High-grade glioma therapy: adding flexibility in trial design to improve patient outcomes

References

• Burnett T, Mozgunov P, Pallmann P, et al. Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs. BMC Med. 2020 Nov 19;18(1):352.
   PubMed Web of Science ®Google Scholar
• Alexander BM, Wen PY, Trippa L, et al. Biomarker-based adaptive trials for patients with glioblastoma–lessons from I-SPY 2. Neuro Oncol. 2013;15(8):972–978.
   PubMed Web of Science ®Google Scholar
• Di Nunno V, Franceschi E, Tosoni A, et al. Glioblastoma: emerging treatments and novel trial designs. Cancers (Basel). 2021 Jul 26;13(15):3750.
   PubMed Web of Science ®Google Scholar
• Alexander BM, Ba S, Berger MS, et al. Adaptive global innovative learning environment for glioblastoma: GBM AGILE. Clin Cancer Res. 2018 Feb 15;24(4):737–743.
   PubMed Web of Science ®Google Scholar
• Alexander BM, Trippa L, Gaffey S, et al. Individualized screening trial of innovative glioblastoma therapy (INSIGHT): a bayesian adaptive platform trial to develop precision medicines for patients with glioblastoma. JCO Precis Oncol. 2019;3.
   PubMed Web of Science ®Google Scholar
• Pardridge WM. The blood-brain barrier: bottleneck in brain drug development. NeuroRx. 2005 Jan;2(1):3–14.
   PubMedGoogle Scholar
• Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020 Nov 18; 17(1):69.
   PubMed Web of Science ®Google Scholar
• Ghose AK, Herbertz T, Hudkins RL, et al. Knowledge-Based, Central Nervous System (CNS) lead selection and lead optimization for CNS drug discovery. ACS Chem Neurosci. 2012 Jan 18;3(1):50–68.
   PubMed Web of Science ®Google Scholar
• Grossman SA, Romo CG, Rudek MA, et al. Baseline requirements for novel agents being considered for phase II/III brain cancer efficacy trials: conclusions from the adult brain tumor consortium’s first workshop on CNS drug delivery. Neuro Oncol. 2020 Jun 7;22:1422–1424.
   PubMed Web of Science ®Google Scholar
• Pocock SJ. Clinical trials: a practical approach. Chichester West Sussex; New York:Wiley;1983. A Wiley medical publication.
   Google Scholar
• ICH Guidelines 2020. [accessed 2022 Jan 13]. Available from: https://www.ich.org/page/ich-guidelines ** Reviews the common criteria used for drug development internationally
   Google Scholar
• Piantadosi S. Clinical trials: a methodologic perspective. Third edition. ed. Wiley series in probability and statistics. Hoboken NJ: Wiley; 2017.
   Google Scholar
• Martin JH, Dimmitt S. The rationale of dose-response curves in selecting cancer drug dosing. Br J Clin Pharmacol. 2019 Oct;85(10):2198–2204.
   PubMed Web of Science ®Google Scholar
• Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20; 101(10):708–720.
   PubMedGoogle Scholar
• Reynolds AR. Potential relevance of bell-shaped and u-shaped dose-responses for the therapeutic targeting of angiogenesis in cancer. Dose Response. 2010 Apr 23; 8(3):253–284.
   PubMed Web of Science ®Google Scholar
• Ramaiah L, Hinrichs MJ, Skuba EV, et al. Interpreting and integrating clinical and anatomic pathology results. Toxicol Pathol. 2017 Jan;45(1):223–237.
   PubMed Web of Science ®Google Scholar
• Fraisse J, Dinart D, Tosi D, et al. Optimal biological dose: a systematic review in cancer phase I clinical trials. BMC Cancer. 2021 Jan 13;21(1):60.
   PubMed Web of Science ®Google Scholar
• Kraus VB. Biomarkers as drug development tools: discovery, validation, qualification and use. Nat Rev Rheumatol. 2018 Jun;14(6):354–362.
   PubMed Web of Science ®Google Scholar
• Medikonda R, Dunn G, Rahman M, et al. A review of glioblastoma immunotherapy. J Neurooncol. 2021 Jan;151(1):41–53.
   PubMed Web of Science ®Google Scholar
• Agrawal S, Feng Y, Roy A, et al. Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy. J Immunother Cancer. 2016;4:72.
   PubMed Web of Science ®Google Scholar
• Boyiadzis MM, Kirkwood JM, Marshall JL, et al. Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease. J Immunother Cancer. 2018 May 14;6(1):35.
   PubMedGoogle Scholar
• Smoragiewicz M, Bogaerts J, Calvo E, et al. Design and conduct of early clinical studies of immunotherapy agent combinations: recommendations from the task force on methodology for the development of innovative cancer therapies. Ann Oncol. 2018 Nov 1;29(11):2175–2182.
   PubMed Web of Science ®Google Scholar
• Zeng J, See AP, Phallen J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):343–349.
   PubMed Web of Science ®Google Scholar
• Park JJH, Hsu G, Siden EG, et al. An overview of precision oncology basket and umbrella trials for clinicians. CA Cancer J Clin. 2020 Mar;70(2):125–137.
   PubMed Web of Science ®Google Scholar
• Simon R, Blumenthal GM, Rothenberg ML, et al. The role of nonrandomized trials in the evaluation of oncology drugs. Clin Pharmacol Ther. 2015 May;97(5):502–507.
   PubMed Web of Science ®Google Scholar
• Selaru P, Tang Y, Huang B, et al. Sufficiency of single-arm studies to support registration of targeted agents in molecularly selected patients with cancer: lessons from the clinical development of crizotinib. Clin Transl Sci. 2016 Apr;9(2):63–73.
   PubMed Web of Science ®Google Scholar
• Grayling MJ, Dimairo M, Mander AP, et al. A review of perspectives on the use of randomization in phase II oncology trials. J Natl Cancer Inst. 2019 Dec 1;111(12):1255–1262.
   PubMedGoogle Scholar
• FDA. Adaptive Design Clinical Trials for Drugs and Biologics Guidance for Industry [Internet]. US Department of Health and Human Services. November 2019 [accessed 2022 Jan 13]: https://www.fda.gov/media/78495/download
   Google Scholar
• Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231–1251.
   PubMed Web of Science ®Google Scholar
• Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014 Jun 20;344(6190):1396–1401.
   PubMed Web of Science ®Google Scholar
• Hu C, Dignam JJ. Biomarker-Driven oncology clinical trials: key design elements, types, features, and practical considerations. JCO Precis Oncol. 2019;3. ** Practical considerations for biomarker-driven oncology trial design.
   Google Scholar
• Freidlin B, Korn EL. Biomarker enrichment strategies: matching trial design to biomarker credentials. Nat Rev Clin Oncol. 2014 Feb;11(2):81–90.
   PubMed Web of Science ®Google Scholar
• Dancey JE, Dobbin KK, Groshen S, et al. Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents. Clin Cancer Res. 2010 Mar 15;16(6):1745–1755.
   PubMed Web of Science ®Google Scholar
• (NCI/CCCT) NCI. Biomarker, Imaging, and Quality of Life Studies Funding Program (BIQSFP) [Internet]. 2021 [accessed 2022 Jan 13]:https://www.cancer.gov/about-nci/organization/ccct/funding/biqsfp/fy21-biqsfp-guidelines.pdf.
   Google Scholar
• Blakeley JO, Olson J, Grossman SA, et al. Effect of blood brain barrier permeability in recurrent high grade gliomas on the intratumoral pharmacokinetics of methotrexate: a microdialysis study. J Neurooncol. 2009 Jan;91(1):51–58.
   PubMed Web of Science ®Google Scholar
• Wen PY, Chang SM, Lamborn KR, et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: north American Brain Tumor Consortium trial 04-02. Neuro Oncol. 2014 Apr;16(4):567–578.
   PubMed Web of Science ®Google Scholar
• Omuro A, Beal K, McNeill K, et al. Multicenter phase IB trial of carboxyamidotriazole orotate and temozolomide for recurrent and newly diagnosed glioblastoma and other anaplastic gliomas. J Clin Oncol. 2018 Jun 10;36(17):1702–1709.
   PubMed Web of Science ®Google Scholar
• Hegi ME, Diserens AC, Bady P, et al. Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib–a phase II trial. Mol Cancer Ther. 2011 Jun;10(6):1102–1112.
   PubMed Web of Science ®Google Scholar
• Sanai N, Li J, Boerner J, et al. Phase 0 trial of AZD1775 in first-recurrence glioblastoma patients. Clin Cancer Res. 2018 Aug 15;24(16):3820–3828.
   PubMed Web of Science ®Google Scholar
• Kaley T, Touat M, Subbiah V, et al. BRAF inhibition in BRAF V600 -Mutant gliomas: results from the ve-basket study. J Clin Oncol. 2018 Dec 10;36(35):3477–3484.
   PubMed Web of Science ®Google Scholar
• Alexander BM, Galanis E, Yung WK, et al. Brain malignancy steering committee clinical trials planning workshop: report from the targeted therapies working group. Neuro Oncol. 2015 Feb;17(2):180–188.
   PubMed Web of Science ®Google Scholar
• Cihoric N, Tsikkinis A, Minniti G, et al. Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov. Radiat Oncol. 2017 Jan 3;12(1):1.
   PubMedGoogle Scholar
• Le Rhun E, Preusser M, Roth P, et al. Molecular targeted therapy of glioblastoma. Cancer Treat Rev. 2019 Nov;80:101896.
   PubMed Web of Science ®Google Scholar
• Grossman SA, Schreck KC, Ballman K, et al. Point/counterpoint: randomized versus single-arm phase II clinical trials for patients with newly diagnosed glioblastoma. Neuro Oncol. 2017 Apr 1;19(4):469–474.
   PubMed Web of Science ®Google Scholar
• Grossman SA, Ye X, Piantadosi S, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 2010 Apr 15;16(8):2443–2449.
   PubMed Web of Science ®Google Scholar
• Monzon JG, Hay AE, McDonald GT, et al. Correlation of single arm versus randomised phase 2 oncology trial characteristics with phase 3 outcome. Eur J Cancer. 2015 Nov;51(17):2501–2507.
   PubMed Web of Science ®Google Scholar
• FDA. Guidance for industry choice of control group and related issues in clinical trials. US Department of Health and Human Services. May 2001:https://www.fda.gov/media/71349/download.
   Google Scholar
• Tanguturi SK, Trippa L, Ramkissoon SH, et al. Leveraging molecular datasets for biomarker-based clinical trial design in glioblastoma. Neuro Oncol. 2017 Jul 1;19(7):908–917.
   PubMed Web of Science ®Google Scholar
• FDA. Real-World Evidence [ website]. [ updated 1/7/2022; cited 2021]. https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence].
   Google Scholar
• FDA. Considerations for the use of real-world data and real-world evidence to support regulatory decision-making for drug and biological products 2021 [ updated 12/2021; cited 2022]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-real-world-data-and-real-world-evidence-support-regulatory-decision-making-drug
   Google Scholar
• FDA. Draft guidance: data standards for drug and biological product submissions containing real-world data 2021 [ updated 10/2021; cited 2021]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-standards-drug-and-biological-product-submissions-containing-real-world-data
   Google Scholar
• Lee EQ, Weller M, Sul J, et al. Optimizing eligibility criteria and clinical trial conduct to enhance clinical trial participation for primary brain tumor patients. Neuro Oncol. 2020 May 15;22(5):601–612.
   PubMed Web of Science ®Google Scholar
• Lenting K, Verhaak R, Ter Laan M, et al. Glioma: experimental models and reality. Acta Neuropathol. 2017 Feb;133(2):263–282.
   PubMed Web of Science ®Google Scholar
• Benjamin RK, Hochberg FH, Fox E, et al. Review of microdialysis in brain tumors, from concept to application: first annual Carolyn Frye-Halloran symposium. Neuro Oncol. 2004 Jan;6(1):65–74.
   PubMed Web of Science ®Google Scholar
• Blakeley J, Portnow J. Microdialysis for assessing intratumoral drug disposition in brain cancers: a tool for rational drug development. Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1477–1491.
   PubMed Web of Science ®Google Scholar
• Jackson S, Weingart J, Nduom EK, et al. The effect of an adenosine A2A agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma. Fluids Barriers CNS. 2018 Jan 15;15(1):2.
   PubMedGoogle Scholar
• Portnow J, Badie B, Chen M, et al. The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: potential implications for the current approach to chemoradiation. Clin Cancer Res. 2009 Nov 15;15(22):7092–7098.
   PubMed Web of Science ®Google Scholar
• Parchment RE, Doroshow JH. Pharmacodynamic endpoints as clinical trial objectives to answer important questions in oncology drug development. Semin Oncol. 2016 Aug;43(4):514–525.
   PubMed Web of Science ®Google Scholar
• Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. Neurosurgery. 2019 Dec 1; 85(6):E967–E974.
   PubMed Web of Science ®Google Scholar
• Vogelbaum MA, Krivosheya D, Borghei-Razavi H, et al. Phase 0 and window of opportunity clinical trial design in neuro-oncology: a RANO review. Neuro Oncol. 2020 Nov 26;22(11):1568–1579.
   PubMed Web of Science ®Google Scholar
• Bundgaard M, Abbott NJ. All vertebrates started out with a glial blood-brain barrier 4-500 million years ago. Glia. 2008 May;56(7):699–708.
   PubMed Web of Science ®Google Scholar
• Hindle SJ, Bainton RJ. Barrier mechanisms in the drosophila blood-brain barrier. Front Neurosci. 2014;8:414.
   PubMed Web of Science ®Google Scholar
• van Tellingen O, Yetkin-Arik B, de Gooijer MC, et al. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat. 2015 Mar;19:1–12.
   PubMed Web of Science ®Google Scholar
• Cash A, Theus MH. Mechanisms of blood-brain barrier dysfunction in traumatic brain injury. Int J Mol Sci. 2020 May 8; 21(9):3344.
   Web of Science ®Google Scholar
• Trnovec T, Kallay Z, Bezek S. Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances. Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1581–1587.
   PubMed Web of Science ®Google Scholar
• Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2020 Jan;20(1):26–41.
   PubMed Web of Science ®Google Scholar
• Varatharaj A, Galea I. The blood-brain barrier in systemic inflammation. Brain Behav Immun. 2017 Feb;60:1–12.
   PubMed Web of Science ®Google Scholar
• Kroll RA, Neuwelt EA. Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. discussion 1099-100. Neurosurgery. 1998 May;42(5):1083–1099.
   PubMed Web of Science ®Google Scholar
• Cenciarini M, Valentino M, Belia S, et al. Dexamethasone in glioblastoma multiforme therapy: mechanisms and controversies. Front Mol Neurosci. 2019;12:65.
   PubMed Web of Science ®Google Scholar
• Michinaga S, Koyama Y. Pathogenesis of brain edema and investigation into anti-edema drugs. Int J Mol Sci. 2015 Apr 30; 16(5):9949–9975.
   PubMed Web of Science ®Google Scholar
• Haumann R, Videira JC, Kaspers GJL, et al. Overview of current drug delivery methods across the blood-brain barrier for the treatment of primary brain tumors. CNS Drugs. 2020 Nov;34(11):1121–1131.
   PubMed Web of Science ®Google Scholar
• Drean A, Goldwirt L, Verreault M, et al. Blood-brain barrier, cytotoxic chemotherapies and glioblastoma. Expert Rev Neurother. 2016 Nov;16(11):1285–1300.
   PubMed Web of Science ®Google Scholar
• Mohme M, Schliffke S, Maire CL, et al. Immunophenotyping of newly diagnosed and recurrent glioblastoma defines distinct immune exhaustion profiles in peripheral and tumor-infiltrating lymphocytes. Clin Cancer Res. 2018 Sep 1;24(17):4187–4200.
   PubMed Web of Science ®Google Scholar
• Qazi MA, Vora P, Venugopal C, et al. Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann Oncol. 2017 Jul 1;28(7):1448–1456. https://doi.org/10.1093/annonc/mdx169.
   Google Scholar
• Birzu C, French P, Caccese M, et al. Recurrent glioblastoma: from molecular landscape to new treatment perspectives. Cancers (Basel). 2020 Dec 26;13(1):47.
   Web of Science ®Google Scholar
• Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997–1003.
   PubMed Web of Science ®Google Scholar
• Lee JS, Yost SE, Yuan Y. Neoadjuvant treatment for triple negative breast cancer: recent progresses and challenges. Cancers (Basel). 2020 May 29;12(6):1404.
   Web of Science ®Google Scholar
• Guerrini-Rousseau L, Abbas R, Huybrechts S, et al. Role of neoadjuvant chemotherapy in metastatic medulloblastoma: a comparative study in 92 children. Neuro Oncol. 2020 Nov 26;22(11):1686–1695.
   PubMed Web of Science ®Google Scholar
• Hidalgo ET, Snuderl M, Orillac C, et al. Subgroup-specific outcomes of children with malignant childhood brain tumors treated with an irradiation-sparing protocol. Childs Nerv Syst. 2020 Jan;36(1):133–144.
   PubMed Web of Science ®Google Scholar
• Lopez-Aguilar E, Sepulveda-Vildosola AC, Rivera-Marquez H, et al. Preirradiation ifosfamide, carboplatin, and etoposide for the treatment of anaplastic astrocytomas and glioblastoma multiforme: a phase II study. Arch Med Res. 2000 Mar-Apr;31(2):186–190.
   PubMed Web of Science ®Google Scholar
• Chinot OL, Barrie M, Fuentes S, et al. Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol. 2007 Apr 20;25(12):1470–1475.
   PubMed Web of Science ®Google Scholar
• Cloughesy TF, Mochizuki AY, Orpilla JR, et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019 Mar;25(3):477–486.
   PubMed Web of Science ®Google Scholar
• Weller M, Butowski N, Tran DD, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1373–1385.
   PubMed Web of Science ®Google Scholar
• Penas-Prado M, Hess KR, Fisch MJ, et al. Randomized phase II adjuvant factorial study of dose-dense temozolomide alone and in combination with isotretinoin, celecoxib, and/or thalidomide for glioblastoma. Neuro Oncol. 2015 Feb;17(2):266–273.
   PubMed Web of Science ®Google Scholar
• Taylor JW, Molinaro AM, Butowski N, et al. Clinical trial endpoints for patients with gliomas. Neurooncol Pract. 2017 Dec;4(4):201–208.
   PubMed Web of Science ®Google Scholar
• Han K, Ren M, Wick W, et al. Progression-free survival as a surrogate endpoint for overall survival in glioblastoma: a literature-based meta-analysis from 91 trials. Neuro Oncol. 2014 May;16(5):696–706.
   PubMed Web of Science ®Google Scholar
• Alexander BM, Trippa L. Getting it first versus getting it right: weighing the value of and evidence for progression-free survival as a surrogate endpoint for overall survival in glioblastoma. Neuro Oncol. 2015 May;17(5):765–766.
   PubMed Web of Science ®Google Scholar
• Nayak L, DeAngelis LM, Brandes AA, et al. The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria. Neuro Oncol. 2017 May 1;19(5):625–635.
   PubMed Web of Science ®Google Scholar
• Ellingson BM, Chung C, Pope WB, et al. Pseudoprogression, radionecrosis, inflammation or true tumor progression? Challenges associated with glioblastoma response assessment in an evolving therapeutic landscape. J Neurooncol. 2017 Sep;134(3):495–504.
   PubMed Web of Science ®Google Scholar
• Huang RY, Neagu MR, Reardon DA, et al. Pitfalls in the neuroimaging of glioblastoma in the era of antiangiogenic and immuno/targeted therapy - detecting illusive disease, defining response. Front Neurol. 2015;6:33.
   PubMed Web of Science ®Google Scholar
• Okada H, Weller M, Huang R, et al. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015 Nov;16(15):e534–e542.
   PubMedGoogle Scholar
• Dou W, Lin CE, Ding H, et al. Chemical exchange saturation transfer magnetic resonance imaging and its main and potential applications in pre-clinical and clinical studies. Quant Imaging Med Surg. 2019 Oct;9(10):1747–1766.
   PubMed Web of Science ®Google Scholar
• Ma B, Blakeley JO, Hong X, et al. Applying amide proton transfer-weighted MRI to distinguish pseudoprogression from true progression in malignant gliomas. J Magn Reson Imaging. 2016 Aug;44(2):456–462.
   PubMed Web of Science ®Google Scholar
• Sabedot TS, Malta TM, Snyder J, et al. A serum-based DNA methylation assay provides accurate detection of glioma. Neuro Oncol. 2021 Sep 1;23(9):1494–1508.
   PubMed Web of Science ®Google Scholar
• Mattox AK, Yan H, Bettegowda C. The potential of cerebrospinal fluid-based liquid biopsy approaches in CNS tumors. Neuro Oncol. 2019 Dec 17; 21(12):1509–1518.
   PubMed Web of Science ®Google Scholar
• Muller Bark J, Kulasinghe A, Chua B, et al. Circulating biomarkers in patients with glioblastoma. Br J Cancer. 2020 Feb;122(3):295–305.
   PubMed Web of Science ®Google Scholar
• Meng Y, Pople CB, Suppiah S, et al. MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors. Neuro Oncol. 2021 Oct 1;23(10):1789–1797.
   PubMed Web of Science ®Google Scholar
• Jucaite A, Stenkrona P, Cselenyi Z, et al. Brain exposure of the ATM inhibitor AZD1390 in humans-a positron emission tomography study. Neuro Oncol. 2021 Apr 12;23(4):687–696.
   PubMed Web of Science ®Google Scholar
• Beinat C, Patel CB, Xie Y, et al. Evaluation of glycolytic response to multiple classes of anti-glioblastoma drugs by noninvasive measurement of pyruvate kinase M2 using [18F]DASA-23. Mol Imaging Biol. 2020 Feb;22(1):124–133.
   PubMed Web of Science ®Google Scholar
• Bhandari A, Sharma C, Ibrahim M, et al. The role of 2-hydroxyglutarate magnetic resonance spectroscopy for the determination of isocitrate dehydrogenase status in lower grade gliomas versus glioblastoma: a systematic review and meta-analysis of diagnostic test accuracy. Neuroradiology. 2021 Nov;63(11):1823–1830.
   PubMed Web of Science ®Google Scholar
• Kessler LG, Barnhart HX, Buckler AJ, et al. The emerging science of quantitative imaging biomarkers terminology and definitions for scientific studies and regulatory submissions. Stat Methods Med Res. 2015 Feb;24(1):9–26.
   PubMed Web of Science ®Google Scholar