Management of glioblastoma: State of the art and future directions

Aaron C Tan, David M Ashley, Giselle Y López, Michael Malinzak, Henry S Friedman, Mustafa Khasraw, Aaron C Tan, David M Ashley, Giselle Y López, Michael Malinzak, Henry S Friedman, Mustafa Khasraw

Abstract

Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be given concurrently with adjuvant temozolomide. At recurrence, there is no standard of care; however, surgery, radiotherapy, and systemic therapy with chemotherapy or bevacizumab are all potential options, depending on the patient's circumstances. Supportive and palliative care remain important considerations throughout the disease course in the multimodality approach to management. The recently revised classification of glioblastoma based on molecular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the underlying pathogenesis of disease. There is a clear need for better therapeutic options, and there have been substantial efforts exploring immunotherapy and precision oncology approaches. In contrast to other solid tumors, however, biological factors, such as the blood-brain barrier and the unique tumor and immune microenvironment, represent significant challenges in the development of novel therapies. Innovative clinical trial designs with biomarker-enrichment strategies are needed to ultimately improve the outcome of patients with glioblastoma.

Keywords: chemotherapy; glioblastoma; immunotherapy; radiotherapy; surgery; targeted therapy.

© 2020 American Cancer Society.

References

    1. Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011-2015. Neuro Oncol. 2018;20(suppl 4):iv1-iv86.
    1. Taphoorn MJ, Sizoo EM, Bottomley A. Review on quality of life issues in patients with primary brain tumors. Oncologist. 2010;15:618-626.
    1. Ostrom QT, Cote DJ, Ascha M, Kruchko C, Barnholtz-Sloan JS. Adult glioma incidence and survival by race or ethnicity in the United States from 2000 to 2014. JAMA Oncol. 2018;4:1254-1262.
    1. Leece R, Xu J, Ostrom QT, Chen Y, Kruchko C, Barnholtz-Sloan JS. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007. Neuro Oncol. 2017;19:1553-1564.
    1. Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL. Epidemiology of brain tumors. Neurol Clin. 2007;25:867-890, vii.
    1. Linos E, Raine T, Alonso A, Michaud D. Atopy and risk of brain tumors: a meta-analysis. J Natl Cancer Inst. 2007;99:1544-1550.
    1. Amirian ES, Zhou R, Wrensch MR, et al. Approaching a scientific consensus on the association between allergies and glioma risk: a report from the Glioma International Case-Control Study. Cancer Epidemiol Biomarkers Prev. 2016;25:282-290.
    1. Scheurer ME, Etzel CJ, Liu M, et al. Familial aggregation of glioma: a pooled analysis. Am J Epidemiol. 2010;172:1099-1107.
    1. Vienne-Jumeau A, Tafani C, Ricard D. Environmental risk factors of primary brain tumors: a review. Rev Neurol (Paris). 2019;175:664-678.
    1. Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95:190-198.
    1. Lamborn KR, Chang SM, Prados MD. Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. Neuro Oncol. 2004;6:227-235.
    1. Keime-Guibert F, Chinot O, Taillandier L, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007;356:1527-1535.
    1. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997-1003.
    1. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372:2499-2508.
    1. Johnson DR, O’Neill BP. Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol. 2012;107:359-364.
    1. Koshy M, Villano JL, Dolecek TA, et al. Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neurooncol. 2012;107:207-212.
    1. Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15(suppl 2):ii1-ii56.
    1. Canoll P, Goldman JE. The interface between glial progenitors and gliomas. Acta Neuropathol. 2008;116:465-477.
    1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131:803-820.
    1. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013;19:764-772.
    1. Aldape K, Zadeh G, Mansouri S, Reifenberger G, von Deimling A. Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 2015;129:829-848.
    1. Miller CR, Perry A. Glioblastoma. Arch Pathol Lab Med. 2007;131:397-406.
    1. Perry A, Wesseling P. Histologic classification of gliomas. Handb Clin Neurol. 2016;134:71-95.
    1. Kleinschmidt-DeMasters BK, Aisner DL, Birks DK, Foreman NK. Epithelioid GBMs show a high percentage of BRAF V600E mutation. Am J Surg Pathol. 2013;37:685-698.
    1. Weller M, Le Rhun E, Preusser M, Tonn JC, Roth P. How we treat glioblastoma. ESMO Open. 2019;4(suppl 2):e000520.
    1. Simon M, Hosen I, Gousias K, et al. TERT promoter mutations: a novel independent prognostic factor in primary glioblastomas. Neuro Oncol. 2015;17:45-52.
    1. Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98-110.
    1. Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol. 1996;6:217-223; discussion 223-224.
    1. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943-1947.
    1. Zawlik I, Vaccarella S, Kita D, Mittelbronn M, Franceschi S, Ohgaki H. Promoter methylation and polymorphisms of the MGMT gene in glioblastomas: a population-based study. Neuroepidemiology. 2009;32:21-29.
    1. Liu XY, Gerges N, Korshunov A, et al. Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol. 2012;124:615-625.
    1. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372:2481-2498.
    1. Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17:510-522.
    1. Karremann M, Gielen GH, Hoffmann M, et al. Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location. Neuro Oncol. 2018;20:123-131.
    1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987-996.
    1. Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318:2306-2316.
    1. Gramatzki D, Roth P, Rushing EJ, et al. Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. Ann Oncol. 2018;29:1431-1436.
    1. Nava F, Tramacere I, Fittipaldo A, et al. Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997-2010. Neuro Oncol. 2014;16:719-727.
    1. Nabors LB, Horbinski C, Robins I. Index table of contents discussion. In: National Comprehensive Cancer Network, ed. NCCN Guidelines in Oncology (NCCN Guidelines®). National Comprehensive Cancer Network; 2019:163.
    1. Noorbakhsh A, Tang JA, Marcus LP, et al. Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis. J Neurosurg. 2014;120:31-39.
    1. Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, et al. Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol. 2014;16:113-122.
    1. Brown TJ, Brennan MC, Li M, et al. Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol. 2016;2:1460-1469.
    1. Molinaro AM, Hervey-Jumper S, Morshed RA, et al. Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol. 2020;6:495-503.
    1. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7:392-401.
    1. Eigenbrod S, Trabold R, Brucker D, et al. Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients. Acta Neurochir (Wien). 2014;156:1427-1440.
    1. Brindle KM, Izquierdo-Garcia JL, Lewis DY, Mair RJ, Wright AJ. Brain tumor imaging. J Clin Oncol. 2017;35:2432-2438.
    1. Berntsen EM, Gulati S, Solheim O, et al. Functional magnetic resonance imaging and diffusion tensor tractography incorporated into an intraoperative 3-dimensional ultrasound-based neuronavigation system: impact on therapeutic strategies, extent of resection, and clinical outcome. Neurosurgery. 2010;67:251-264.
    1. Abhinav K, Yeh FC, Mansouri A, Zadeh G, Fernandez-Miranda JC. High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery. Neuro Oncol. 2015;17:1199-1209.
    1. Hervey-Jumper SL, Berger MS. Maximizing safe resection of low- and high-grade glioma. J Neurooncol. 2016;130:269-282.
    1. Stummer W, Tonn JC, Mehdorn HM, et al. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article. J Neurosurg. 2011;114:613-623.
    1. Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol. 2011;12:997-1003.
    1. Ringel F, Pape H, Sabel M, et al. Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. Neuro Oncol. 2016;18:96-104.
    1. Suchorska B, Weller M, Tabatabai G, et al. Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. Neuro Oncol. 2016;18:549-556.
    1. Chowdhary SA, Ryken T, Newton HB. Survival outcomes and safety of carmustine wafers in the treatment of high-grade gliomas: a meta-analysis. J Neurooncol. 2015;122:367-382.
    1. Dixit S, Hingorani M, Achawal S, Scott I. The sequential use of carmustine wafers (Gliadel®) and post-operative radiotherapy with concomitant temozolomide followed by adjuvant temozolomide: a clinical review. Br J Neurosurg. 2011;25:459-469.
    1. Pallud J, Audureau E, Noel G, et al. Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort. Neuro Oncol. 2015;17:1609-1619.
    1. Burri SH, Prabhu RS, Sumrall AL, et al. BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative period after tumor resection followed by radiation therapy with TMZ in patients with newly diagnosed high grade glioma: final results of a prospective, multi-institutional, phase II trial. J Neurooncol. 2015;123:259-266.
    1. Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-Brain Tumor Treatment Group. Lancet. 1995;345:1008-1012.
    1. Lawrence YR, Li XA, el Naqa I, et al. Radiation dose-volume effects in the brain. Int J Radiat Oncol Biol Phys. 2010;76(3 suppl):S20-S27.
    1. Cabrera AR, Kirkpatrick JP, Fiveash JB, et al. Radiation therapy for glioblastoma: executive summary of an American Society for Radiation Oncology evidence-based clinical practice guideline. Pract Radiat Oncol. 2016;6:217-225.
    1. Roa W, Brasher PMA, Bauman G, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004;22:1583-1588.
    1. Perry JR, Laperriere N, O’Callaghan CJ, et al. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017;376:1027-1037.
    1. Malmstrom A, Gronberg BH, Marosi C, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012;13:916-926.
    1. Wick A, Kessler T, Elia AEH, et al. Glioblastoma in elderly patients: solid conclusions built on shifting sand? Neuro Oncol. 2018;20:174-183.
    1. Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47:291-298.
    1. Fogh SE, Andrews DW, Glass J, et al. Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas. J Clin Oncol. 2010;28:3048-3053.
    1. Gutin PH, Iwamoto FM, Beal K, et al. Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 2009;75:156-163.
    1. Cabrera AR, Cuneo KC, Desjardins A, et al. Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial. Int J Radiat Oncol Biol Phys. 2013;86:873-879.
    1. Wick W, Platten M, Meisner C, et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012;13:707-715.
    1. Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013;31:4085-4091.
    1. Balana C, Mesia Barroso C, Berron SDB, et al. Randomized phase IIb clinical trial of continuation or non-continuation with six cycles of temozolomide after the first six cycles of standard first-line treatment in patients with glioblastoma: a Spanish Research Group in Neuro-Oncology (GEINO) trial [abstract]. J Clin Oncol. 2019;37(15 suppl):2001.
    1. Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709-722.
    1. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370:699-708.
    1. Weller M, Tabatabai G, Kastner B, et al. MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR Trial. Clin Cancer Res. 2015;21:2057-2064.
    1. Wick W, Puduvalli VK, Chamberlain MC, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010;28:1168-1174.
    1. Jungk C, Chatziaslanidou D, Ahmadi R, et al. Chemotherapy with BCNU in recurrent glioma: analysis of clinical outcome and side effects in chemotherapy-naïve patients. BMC Cancer. 2016;16:81.
    1. Carvalho BF, Fernandes AC, Almeida DS, et al. Second-line chemotherapy in recurrent glioblastoma: a 2-cohort study. Oncol Res Treat. 2015;38:348-354.
    1. Schmidt F, Fischer J, Herrlinger U, Dietz K, Dichgans J, Weller M. PCV chemotherapy for recurrent glioblastoma. Neurology. 2006;66:587-589.
    1. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733-4740.
    1. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740-745.
    1. Wick W, Gorlia T, Bendszus M, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017;377:1954-1963.
    1. Badruddoja MA, Pazzi M, Sanan A, et al. Phase II study of bi-weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma. Cancer Chemother Pharmacol. 2017;80:715-721.
    1. Desjardins A, Reardon DA, Coan A, et al. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 2012;118:1302-1312.
    1. Ameratunga M, Pavlakis N, Wheeler H, Grant R, Simes J, Khasraw M. Anti-angiogenic therapy for high-grade glioma. Cochrane Database Syst Rev. 2018;11:CD008218.
    1. Stupp R, Wong ET, Kanner AA, et al. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012;48:2192-2202.
    1. Hottinger AF, Pacheco P, Stupp R. Tumor treating fields: a novel treatment modality and its use in brain tumors. Neuro Oncol. 2016;18:1338-1349.
    1. Cloughesy TF, Lassman AB. NovoTTF: where to go from here? Neuro Oncol. 2017;19:605-608.
    1. Taphoorn MJ, Dirven L, Kanner AA, et al. Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: a secondary analysis of a randomized clinical trial. JAMA Oncol. 2018;4:495-504.
    1. Bradley S, Sherwood PR, Donovan HS, et al. I could lose everything: understanding the cost of a brain tumor. J Neurooncol. 2007;85:329-338.
    1. Sizoo EM, Braam L, Postma TJ, et al. Symptoms and problems in the end-of-life phase of high-grade glioma patients. Neuro Oncol. 2010;12:1162-1166.
    1. van Breemen MS, Rijsman RM, Taphoorn MJ, Walchenbach R, Zwinkels H, Vecht CJ. Efficacy of anti-epileptic drugs in patients with gliomas and seizures. J Neurol. 2009;256:1519-1526.
    1. Benit CP, Vecht CJ. Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids. Neurooncol Pract. 2016;3:245-260.
    1. Usery JB, Michael LM, Sills AK, Finch CK. A prospective evaluation and literature review of levetiracetam use in patients with brain tumors and seizures. J Neurooncol. 2010;99:251-260.
    1. Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;54:1886-1893.
    1. Schiff D, Lee EQ, Nayak L, Norden AD, Reardon DA, Wen PY. Medical management of brain tumors and the sequelae of treatment. Neuro Oncol. 2015;17:488-504.
    1. Pitter KL, Tamagno I, Alikhanyan K, et al. Corticosteroids compromise survival in glioblastoma. Brain. 2016;139(pt 5):1458-1471.
    1. Perry JR. Thromboembolic disease in patients with high-grade glioma. Neuro Oncol. 2012;14(suppl 4):iv73-iv80.
    1. Krenzlin H, Lorenz V, Alessandri B. The involvement of thrombin in the pathogenesis of glioblastoma. J Neurosci Res. 2017;95:2080-2085.
    1. Lyman GH, Bohlke K, Falanga A; American Society of Clinical Oncology. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Oncol Pract. 2015;11:e442-e444.
    1. Robins HI, O’Neill A, Gilbert M, et al. Effect of dalteparin and radiation on survival and thromboembolic events in glioblastoma multiforme: a phase II ECOG trial. Cancer Chemother Pharmacol. 2008;62:227-233.
    1. Perry JR, Julian JA, Laperriere NJ, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost. 2010;8:1959-1965.
    1. Pace A, Dirven L, Koekkoek JAF, et al. European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma. Lancet Oncol. 2017;18:e330-e340.
    1. Stupp R, Dietrich PY, Ostermann Kraljevic S, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol. 2002;20:1375-1382.
    1. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459-466.
    1. Ransohoff RM, Engelhardt B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol. 2012;12:623-635.
    1. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523:337-341.
    1. Nduom EK, Weller M, Heimberger AB. Immunosuppressive mechanisms in glioblastoma. Neuro Oncol. 2015;17(suppl 7):vii9-vii14.
    1. Li B, Severson E, Pignon JC, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol. 2016;17:174.
    1. Han S, Zhang C, Li Q, et al. Tumour-infiltrating CD4(+) and CD8(+) lymphocytes as predictors of clinical outcome in glioma. Br J Cancer. 2014;110:2560-2568.
    1. Heimberger AB, Abou-Ghazal M, Reina-Ortiz C, et al. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin Cancer Res. 2008;14:5166-5172.
    1. Wainwright DA, Chang AL, Dey M, et al. Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors. Clin Cancer Res. 2014;20:5290-5301.
    1. Heimberger AB, Sun W, Hussain SF, et al. Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study. Neuro Oncol. 2008;10:98-103.
    1. Lim M, Xia Y, Bettegowda C, Weller M. Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol. 2018;15:422-442.
    1. Weller M, Kaulich K, Hentschel B, et al. Assessment and prognostic significance of the epidermal growth factor receptor vIII mutation in glioblastoma patients treated with concurrent and adjuvant temozolomide radiochemotherapy. Int J Cancer. 2014;134:2437-2447.
    1. 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;18:1373-1385.
    1. Reardon DA, Desjardins A, Vredenburgh JJ, et al. Rindopepimut with bevacizumab for patients with relapsed EGFRvIII-expressing glioblastoma (ReACT): results of a double-blind randomized phase II trial. Clin Cancer Res. 2020;26:1586-1594.
    1. Liau LM, Ashkan K, Tran DD, et al. First results on survival from a large phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018;16:142. Erratum in: J Transl Med. 2018;16:179.
    1. Lichty BD, Breitbach CJ, Stojdl DF, Bell JC. Going viral with cancer immunotherapy. Nat Rev Cancer. 2014;14:559-567.
    1. Desjardins A, Gromeier M, Herndon JE, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med. 2018;379:150-161.
    1. Gromeier M, Alexander L, Wimmer E. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc Natl Acad Sci U S A. 1996;93:2370-2375.
    1. Chandramohan V, Bryant JD, Piao H, et al. Validation of an immunohistochemistry assay for detection of CD155, the poliovirus receptor, in malignant gliomas. Arch Pathol Lab Med. 2017;141:1697-1704.
    1. Reardon DA, Omuro A, Brandes AA, et al. OS10.3 Randomized phase 3 study evaluating the efficacy and safety of nivolumab vs bevacizumab in patients with recurrent glioblastoma: CheckMate 143 [abstract]. Neuro Oncol. 2017;19(suppl 3):iii21.
    1. Lukas RV, Rodon J, Becker K, et al. Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma. J Neurooncol. 2018;140:317-328.
    1. Brown CE, Alizadeh D, Starr R, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. 2016;375:2561-2569.
    1. O’Rourke DM, Nasrallah MP, Desai A, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9:eaaa0984.
    1. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061-1068.
    1. Barthel FP, Johnson KC, Varn FS, et al. Longitudinal molecular trajectories of diffuse glioma in adults. Nature. 2019;576:112-120.
    1. Yung WK, Vredenburgh JJ, Cloughesy TF, et al. Safety and efficacy of erlotinib in first-relapse glioblastoma: a phase II open-label study. Neuro Oncol. 2010;12:1061-1070.
    1. Raizer JJ, Abrey LE, Lassman AB, et al. A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy. Neuro Oncol. 2010;12:95-103.
    1. Prados MD, Chang SM, Butowski N, et al. Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol. 2009;27:579-584.
    1. van den Bent M, Eoli M, Sepulveda JM, et al. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma. Neuro Oncol. Published online November 20, 2019. doi:10.1093/neuron/noz222
    1. Lassman A, Pugh S, Wang T, et al. ACTR-21. A randomized, double-blind, placebo-controlled phase 3 trial of depatuxizumab mafodotin (ABT-414) in epidermal growth factor receptor (EGFR) amplified (AMP) newly diagnosed glioblastoma (nGBM) [abstract]. Neuro Oncol. 2019;21(suppl 6):vi17.
    1. Wen PY, Touat M, Alexander BM, et al. Buparlisib in patients with recurrent glioblastoma harboring phosphatidylinositol 3-kinase pathway activation: an open-label, multicenter, multi-arm, phase II trial. J Clin Oncol. 2019;37:741-750.
    1. Ma DJ, Galanis E, Anderson SK, et al. A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K. Neuro Oncol. 2015;17:1261-1269.
    1. Wick W, Gorlia T, Bady P, et al. Phase II study of radiotherapy and temsirolimus versus radiochemotherapy with temozolomide in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation (EORTC 26082). Clin Cancer Res. 2016;22:4797-4806.
    1. Batchelor TT, Mulholland P, Neyns B, et al. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013;31:3212-3218.
    1. Lombardi G, De Salvo GL, Brandes AA, et al. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019;20:110-119.
    1. Kalpathy-Cramer J, Chandra V, Da X, et al. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. J Neurooncol. 2017;131:603-610.
    1. Iwamoto FM, Lamborn KR, Robins HI, et al. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro Oncol. 2010;12:855-861.
    1. Hutterer M, Nowosielski M, Haybaeck J, et al. A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07). Neuro Oncol. 2014;16:92-102.
    1. Dahiya S, Emnett RJ, Haydon DH, et al. BRAF-V600E mutation in pediatric and adult glioblastoma. Neuro Oncol. 2014;16:318-319.
    1. Kaley T, Touat M, Subbiah V, et al. BRAF inhibition in BRAFV600-mutant gliomas: results from the VE-BASKET study. J Clin Oncol. 2018;36:3477-3484.
    1. Wen P, Alexander S, Yung-Jue B, et al. Rare-09. Efficacy and safety of dabrafenib + trametinib in patients with recurrent/refractory BRAF V600E-mutated high-grade glioma (HGG) [abstract]. Neuro Oncol. 2018;20(suppl 6):vi238.
    1. Shah N, Lankerovich M, Lee H, Yoon JG, Schroeder B, Foltz G. Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data. BMC Genomics. 2013;14:818.
    1. Ferguson SD, Zhou S, Huse JT, et al. Targetable gene fusions associate with the IDH wild-type astrocytic lineage in adult gliomas. J Neuropathol Exp Neurol. 2018;77:437-442.
    1. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846.
    1. Singh D, Chan JM, Zoppoli P, et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 2012;337:1231-1235.
    1. Demetri GD, Paz-Ares L, Farago AF, et al. LBA4 efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001 [abstract]. Ann Oncol. 2018;29(suppl 9):mdy483-003.
    1. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378:731-739.
    1. Rangaraju S, Farago A, Heym KM, et al. P14.19 Preclinical and clinical efficacy of entrectinib in primary and metastatic brain tumors harboring NTRK, ROS1, or ALK gene fusions [abstract]. Neuro Oncol. 2017;19(suppl 3):iii106.
    1. Drilon AE, DuBois SG, Farago AF, et al. Activity of larotrectinib in TRK fusion cancer patients with brain metastases or primary central nervous system tumors [abstract]. J Clin Oncol. 2019;37(15 suppl):2006.
    1. Di Stefano AL, Fucci A, Frattini V, et al. Detection, characterization, and inhibition of FGFR-TACC fusions in IDH wild-type glioma. Clin Cancer Res. 2015;21:3307-3317.

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