation and evaluation of new experimental therapies ...

الإتاحة: https://doi.org/10.1093/neuonc/noac209.303Test
https://academic.oup.com/neuro-oncology/article-pdf/24/Supplement_7/vii80/47019231/noac209.303.pdfTest

المؤلفون: Piotrowski, Anna F., Campian, Jian L., Brown, Rebecca, Diarte, Jose, Rodriguez, Fausto, Bale, Tejus A., Dahiya, Sonika, Prichett, Laura, Mellinghoff, Ingo K., Blakeley, Jaishri O., Romo, Carlos G.

المصدر: Neurology ; volume 98, issue 18_supplement ; ISSN 0028-3878 1526-632X

الإتاحة: https://doi.org/10.1212/wnl.98.18_supplement.3261Test

المؤلفون: Schaff, Lauren R., Kushnirsky, Marina, Lin, Andrew L., Nandakumar, Subhiksha, Grommes, Christian, Miller, Alexandra Michelle, Gavrilovic, Igor T., Nolan, Craig, Pentsova, Elena, Mellinghoff, Ingo K., Kaley, Thomas J.

المصدر: Neurology ; volume 99, issue 17, page 750-755 ; ISSN 0028-3878 1526-632X

الإتاحة: https://doi.org/10.1212/wnl.0000000000201203Test

المؤلفون: Kushnirsky, Marina, Lin, Andrew, Miller, Alexandra, Gavrilovic, Igor, Nolan, Craig, Pentsova, Elena, Mellinghoff, Ingo, Kaley, Thomas, Schaff, Lauren

المصدر: Neurology ; volume 98, issue 18_supplement ; ISSN 0028-3878 1526-632X

الإتاحة: https://doi.org/10.1212/wnl.98.18_supplement.2219Test

المؤلفون: Rohle, Dan, Popovici-Muller, Janeta, Palaskas, Nicolaos, Turcan, Sevin, Grommes, Christian, Campos, Carl, Tsoi, Jennifer, Clark, Owen, Oldrini, Barbara, Komisopoulou, Evangelia, Kunii, Kaiko, Pedraza, Alicia, Schalm, Stefanie, Silverman, Lee, Miller, Alexandra, Wang, Fang, Yang, Hua, Chen, Yue, Kernytsky, Andrew, Rosenblum, Marc K., Liu, Wei, Biller, Scott A., Su, Shinsan M., Brennan, Cameron W., Chan, Timothy A., Graeber, Thomas G., Yen, Katharine E., Mellinghoff, Ingo K.

المصدر: Science, 2013 May 01. 340(6132), 626-630.

الوصول الحر: http://dx.doi.org/10.1126/science.1236062Test

المؤلفون: Morris, Luc G. T., Taylor, Barry S., Bivona, Trever G., Gong, Yongxing, Eng, Stephanie, Brennan, Cameron W., Kaufman, Andrew, Kastenhuber, Edward R., Banuchi, Victoria E., Singh, Bhuvanesh, Heguy, Adriana, Viale, Agnes, Mellinghoff, Ingo K., Huse, Jason, Ganly, Ian, Chan, Timothy A.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2011 Nov . 108(47), 19024-19029.

الوصول الحر: https://www.jstor.org/stable/23058642Test

المؤلفون: Mellinghoff, Ingo K., Touat, Mehdi, Maher, Elizabeth, DeLaFuente, Macarena, Cloughesy, Timothy F., Holdhoff, Matthias, Cote, Gregory, Burris, Howard, Janku, Filip, Huang, Raymond, Young, Robert, Ellingson, Benjamin, Auer, Julia, Liu, Hua, Hurov, Jonathan, Yen, Katherine, Agresta, Sam, Attar, Eyal, Pandya, Susan, Wen, Patrick Y.

المصدر: Neuro-Oncology ; volume 18, issue suppl_6, page vi12-vi12 ; ISSN 1522-8517 1523-5866

مصطلحات موضوعية: Cancer Research, Neurology (clinical), Oncology

الإتاحة: https://doi.org/10.1093/neuonc/now212.044Test
http://academic.oup.com/neuro-oncology/article-pdf/18/suppl_6/vi12/9645245/now212.044.pdfTest