Pitfalls in the Neuroimaging of Glioblastoma in the Era of Antiangiogenic and Immuno/Targeted Therapy – Detecting Illusive Disease, Defining Response
TLDR
In this article, a review of advanced imaging techniques including perfusion MRI, diffusion MRI, MR spectroscopy, and new PET imaging tracers are discussed in the context of determining response and progression during treatment of glioblastoma both in the standard care as well as clinical trial context.Abstract:
Glioblastoma, the most common malignant primary brain tumor in adults is a devastating diagnosis with an average survival of 14-16 months using the current standard of care treatment. The determination of treatment response and clinical decision making is based on the accuracy of radiographic assessment. Notwithstanding, challenges exist in the neuroimaging evaluation of patients undergoing treatment for malignant glioma. Differentiating treatment response from tumor progression is problematic and currently combines long-term follow-up using standard MRI, with clinical status and corticosteroid-dependency assessments. In the clinical trial setting, treatment with gene therapy, vaccines, immunotherapy, and targeted biologicals similarly produces MRI changes mimicking disease progression. A neuroimaging method to clearly distinguish between pseudoprogression and tumor progression has unfortunately not been found to date. With the incorporation of antiangiogenic therapies, a further pitfall in imaging interpretation is pseudoresponse. The Macdonald Criteria that correlate tumor burden with contrast enhanced imaging proved insufficient and misleading in the context of rapid blood brain barrier normalization following antiangiogenic treatment that is not accompanied by expected survival benefit. Even improved criteria, such as the RANO criteria, that incorporate non-enhancing disease, clinical status, and need for corticosteroid use, fall short of definitively distinguishing tumor progression, pseudoresponse, and pseudoprogression. This review focuses on advanced imaging techniques including perfusion MRI, diffusion MRI, MR spectroscopy, and new PET imaging tracers. The relevant image analysis algorithms and interpretation methods of these promising techniques are discussed in the context of determining response and progression during treatment of glioblastoma both in the standard of care as well as clinical trial context.read more
Citations
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The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
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Immunotherapy response assessment in neuro-oncology: a report of the RANO working group.
Hideho Okada,Michael Weller,Raymond Y. Huang,Gaetano Finocchiaro,Mark R. Gilbert,Wolfgang Wick,Benjamin M. Ellingson,Naoya Hashimoto,Ian F. Pollack,Alba A. Brandes,Enrico Franceschi,Christel Herold-Mende,Lakshmi Nayak,Ashok Panigrahy,Whitney B. Pope,Robert M. Prins,John H. Sampson,Patrick Y. Wen,David A. Reardon +18 more
TL;DR: Immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group are described.
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Multiplexed Profiling of Single Extracellular Vesicles.
Kyungheon Lee,Kyle B. Fraser,Bassel Ghaddar,Katy Yang,Eunha Kim,Leonora Balaj,E. Antonio Chiocca,Xandra O. Breakefield,Hakho Lee,Ralph Weissleder +9 more
TL;DR: A single EV analysis (SEA) technique which is simple, sensitive, multiplexable, and practical is described and the potential to address fundamental questions in vesicle biology and clinical applications is addressed.
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Current Clinical Brain Tumor Imaging.
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Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients.
Vesselin Z. Miloushev,Kristin L. Granlund,Rostislav Boltyanskiy,Serge K. Lyashchenko,Lisa M. DeAngelis,Lisa M. DeAngelis,Ingo K. Mellinghoff,Ingo K. Mellinghoff,Cameron Brennan,Cameron Brennan,Viviane Tabar,Viviane Tabar,T. Jonathan Yang,Andrei I. Holodny,Andrei I. Holodny,Ramon E. Sosa,YanWei W. Guo,Albert P. Chen,James Tropp,Fraser Robb,Kayvan R. Keshari +20 more
TL;DR: The results suggest that HP 13C pyruvate-to-lactate conversion may be a viable metabolic biomarker for assessing tumor response, and enables metabolic imaging in the brain and can be a quantitative biomarkers for active tumors.
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