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Current and future strategies for treatment of glioma

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Abstract

Gliomas are one of the most common types of primary brain tumors and have remained particularly challenging to treat. This review illustrates a multidisciplinary approach to the treatment of glioma and glioblastoma. We will review current advances in surgical approaches, novel imaging techniques, advanced molecular characterization of tumors and translational efforts for treatment. We will focus on current clinical trials as well as the pursuit of personalized or precision therapy. We will also comment on the importance of both quality of life of our patients and their care givers.

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References

  1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol (Berl) 114:97–109. doi:10.1007/s00401-007-0243-4

    Article  Google Scholar 

  2. Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro-Oncol 14(Suppl 5):v1–49. doi:10.1093/neuonc/nos218

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ostrom QT, Gittleman H, Stetson L, Virk SM, Barnholtz-Sloan JS (2015) Epidemiology of gliomas. Cancer Treat Res 163:1–14. doi:10.1007/978-3-319-12048-5_1

    Article  PubMed  Google Scholar 

  4. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  5. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507. doi:10.1056/NEJMra0708126

    Article  CAS  PubMed  Google Scholar 

  6. Butowski NA (2015) Epidemiology and diagnosis of brain tumors. Contin Minneap Minn 21:301–313. doi:10.1212/01.CON.0000464171.50638.fa

    Google Scholar 

  7. Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, Wang SS, Bondy M, Houlston R, Jenkins RB, Wrensch M, Yeager M, Ahlbom A, Albanes D, Andersson U, Freeman LEB, Buring JE, Butler MA, Braganza M, Carreon T, Feychting M, Fleming SJ, Gapstur SM, Gaziano JM, Giles GG, Hallmans G, Henriksson R, Hoffman-Bolton J, Inskip PD, Johansen C, Kitahara CM, Lathrop M, Liu C, Le Marchand L, Linet MS, Lonn S, Peters U, Purdue MP, Rothman N, Ruder AM, Sanson M, Sesso HD, Severi G, Shu X-O, Simon M, Stampfer M, Stevens VL, Visvanathan K, White E, Wolk A, Zeleniuch-Jacquotte A, Zheng W, Decker P, Enciso-Mora V, Fridley B, Gao Y-T, Kosel M, Lachance DH, Lau C, Rice T, Swerdlow A, Wiemels JL, Wiencke JK, Shete S, Xiang Y-B, Xiao Y, Hoover RN, Fraumeni JF, Chatterjee N, Hartge P, Chanock SJ (2012) Genome-wide association study of glioma and meta-analysis. Hum Genet 131:1877–1888. doi:10.1007/s00439-012-1212-0

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sanson M, Hosking FJ, Shete S, Zelenika D, Dobbins SE, Ma Y, Enciso-Mora V, Idbaih A, Delattre J-Y, Hoang-Xuan K, Marie Y, Boisselier B, Carpentier C, Wang X-W, Di Stefano AL, Labussière M, Gousias K, Schramm J, Boland A, Lechner D, Gut I, Armstrong G, Liu Y, Yu R, Lau C, Di Bernardo MC, Robertson LB, Muir K, Hepworth S, Swerdlow A, Schoemaker MJ, Wichmann H-E, Müller M, Schreiber S, Franke A, Moebus S, Eisele L, Försti A, Hemminki K, Lathrop M, Bondy M, Houlston RS, Simon M (2011) Chromosome 7p11.2 (EGFR) variation influences glioma risk. Hum Mol Genet 20:2897–2904. doi:10.1093/hmg/ddr192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre J-Y, Hoang-Xuan K, El Hallani S, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lönn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS (2009) Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 41:899–904. doi:10.1038/ng.407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Stacey SN, Sulem P, Jonasdottir A, Masson G, Gudmundsson J, Gudbjartsson DF, Magnusson OT, Gudjonsson SA, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Nexø BA, Tjønneland A, Overvad K, Rudnai P, Gurzau E, Koppova K, Hemminki K, Corredera C, Fuentelsaz V, Grasa P, Navarrete S, Fuertes F, García-Prats MD, Sanambrosio E, Panadero A, De Juan A, Garcia A, Rivera F, Planelles D, Soriano V, Requena C, Aben KK, van Rossum MM, Cremers RGHM, van Oort IM, van Spronsen D-J, Schalken JA, Peters WHM, Helfand BT, Donovan JL, Hamdy FC, Badescu D, Codreanu O, Jinga M, Csiki IE, Constantinescu V, Badea P, Mates IN, Dinu DE, Constantin A, Mates D, Kristjansdottir S, Agnarsson BA, Jonsson E, Barkardottir RB, Einarsson GV, Sigurdsson F, Moller PH, Stefansson T, Valdimarsson T, Johannsson OT, Sigurdsson H, Jonsson T, Jonasson JG, Tryggvadottir L, Rice T, Hansen HM, Xiao Y, Lachance DH, Neill BP O, Kosel ML, Decker PA, Thorleifsson G, Johannsdottir H, Helgadottir HT, Sigurdsson A, Steinthorsdottir V, Lindblom A, Swedish Low-risk Colorectal Cancer Study Group, Sandler RS, Keku TO, Banasik K, Jørgensen T, Witte DR, Hansen T, Pedersen O, Jinga V, Neal DE, Catalona WJ, Wrensch M, Wiencke J, Jenkins RB, Nagore E, Vogel U, Kiemeney LA, Kumar R, Mayordomo JI, Olafsson JH, Kong A, Thorsteinsdottir U, Rafnar T, Stefansson K (2011) A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. Nat Genet 43:1098–1103. doi:10.1038/ng.926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wrensch M, Jenkins RB, Chang JS, Yeh R-F, Xiao Y, Decker PA, Ballman KV, Berger M, Buckner JC, Chang S, Giannini C, Halder C, Kollmeyer TM, Kosel ML, LaChance DH, McCoy L, O’Neill BP, Patoka J, Pico AR, Prados M, Quesenberry C, Rice T, Rynearson AL, Smirnov I, Tihan T, Wiemels J, Yang P, Wiencke JK (2009) Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet 41:905–908. doi:10.1038/ng.408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Melin B, Jenkins R (2013) Genetics in glioma: lessons learned from genome-wide association studies. Curr Opin Neurol 26:688–692. doi:10.1097/WCO.0000000000000033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198. doi:10.3171/jns.2001.95.2.0190

    Article  CAS  PubMed  Google Scholar 

  14. McGirt MJ, Chaichana KL, Gathinji M, Attenello FJ, Than K, Olivi A, Weingart JD, Brem H, Quiñones-Hinojosa AR (2009) Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J Neurosurg 110:156–162. doi:10.3171/2008.4.17536

    Article  PubMed  Google Scholar 

  15. Sanai N, Polley M-Y, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8. doi:10.3171/2011.2.JNS10998

    Article  PubMed  Google Scholar 

  16. Krings T, Schreckenberger M, Rohde V, Spetzger U, Sabri O, Reinges MHT, Hans FJ, Meyer PT, Möller-Hartmann W, Gilsbach JM, Buell U, Thron A (2002) Functional MRI and 18F FDG-positron emission tomography for presurgical planning: comparison with electrical cortical stimulation. Acta Neurochir (Wien) 144:889–899. doi:10.1007/s00701-002-0992-8, discussion 899

    Article  CAS  Google Scholar 

  17. Roux FE, Boulanouar K, Ranjeva JP, Tremoulet M, Henry P, Manelfe C, Sabatier J, Berry I (1999) Usefulness of motor functional MRI correlated to cortical mapping in Rolandic low-grade astrocytomas. Acta Neurochir (Wien) 141:71–79

    Article  CAS  Google Scholar 

  18. Fujiwara N, Sakatani K, Katayama Y, Murata Y, Hoshino T, Fukaya C, Yamamoto T (2004) Evoked-cerebral blood oxygenation changes in false-negative activations in BOLD contrast functional MRI of patients with brain tumors. NeuroImage 21:1464–1471. doi:10.1016/j.neuroimage.2003.10.042

    Article  PubMed  Google Scholar 

  19. Ulmer JL, Hacein-Bey L, Mathews VP, Mueller WM, DeYoe EA, Prost RW, Meyer GA, Krouwer HG, Schmainda KM (2004) Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments. Neurosurgery 55:569–579, discussion 580–581

    Article  PubMed  Google Scholar 

  20. Ganslandt O, Buchfelder M, Hastreiter P, Grummich P, Fahlbusch R, Nimsky C (2004) Magnetic source imaging supports clinical decision making in glioma patients. Clin Neurol Neurosurg 107:20–26. doi:10.1016/j.clineuro.2004.02.027

    Article  CAS  PubMed  Google Scholar 

  21. Ottenhausen M, Krieg SM, Meyer B, Ringel F (2015) Functional preoperative and intraoperative mapping and monitoring: increasing safety and efficacy in glioma surgery. Neurosurg Focus 38, E3. doi:10.3171/2014.10.FOCUS14611

    Article  PubMed  Google Scholar 

  22. Berman JI, Berger MS, Mukherjee P, Henry RG (2004) Diffusion-tensor imaging-guided tracking of fibers of the pyramidal tract combined with intraoperative cortical stimulation mapping in patients with gliomas. J Neurosurg 101:66–72. doi:10.3171/jns.2004.101.1.0066

    Article  PubMed  Google Scholar 

  23. Wu J-S, Zhou L-F, Tang W-J, Mao Y, Hu J, Song Y-Y, Hong X-N, Du G-H (2007) Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in patients with gliomas involving pyramidal tracts. Neurosurgery 61:935–948. doi:10.1227/01.neu.0000303189.80049.ab, discussion 948–949

    Article  PubMed  Google Scholar 

  24. Barone DG, Lawrie TA, Hart MG (2014) Image guided surgery for the resection of brain tumours. Cochrane Database Syst Rev 1, CD009685. doi:10.1002/14651858.CD009685.pub2

    Google Scholar 

  25. de Boer E, Harlaar NJ, Taruttis A, Nagengast WB, Rosenthal EL, Ntziachristos V, van Dam GM (2015) Optical innovations in surgery. Br J Surg 102:e56–72. doi:10.1002/bjs.9713

    Article  PubMed  Google Scholar 

  26. Leroy H-A, Vermandel M, Lejeune J-P, Mordon S, Reyns N (2015) Fluorescence guided resection and glioblastoma in 2015: a review. Lasers Surg Med 47:441–451. doi:10.1002/lsm.22359

    Article  PubMed  Google Scholar 

  27. Parsons DW, Jones S, Zhang X, Lin JC-H, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu I-M, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA, Hartigan J, Smith DR, Strausberg RL, Marie SKN, Shinjo SMO, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812. doi:10.1126/science.1164382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E, Kunii K, Pedraza A, Schalm S, Silverman L, Miller A, Wang F, Yang H, Chen Y, Kernytsky A, Rosenblum MK, Liu W, Biller SA, Su SM, Brennan CW, Chan TA, Graeber TG, Yen KE, Mellinghoff IK (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340:626–630. doi:10.1126/science.1236062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J, Menn O, Osswald M, Oezen I, Ott M, Keil M, Balß J, Rauschenbach K, Grabowska AK, Vogler I, Diekmann J, Trautwein N, Eichmüller SB, Okun J, Stevanović S, Riemer AB, Sahin U, Friese MA, Beckhove P, von Deimling A, Wick W, Platten M (2014) A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 512:324–327. doi:10.1038/nature13387

    Article  CAS  PubMed  Google Scholar 

  30. Aldape K, Zadeh G, Mansouri S, Reifenberger G, von Deimling A (2015) Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol (Berl) 129:829–848. doi:10.1007/s00401-015-1432-1

    Article  CAS  Google Scholar 

  31. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RGW, Aldape KD, Yung WKA, Salama SR, Cooper LAD, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O’Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, von Deimling A, Zhang H, Crain D, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG, Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A, Hayes DN, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD, Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S, Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J, Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV, Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J, Thiessen N, Triche T, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ, Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA, Arachchi H, Benz C, Bernard B, Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P, Ling S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R, Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D, Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T, Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ, Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K, DiMeco F, Duell R, Elder JB, Fehrenbach A, Finocchiaro G, Friedman W, Fulop J, Gardner J, Hermes B, Herold-Mende C, Jungk C, Kendler A, Lehman NL, Lipp E, Liu O, Mandt R, McGraw M, Mclendon R, McPherson C, Neder L, Nguyen P, Noss A, Nunziata R, Ostrom QT, Palmer C, Perin A, Pollo B, Potapov A, Potapova O, Rathmell WK, Rotin D, Scarpace L, Schilero C, Senecal K, Shimmel K, Shurkhay V, Sifri S, Singh R, Sloan AE, Smolenski K, Staugaitis SM, Steele R, Thorne L, Tirapelli DPC, Unterberg A, Vallurupalli M, Wang Y, Warnick R, Williams F, Wolinsky Y, Bell S, Rosenberg M, Stewart C, Huang F, Grimsby JL, Radenbaugh AJ, Zhang J (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498. doi:10.1056/NEJMoa1402121

    Article  Google Scholar 

  32. Hegi ME, Diserens A-C, Gorlia T, Hamou M-F, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JEC, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003. doi:10.1056/NEJMoa043331

    Article  CAS  PubMed  Google Scholar 

  33. van den Bent MJ, Brandes AA, Taphoorn MJB, Kros JM, Kouwenhoven MCM, Delattre J-Y, Bernsen HJJA, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WNM, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K (2013) Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol Off J Am Soc Clin Oncol 31:344–350. doi:10.1200/JCO.2012.43.2229

    Article  Google Scholar 

  34. Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol Off J Am Soc Clin Oncol 31:337–343. doi:10.1200/JCO.2012.43.2674

    Article  CAS  Google Scholar 

  35. Graves EE, Nelson SJ, Vigneron DB, Chin C, Verhey L, McDermott M, Larson D, Sneed PK, Chang S, Prados MD, Lamborn K, Dillon WP (2000) A preliminary study of the prognostic value of proton magnetic resonance spectroscopic imaging in gamma knife radiosurgery of recurrent malignant gliomas. Neurosurgery 46:319–326, discussion 326–328

    Article  CAS  PubMed  Google Scholar 

  36. Pirzkall A, McKnight TR, Graves EE, Carol MP, Sneed PK, Wara WW, Nelson SJ, Verhey LJ, Larson DA (2001) MR-spectroscopy guided target delineation for high-grade gliomas. Int J Radiat Oncol Biol Phys 50:915–928

    Article  CAS  PubMed  Google Scholar 

  37. Pirzkall A, McGue C, Saraswathy S, Cha S, Liu R, Vandenberg S, Lamborn KR, Berger MS, Chang SM, Nelson SJ (2009) Tumor regrowth between surgery and initiation of adjuvant therapy in patients with newly diagnosed glioblastoma. Neuro-Oncol 11:842–852. doi:10.1215/15228517-2009-005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kalpathy-Cramer J, Gerstner ER, Emblem KE, Andronesi OC, Rosen B (2014) Advanced magnetic resonance imaging of the physical processes in human glioblastoma. Cancer Res 74:4622–4637. doi:10.1158/0008-5472.CAN-14-0383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Boxerman JL, Schmainda KM, Weisskoff RM (2006) Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not. AJNR Am J Neuroradiol 27:859–867

    CAS  PubMed  Google Scholar 

  40. Crawford FW, Khayal IS, McGue C, Saraswathy S, Pirzkall A, Cha S, Lamborn KR, Chang SM, Berger MS, Nelson SJ (2009) Relationship of pre-surgery metabolic and physiological MR imaging parameters to survival for patients with untreated GBM. J Neurooncol 91:337–351. doi:10.1007/s11060-008-9719-x

    Article  PubMed  Google Scholar 

  41. van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, Malmström P-O, Collette L, Piérart M, Mirimanoff R, Karim ABMF, Radiotherapy EORTC, Groups BT, the UK Medical Research Council (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet Lond Engl 366:985–990. doi:10.1016/S0140-6736(05)67070-5

    Article  Google Scholar 

  42. Buckner, JC, Pugh SL, Shaw EG, et al. Phase III study of raditiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low grade glioma: RTOG 9802 with Alliance, ECOG, and SWOG. http://meetinglibrary.asco.org/content/127483-144. Accessed 28 Jan 2015

  43. Ung N, Yang I (2015) Nanotechnology to augment immunotherapy for the treatment of glioblastoma multiforme. J Neurooncol 123:473–481. doi:10.1007/s11060-015-1814-1

    Article  CAS  PubMed  Google Scholar 

  44. Vogelbaum MA, Aghi MK (2015) Convection-enhanced delivery for the treatment of glioblastoma. Neuro-Oncol 17(Suppl 2):ii3–ii8. doi:10.1093/neuonc/nou354

    Article  PubMed  PubMed Central  Google Scholar 

  45. Blasberg RG, Patlak CS, Shapiro WR (1977) Distribution of methotrexate in the cerebrospinal fluid and brain after intraventricular administration. Cancer Treat Rep 61:633–641

    CAS  PubMed  Google Scholar 

  46. Walter KA, Tamargo RJ, Olivi A, Burger PC, Brem H (1995) Intratumoral chemotherapy. Neurosurgery 37:1128–1145

    CAS  PubMed  Google Scholar 

  47. Wait SD, Prabhu RS, Burri SH, Atkins TG, Asher AL (2015) Polymeric drug delivery for the treatment of glioblastoma. Neuro-Oncol 17(Suppl 2):ii9–ii23. doi:10.1093/neuonc/nou360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, Whittle IR, Jääskeläinen J, Ram Z (2003) A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-Oncol 5:79–88. doi:10.1215/S1522-8517-02-00023-6

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Valtonen S, Timonen U, Toivanen P, Kalimo H, Kivipelto L, Heiskanen O, Unsgaard G, Kuurne T (1997) Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study. Neurosurgery 41:44–48, discussion 48–49

    Article  CAS  PubMed  Google Scholar 

  50. Westphal M, Ram Z, Riddle V, Hilt D, Bortey E, Executive Committee of the Gliadel Study Group (2006) Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien) 148:269–275. doi:10.1007/s00701-005-0707-z, discussion 275

    Article  CAS  Google Scholar 

  51. Bruce JN, Fine RL, Canoll P, Yun J, Kennedy BC, Rosenfeld SS, Sands SA, Surapaneni K, Lai R, Yanes CL, Bagiella E, DeLaPaz RL (2011) Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan. Neurosurgery 69:1272–1279. doi:10.1227/NEU.0b013e3182233e24, discussion 1279–1280

    Article  PubMed  PubMed Central  Google Scholar 

  52. Alifieris C, Trafalis DT (2015) Glioblastoma multiforme: pathogenesis and treatment. Pharmacol Ther 152:63–82. doi:10.1016/j.pharmthera.2015.05.005

    Article  CAS  PubMed  Google Scholar 

  53. Batchelor TT, Reardon DA, de Groot JF, Wick W, Weller M (2014) Antiangiogenic therapy for glioblastoma: current status and future prospects. Clin Cancer Res 20:5612–5619. doi:10.1158/1078-0432.CCR-14-0834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Winkler F, Kozin SV, Tong RT, Chae S-S, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563. doi:10.1016/j.ccr.2004.10.011

    CAS  PubMed  Google Scholar 

  55. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WKA, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol Off J Am Soc Clin Oncol 27:4733–4740. doi:10.1200/JCO.2008.19.8721

    Article  CAS  Google Scholar 

  56. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol Off J Am Soc Clin Oncol 27:740–745. doi:10.1200/JCO.2008.16.3055

    Article  CAS  Google Scholar 

  57. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722. doi:10.1056/NEJMoa1308345

    Article  CAS  PubMed  Google Scholar 

  58. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699–708. doi:10.1056/NEJMoa1308573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sami A, Karsy M (2013) Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: novel therapeutic agents and advances in understanding. Tumour Biol J Int Soc Oncodev Biol Med 34:1991–2002. doi:10.1007/s13277-013-0800-5

    Article  CAS  Google Scholar 

  60. Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Berkowitz N, Anak O, Niolat J, Jozwiak S (2014) Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. Lancet Oncol 15:1513–1520. doi:10.1016/S1470-2045(14)70489-9

    Article  CAS  PubMed  Google Scholar 

  61. Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Whittemore VH, Thiele EA, Ford JP, Shah G, Cauwel H, Lebwohl D, Sahmoud T, Jozwiak S (2013) Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet Lond Engl 381:125–132. doi:10.1016/S0140-6736(12)61134-9

    Article  CAS  Google Scholar 

  62. Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, McLean CY, Fouse SD, Yamamoto S, Ueda H, Tatsuno K, Asthana S, Jalbert LE, Nelson SJ, Bollen AW, Gustafson WC, Charron E, Weiss WA, Smirnov IV, Song JS, Olshen AB, Cha S, Zhao Y, Moore RA, Mungall AJ, Jones SJM, Hirst M, Marra MA, Saito N, Aburatani H, Mukasa A, Berger MS, Chang SM, Taylor BS, Costello JF (2014) Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 343:189–193. doi:10.1126/science.1239947

    Article  CAS  PubMed  Google Scholar 

  63. Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CLL, Rich JN (2015) Cancer stem cells in glioblastoma. Genes Dev 29:1203–1217. doi:10.1101/gad.261982.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG (2005) Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro-Oncol 7:134–153. doi:10.1215/S1152851704001115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. doi:10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  66. Plautz GE, Barnett GH, Miller DW, Cohen BH, Prayson RA, Krauss JC, Luciano M, Kangisser DB, Shu S (1998) Systemic T cell adoptive immunotherapy of malignant gliomas. J Neurosurg 89:42–51. doi:10.3171/jns.1998.89.1.0042

    Article  CAS  PubMed  Google Scholar 

  67. Plautz GE, Miller DW, Barnett GH, Stevens GH, Maffett S, Kim J, Cohen PA, Shu S (2000) T cell adoptive immunotherapy of newly diagnosed gliomas. Clin Cancer Res Off J Am Assoc Cancer Res 6:2209–2218

    CAS  Google Scholar 

  68. Tsuboi K, Saijo K, Ishikawa E, Tsurushima H, Takano S, Morishita Y, Ohno T (2003) Effects of local injection of ex vivo expanded autologous tumor-specific T lymphocytes in cases with recurrent malignant gliomas. Clin Cancer Res Off J Am Assoc Cancer Res 9:3294–3302

    Google Scholar 

  69. Reardon DA, Freeman G, Wu C, Chiocca EA, Wucherpfennig KW, Wen PY, Fritsch EF, Curry WT, Sampson JH, Dranoff G (2014) Immunotherapy advances for glioblastoma. Neuro-Oncol 16:1441–1458. doi:10.1093/neuonc/nou212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Brown CE, Starr R, Aguilar B, Shami AF, Martinez C, D’Apuzzo M, Barish ME, Forman SJ, Jensen MC (2012) Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells. Clin Cancer Res Off J Am Assoc Cancer Res 18:2199–2209. doi:10.1158/1078-0432.CCR-11-1669

    Article  CAS  Google Scholar 

  71. Chow KKH, Naik S, Kakarla S, Brawley VS, Shaffer DR, Yi Z, Rainusso N, Wu M-F, Liu H, Kew Y, Grossman RG, Powell S, Lee D, Ahmed N, Gottschalk S (2013) T cells redirected to EphA2 for the immunotherapy of glioblastoma. Mol Ther J Am Soc Gene Ther 21:629–637. doi:10.1038/mt.2012.210

    Article  CAS  Google Scholar 

  72. Jin J, Joo KM, Lee SJ, Jo M-Y, Kim Y, Jin Y, Kim JK, Ahn JM, Yoon M-J, Lim J, Nam D-H (2011) Synergistic therapeutic effects of cytokine-induced killer cells and temozolomide against glioblastoma. Oncol Rep 25:33–39

    PubMed  Google Scholar 

  73. Kong S, Sengupta S, Tyler B, Bais AJ, Ma Q, Doucette S, Zhou J, Sahin A, Carter BS, Brem H, Junghans RP, Sampath P (2012) Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. Clin Cancer Res Off J Am Assoc Cancer Res 18:5949–5960. doi:10.1158/1078-0432.CCR-12-0319

    Article  CAS  Google Scholar 

  74. Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuño MA, Richardson JE, Fan X, Ji J, Chu RM, Bender JG, Hawkins ES, Patil CG, Black KL, Yu JS (2013) Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother CII 62:125–135. doi:10.1007/s00262-012-1319-0

    Article  CAS  PubMed  Google Scholar 

  75. Humphrey PA, Wong AJ, Vogelstein B, Zalutsky MR, Fuller GN, Archer GE, Friedman HS, Kwatra MM, Bigner SH, Bigner DD (1990) Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci U S A 87:4207–4211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Wong AJ, Ruppert JM, Bigner SH, Grzeschik CH, Humphrey PA, Bigner DS, Vogelstein B (1992) Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A 89:2965–2969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, Friedman HS, Gilbert MR, Herndon JE, McLendon RE, Mitchell DA, Reardon DA, Sawaya R, Schmittling RJ, Shi W, Vredenburgh JJ, Bigner DD (2010) Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol Off J Am Soc Clin Oncol 28:4722–4729. doi:10.1200/JCO.2010.28.6963

    Article  Google Scholar 

  78. Sayegh ET, Oh T, Fakurnejad S, Bloch O, Parsa AT (2014) Vaccine therapies for patients with glioblastoma. J Neurooncol 119:531–546. doi:10.1007/s11060-014-1502-6

    Article  CAS  PubMed  Google Scholar 

  79. Bloch O, Crane CA, Fuks Y, Kaur R, Aghi MK, Berger MS, Butowski NA, Chang SM, Clarke JL, McDermott MW, Prados MD, Sloan AE, Bruce JN, Parsa AT (2014) Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial. Neuro-Oncol 16:274–279. doi:10.1093/neuonc/not203

    Article  CAS  PubMed  Google Scholar 

  80. Prados MD, Byron SA, Tran NL, Phillips JJ, Molinaro AM, Ligon KL, Wen PY, Kuhn JG, Mellinghoff IK, de Groot JF, Colman H, Cloughesy TF, Chang SM, Ryken TC, Tembe WD, Kiefer JA, Berens ME, Craig DW, Carpten JD, Trent JM (2015) Toward precision medicine in glioblastoma: the promise and the challenges. Neuro-Oncol 17:1051–1063. doi:10.1093/neuonc/nov031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Cella DF (1996) Quality of life outcomes: measurement and validation. Oncol Williston Park N 10:233–246

    CAS  Google Scholar 

  82. Heimans JJ, Taphoorn MJB (2002) Impact of brain tumour treatment on quality of life. J Neurol 249:955–960. doi:10.1007/s00415-002-0839-5

    Article  PubMed  Google Scholar 

  83. Osoba D, Brada M, Prados MD, Yung WK (2000) Effect of disease burden on health-related quality of life in patients with malignant gliomas. Neuro-Oncol 2:221–228

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Klein M, Taphoorn MJ, Heimans JJ, van der Ploeg HM, Vandertop WP, Smit EF, Leenstra S, Tulleken CA, Boogerd W, Belderbos JS, Cleijne W, Aaronson NK (2001) Neurobehavioral status and health-related quality of life in newly diagnosed high-grade glioma patients. J Clin Oncol Off J Am Soc Clin Oncol 19:4037–4047

    CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Nancy Ann Oberheim Bush & Susan M. Chang

  2. Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Mitchel S. Berger

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  1. Nancy Ann Oberheim Bush
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  2. Susan M. Chang
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  3. Mitchel S. Berger
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Correspondence to Nancy Ann Oberheim Bush.

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Comments

Ryo Nishikawa, Saitama-ken, Japan

In the field of glioma, recent progress of molecular genetics, targeted therapy trials based on the progress of molecular genetics and biology, and, especially, most recent enthusiasm for immunotherapy are watched with keen interest. In this paper, progress of epidemiology, surgery including assistance by imaging and functional monitoring, molecular genetics and histopathology, radiotherapy, chemotherapy, targeted therapies in a separate section from chemotherapy, and immunotherapies of gliomas are summarized. Especially description of targeted therapies and immunotherapies is outstanding, timely, and useful. A brief summary of quality of life is added which makes the paper multidisciplinary indeed.

Manfred Westphal, Hamburg, Germany

Oberheim-Bush and colleagues present a comprehensive overview of the current therapeutic thinking and future strategies for the treatment of gliomas. Such contributions provide a welcome update in a field which is rapidly expanding and fast moving due to the exponentially growing interest in this complex disease, which, however, has not translated into much of a therapeutic advance yet. Some clinical trials still use lomustine which was approved in the 1970s as control arm acknowledging the fact that the extrapolation of therapeutic advances in other cancers has been disappointing at best. The reference to many clinical trials in this article illustrates the breadth of new approaches taken and the recent efforts to improve on clinical trial designs. Integrating large patient data analysis including molecular date and repurposing of drugs should be highlighted as a highly relevant strategy to advance the field. It is very important to the updated readership that with our current nomenclature, we are in the nowhere-land between the older morphological classifications and the inclusion of molecular classifiers which cross the morphological boundaries and it will only be with the much awaited revision of the WHO classification that we find a universally applied language to compare our results and allocate patients to new developments.

It also emerges that treating glioma patients successfully requires a complex infrastructure which allows for maximal data collection via a multitude of modern imaging techniques, and neuropsychological testing, allows for maximal safe resection with an array of intraoperative monitoring and visualization techniques and allows for maximal acquisition of data on the tumor tissue. Due to high degree of interdisciplinary integration and demands on complex infrastructure, this will become increasingly limited to regional centers. Of these, there should be enough so that majority of patients can be followed regularly and preferentially entered into clinical trials without having to travel too far because that impairs their quality of life. The emerging basic principles of modern GBM treatment as they get consolidated in centers of excellence are well updated in this review. The outlook on the field despite all the excitement felt in the translation of molecular insights into clinical application has to be cautionally pessimistic.

Immuno-oncology, as pointed out, offers a vast array of new technologies with CAR cells and the many permutations of vaccination but neuro-oncology has to acknowledge that riding waves as in the past with tyrosine kinase inhibition or anti-angiogenesis is burdened with the fact that gliomas come with an intrinsic neuro-biology which in the past has set frustrating limits to extrapolation.

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Bush, N.A.O., Chang, S.M. & Berger, M.S. Current and future strategies for treatment of glioma. Neurosurg Rev 40, 1–14 (2017). https://doi.org/10.1007/s10143-016-0709-8

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