Diffuse low grade gliomas

Česká verzia

Authors: D. Konečná; D. Netuka
Authors place of work: Neurochirurgická a neuroonkologická klinika 1. LF UK a ÚVN Praha
Published in the journal: Cesk Slov Neurol N 2020; 83/116(5): 467-490
Category: Minimonografie
doi: https://doi.org/10.14735/amcsnn2020467

Summary

Diffuse low grade gliomas (grade II) are heterogenous neuroepithelial tumours, which are known for their infiltrative growth and their distinct histological profile does not match the criteria of the diagnosis of high grade gliomas (grade III, IV). The incidence of diffuse low grade gliomas is significantly lower in comparison to other primary brain tumours. Nevertheless these tumours deserve attention because of their frequent occurence in younger patients and the negative consequences of their biological behaviour in combination with mostly long-term complications associated with oncological treatment. Diagnostics and the individualization of treatment are constantly improving thanks to the ongoing development in the fields of histopathology, cytogenetics and neuroimaging methods. Currently the main treatment option is a radical surgical removal of the tumour with the effort to minimalize the risk of new neurological deficit. Despite the apparently sufficient extent of the resection, further means, such as radiotherapy and/or chemotherapy, are included in the treatment regimen. The timing and modifications of this adjuvant treatment depend on the specific molecular features of the tumour in a combination with other prognostic factors. However, the curability of diffuse low grade gliomas cannot be achieved, mainly due to their infiltrative growth. The main goal of the neurosurgical procedure and oncological treatment is to delay the time to progression and subsequent dediferenciation and thus to prolong the survival of the glioma patients with emphasis on preserving their quality of life. The article aims to summarize current knowledge about diffuse low grade gliomas.

Keywords:

radiotherapy – astrocytoma – surgery – Quality of life – Chemotherapy – seizures – glioma – oligodendroglioma

Zdroje

1. Delgado-López PD, Corrales-García EM, Martino J et al.Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies. Clin Transl Oncol 2017; 19 (8): 931–944. doi: 10.1007/s12094-017-1631-4.

2. Weller M, van den Bent M, Tonn JC et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017; 18 (6): 315–329. doi: 10.1016/S1470-2045 (17) 30194-8.

3. 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 (6): 803–820. doi: 10.1007/s00401-016-1545-1.

4. van den Bent MJ, Afra D, de Witte O et al. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: The EORTC 22845 randomised trial. Lancet 2005; 366 (9490): 985–990. doi: 10.1016/S0140-6736 (05) 67070-5.

5. Baumert BG, Hegi ME, van den Bent MJ et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma: a randomized phase III Intergroup study by EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033). Lancet Oncol 2016; 17 (11): 1521–1532. doi: 10.1016/S1470-2045 (16) 30313-8.

6. Buckner JC, Shaw EG, Pugh SL. Radiation plus procarbazine, CCNU, and vincristine in low- grade glioma. N Engl J Med 2016; 374 (14): 1344–1355. doi: 10.1056/NEJMoa1500925.

7. Leu S, von Felten S, Frank S et al. IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival. Neuro Oncol 2013; 15 (4): 469–479. doi: 10.1093/neuonc/nos317.

8. Stupp R, Mason WP, van der Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10): 987–996. doi: 10.1056/NEJMoa043330.

9. Smits A, Duffau H. Seizures and the natural history of World Health Organization grade II gliomas: a review. Neurosurgery 2011; 68 (5): 1326–1333. doi: 10.1227/NEU.0b013e31820c3419.

10. Koekkoek JA, Kerkhof M, Dirven L et al. Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: a systematic review. Neuro Oncol 2015; 17 (7): 924–934. doi: 10.1093/neuonc/nov032.

11. Ruda R, Bello L, Duffau H et al. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro Oncol 2012; 14: 55–64. doi: 10.1093/neuonc/nos199.

12. Avila EK, Chamberlain M, Schiff D et al. Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro Oncol 2017; 19 (1): 12–21. doi: 10.1093/neuonc/now190.

13. Marson A, Jacoby A, Johnson A et al. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial. Lancet 2005; 365 (9476): 2007–2013. doi: 10.1016/S0140-6736 (05) 66694-9.

14. Plate KH, Wieser HG, Yasargil MG et al. Neuropathological findings in 224 patients with temporal lobe epilepsy. Acta Neuropathol 1993; 86 (5): 433–438. doi: 10.1007/BF00228577.

15. Áfra D, Osztie E, Sipos L et al. Preoperative history and postoperative survival of supratentorial low-grade astrocytomas. Br J Neurosurg 1999; 13 (3): 299–305. doi: 10.1080/02688699943727.

16. Englot DJ, Berger MS, Barbaro NM et al. Predictors of seizure freedom after resection of supratentorial low-grade gliomas. J Neurosurg 2011; 115 (2): 240–244. doi: 10.3171/2011.3.JNS1153.

17. Chang EF, Potts MB, Keles GE et al. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg 2008; 108 (2): 227–235. doi: 10.3171/JNS/2008/108/2/0227.

18. Duffau H, Capelle L, Lopes M et al. Medically intractable epilepsy from insular low-grade gliomas: improvement after an extended lesionectomy. Acta Neurochir (Wien) 2002; 144 (6): 563–573. doi: 10.1007/s00701-002-0941-6.

19. Martino J, Taillandier L, Moritz-Gasser S et al. Re-operation is a safe and effective therapeutic strategy in recurrent WHO grade II gliomas within eloquent areas. Acta Neurochir (Wien) 2009; 151 (5): 427–436. doi: 10.1007/s00701-009-0232-6.

20. Plathow C, Schulz-Ertner D, Thilman C et al. Fractionated stereotactic radiotherapy in low-grade astrocytomas: long-term outcome and prognostic factors. Int J Radiat Oncol Biol Phys 2003; 57 (4): 996–1003. doi: 10.1016/S0360-3016 (03) 00738-7.

21. Scerrati M, Montemaggi P, Iacoangeli M et al. Interstitial brachytherapy for low-grade cerebral gliomas: analysis of results in a series of 36 cases. Acta Neurochir 1994; 131: 97–105. doi: 10.1007/BF01401459.

22. Brada M, Viviers L, Abson C et al. Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann Oncol 2003; 14 (12): 1715–1721. doi: 10.1093/annonc/mdg371.

23. Pace A, Vidiri A, Galié E et al. Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response. Ann Oncol 2003; 14 (12): 1722–1726. doi: 10.1093/annonc/mdg502.

24. Taillandier L, Duffau H. Epilepsy and insular Grade II gliomas: an interdisciplinary point of view from a retrospective monocentric series of 46 cases. Neurosurg Focus 2009; 27 (2): 1–10. doi: 10.3171/2009. 6.FOCUS09102.

25. Koekkoek JA, Dirven L, Heimans JJ et al. Seizure reduction in a low-grade glioma: more than a beneficial side effect of temozolomide. J Neurol Neurosurg Psychiatry 2015; 86 (4): 366–373. doi: 10.1136/jnnp-2014-308136.

26. Hildebrand J, Lecaille C, Perennes J et al. Epileptic seizures during follow-up of patients treated for primary brain tumors. Neurology 2005; 65 (2): 212–215. doi: 10.1212/01.wnl.0000168903.09277.8f.

27. Sherman JH, Moldovan K, Yeoh HK et al. Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J Neurosurg 2011; 114 (6): 1617–1621. doi: 10.3171/2010.12.JNS101602.

28. Abrigo JM, Fountain DM, Provenzale JM et al. Magnetic resonance perfusion for differentiating low-grade from high-grade gliomas at first presentation (Review). Cochrane Database Syst Rev 2018; 1 (1): CD011551. doi: 10.1002/14651858.CD011551.pub2.

29. Fouke SJ, Benzinger T, Gibson D et al. The role of imaging in the management of adults with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2015; 125 (3): 457–479. doi: 10.1007/s11060-015-1908-9.

30. Shah AH, Madhavan K, Heros D et al. The management of incidental low-grade gliomas using magnetic resonance imaging: systematic review and optimal treatment paradigm. Neurosurg Focus 2011; 31 (6): 1–9. doi: 10.3171/2011.9.FOCUS11219.

31. Heiss WD, Raab P, and Lanfermann H. Multimodality assessment of brain tumors and tumor recurrence. J Nucl Med 2011; 52 (10): 1585–1600. doi: 10.2967/jnumed.110.084210.

32. Zhang L, Min Z, Tang M et al. The utility of diffusion MRI with quantitative ADC measurements for differentiating high-grade from low-grade cerebral gliomas: evidence from a meta-analysis. J Neurol Sci 2017; 373: 9–15. doi: 10.1016/j.jns.2016.12.008.

33. Delgado AF, Delgado AF. Discrimination between glioma grades II and III using dynamic susceptibility perfusion MRI: a meta-analysis. Am J Neuroradiol 2017; 38 (7): 1348–1355. doi: 10.3174/ajnr.A5218.

34. Law M, Yang S, Wang H et al. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. Am J Neuroradiol 2003; 24 (10): 1989–1998.

35. Abdullah KG, Lubelski D, Nucifora PGP et al. Use of diffusion tensor imaging in glioma resection. Neurosurg Focus 2013; 34 (4): 1–7. doi: 10.3171/2013.1.FOCUS12412.

36. Wu JS, Zhou LF, Tang WJ et al. 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 2007; 61 (5): 935–949. doi: 10.1227/01.NEU.0000280087.99113.B0.

37. Bello L, Castellano A, Fava E et al. Intraoperative use of diffusion tensor imaging fiber tractography and subcortical mapping for resection of gliomas: technical considerations. Neurosurg Focus 2010; 28 (2): 1–14. doi: 10.3171/2009.12.FOCUS09240.

38. Ius T, Isola M, Budai R et al. Low-grade glioma surgery in eloquent areas: volumetric analysis of extent of resection and its impact on overall survival. A single-institution experience in 190 patients – clinical article. J Neurosurg 2012; 117 (6): 1039–1052. doi: 10.3171/2012.8.JNS12393.

39. Bulik M, Jancalek R, Vanicek J et al. Potential of MR spectroscopy for assessment of glioma grading. Clin Neurol Neurosurg 2013; 115 (2): 146–153. doi: 10.1016/j.clineuro.2012.11.002.

40. Wang Q, Zhang H, Zhang J et al. The diagnostic performance of magnetic resonance spectroscopy in differentiating high-from low-grade gliomas: a systematic review and meta-analysis. Eur Radiol 2016; 26 (8): 2670–2684. doi: 10.1007/s00330-015-4046-z.

41. Bradac O, Vrana J, Jiru F et al. Recognition of anaplastic foci within low-grade gliomas usingMR spectroscopy. Br J Neurosurg 2014; 28 (5): 631–636.doi: 10.3109/02688697.2013.872229.

42. Minn H. PET and SPECT in low-grade glioma. Eur J Radiol 2005; 56 (2): 171–178. doi: 10.1016/j.ejrad.2005.03.020.

43. Dunet V, Pomoni A, Hottinger A et al. Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis. Neuro Oncol 2016; 18 (3): 426–434. doi: 10.1093/neuonc/nov148.

44. Delgado AF, Delgado AF. Discrimination between primary low-grade and high-grade glioma with 11C-methionine PET: a bivariate diagnostic test accuracy meta-analysis. Br J Radiol 2018; 91: 20170426. doi: 10.1259/bjr.20170426.

45. Näslund O, Smits A, Förander P et al. Amino acid tracers in PET imaging of diffuse low-grade gliomas: a systematic review of preoperative applications. Acta Neurochir (Wien) 2018; 160: 1451–1460. doi: 10.1007/s00701-018-3563-3.

46. Kim MM, Lawrence TS, Cao Y. Advances in MR and PET imaging: assessing response in the treatment of low grade glioma. Semin Radiat Oncol 2016; 25 (3): 172–180. doi: 10.1016/j.semradonc.2015.02.003.

47. Rapp M, Floeth FW, Felsberg J et al. Clinical value of O- (2-18 F]-fluoroethyl) -L-tyrosine positron emission tomography in patients with low-grade glioma. Neurosurg Focus 2013; 34 (2): 1–8. doi: 10.3171/2012.12.FOCUS12336.

48. Kunz M, Thon N, Eigenbrod S et al. Hot spots in dynamic18FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neuro Oncol 2011; 13 (3): 307–316. doi: 10.1093/neuonc/noq196.

49. Wyss M, Hofer S, Bruehlmeier M et al. Early metabolic responses in temozolomide treated low-grade glioma patients. J Neurooncol 2009; 95 (1): 87–93. doi: 10.1007/s11060-009-9896-2.

50. Freyschlag CF, Krieg SM, Kerschbaumer J et al. Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging. J Neurooncol 2018; 139 (3): 699–711. doi: 10.1007/s11060-018-2916-3.

51. Cahill DP, Sloan AE, Nahed BV et al. The role of neuropathology in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2015; 125 (3): 531–549. doi: 10.1007/s11060-015-1909-8.

52. Di Carlo DT, Duffau H, Cagnazzo F et al. IDH wild-type WHO grade II diffuse low-grade gliomas. A heterogeneous family with different outcomes. Systematic review and meta-analysis. Neurosurg Rev 2020; 43 (2): 383–395. doi: 10.1007/s10143-018-0996-3.

53. Kramář F, Minárik M, Belšánová B et al. Genetické a epigenetické faktory podmiňující vznik a prognózu mozkových gliomů – souhrn současných poznatků. Cesk Slov Neurol N 2016; 79/112 (4): 400–405. doi: 10.14735/amcsnn2016400.

54. Taylor JW, Chi AS, and Cahill DP. Tailored therapy in diffuse gliomas: using molecular classifiers to optimize clinical management. Oncology 2013; 27 (6): 504–514.

55. Pignatti BF, van der Bent M, Curran D et al. Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 2002; 20 (8): 2076–2084. doi: 10.1200/JCO.2002.08.121.

56. Kazda T, Lakomý R, Poprach A et al. Controversy in the postoperative treatment of low-grade gliomas. Klin Onkol 2017; 30 (5): 337–342. doi: 10.14735/amko2017337.

57. Shaw EG, Berkey BMS. Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg 2008; 109 (5). doi: 10.3171/JNS/2008/109/11/0835.

58. Boissonneau S, Duffau H. Identifying clinical risk in low grade gliomas and appropriate treatment strategies, with special emphasis on the role of surgery. Expert Rev Anticancer Ther 2017; 17 (8): 703–716. doi: 10.1080/14737140.2017.1342537.

59. Jakola AS, Skjulsvik AJ, Myrmel KS et al. Surgical resection versus watchful waiting in low-grade gliomas. Ann Oncol 2017; 28 (8): 1942–1948. doi: 10.1093/annonc/ mdx230.

60. van Thuijl HF, Scheinin I, Sie D et al. Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas. Genome Biol 2014; 15: 1–13. doi: 10.1186/s13059-014-0471-6.

61. Smith JS, Chang EF, Chang SM et al. Role of Extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 2015; 26 (8): 1338–1345. doi: 10.1200/JCO.2007.13.9337.

62. Capelle L, Fontaine D, Mandonnet E et al. Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases. J Neurosurg 2013; 118 (6): 1157–1168. doi: 10.3171/2013.1.JNS121.

63. ChaiChana KL, McGirt MJ, Laterra J et al. Recurrence and malignant degeneration after resection of adult hemispheric low-grade gliomas. Neuro-oncology Surg 2010; 112 (1): 10–17. doi: 10.3171/2008.10.JNS08608.

64. Englot DJ, Berger MS, Barbaro NM et al. Extent of Surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery 2012; 70 (4): 921–928. doi: 10.1227/NEU.0b013e31823c3a30.

65. Ahmadi R, Dictus C, Hartmann C et al. Long-term outcome and survival of surgically treated supratentorial low-grade glioma in adult patients. Acta Neurochir (Wien) 2009; 151: 1359–1365. doi: 10.1007/s00701-009-0435-x.

66. Duffau H, Taillandier L. New concepts in the management of diffuse low-grade glioma: proposal of a multistage and individualized therapeutic approach. Neuro-oncology Surg 2015; 17 (3): 332–342. doi: 10.1093/neuonc/nou153.

67. Schomas DA, Laack NN, Rao RD et al. Intracranial low-grade gliomas in adults: 30-year experience with long-term follow-up at Mayo Clinic. Neuro Oncol 2009; 11: 437–445. doi: 10.1215/15228517-2008-102.

68. Pallud J, Varlet P, Devaux B et al. Diffuse low-grade oligodendrogliomas extend beyond MRI-defined abnormalities. Neurology 2010; 74: 1724–1731.

69. Yordanova YN, Duffau H. Supratotal resection of diffuse gliomas – an overview of its multifaceted implications. Neurochirurgie 2017; 63 (3): 243–249. doi: 10.1016/j.neuchi.2016.09.006.

70. Yordanova YN, Moritz-Gasser S, Duffau H. Awake surgery for WHO grade II gliomas within ‘noneloquent’ areas in the left dominant hemisphere: toward a ‘supratotal’ resection – Clinical article. J Neurosurg 2011; 115 (2): 232–239. doi: 10.3171/2011.3.JNS101333.

71. Duffau H. Long-term outcomes after supratotal resection of diffuse low-grade gliomas: a consecutive series with 11-year follow-up. Acta Neurochir (Wien) 2016; 158: 51–58. doi: 10.1007/s00701-015-2621-3.

72. Uppstrom TJ, Singh R, Hadjigeorgiou GF et al. Repeat surgery for recurrent low-grade gliomas should be standard of care. Clin Neurol Neurosurg 2016; 151: 18–23. doi: 10.1016/j.clineuro.2016.09.013.

73. Duffau H. Is non-awake surgery for supratentorial adult low-grade glioma treatment still feasible? Neurosurg Rev 2018; 41 (1): 133–139. doi: 10.1007/s10143-017-0918-9.

74. De Benedictis A, Moritz-Gasser S, Duffau H. Awake mapping optimizes the extent of resection for low-grade gliomas in eloquent areas. Neurosurgery 2010; 66 (6): 1074–1084. doi: 10.1227/01.NEU.0000369514.74284.78.

75. Chang EF, Clark A, Smith JS et al. Functional mapping-guided resection of low-grade gliomas in eloquent areas of the brain: Improvement of long-term survival – clinical article. J Neurosurg 2011; 114 (3): 566–573. doi: 10.3171/2010.6.JNS091246.

76. De Witt Hamer PC, Robles SG, Zwinderman AH et al. Impact of intraoperative stimulation brain mapping on glioma surgery outcome : a meta-analysis. J Clin Oncol 2014; 30 (2): 2559–2565. doi: 10.1200/JCO.2011.38.4818.

77. Duffau H. Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity. Lancet Neurol 2005; 4: 476–486.

78. Jenkinson MD, Barone DG, Bryant A et al. Intraoperative imaging technology to maximise extent of resection for glioma (Review). Cochrane Database Syst Rev 2018; 1 (1): CD012788. doi: 10.1002/14651858.CD012788.pub2.

79. Liang D, Schulder M. The role of intraoperative magnetic resonance imaging in glioma surgery. Surg Neurol Int 2012; 3: 5320–5327. doi: 10.4103/2152-7806.103029.

80. Wu JS, Gong X, Song YY et al. 3.0-T intraoperative magnetic resonance imaging-guided resection in cerebral glioma surgery: interim analysis of a prospective, randomized, triple-blind, parallel-controlled trial. Neurosurgery 2014; 61 (1): 145–154. doi: 10.1227/NEU.0000000000000372.

81. Edjlali M, Ploton L, Maurage CA et al. Intraoperative MRI and FLAIR analysis: implications for low-grade glioma surgery. J Neuroradiol 2019; S0150-9861 (19) 30448-1. doi: 10.1016/j.neurad.2019.08.005.

82. Pala A, Brand C, Kapapa T et al. The value of intraoperative and early postoperative magnetic resonance imaging in low-grade glioma surgery: a retrospective study. World Neurosurg 2016; 93: 191–197. doi: 10.1016/j.wneu.2016.04.120.

83. Black PM, Alexander E, Martin C et al. Craniotomy for tumor treatment in an intraoperative magnetic resonance imaging unit. Neurosurgery 1999; 45 (3): 423–433. doi: 10.1097/00006123-199909000-00001.

84. Senft C, Bink A, Franz K et al. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 2011; 12 (11): 997–1003. doi: 10.1016/S1470-2045 (11) 70196-6.

85. Leroy HA, Delmaire C, Le Rhun E et al. High-field intraoperative MRI in glioma surgery: a prospective study with volumetric analysis of extent of resection and functional outcome. Neurochirurgie 2018; 64 (3): 155–160. doi: 10.1016/j.neuchi.2018.02.003.

86. Coburger AJ, Nabavi A, König R et al. Contemporary use of intraoperative imaging in glioma surgery: a survey among EANS members. Clin Neurol Neurosurg 2017; 163: 133–141. doi: 10.1016/j.clineuro.2017.10.033.

87. Wang J, Liu X, Ba YM et al. Effect of sonographically guided cerebral glioma surgery on survival time. J Ultrasound Med 2012; 31 (5): 757–762. doi: 10.7863/jum.2012.31.5.757.

88. Bø HK, Solheim O, Kvistad KA et al. Intraoperative 3D ultrasound–guided resection of diffuse low-grade gliomas: radiological and clinical results. J Neurosurg 2019; 132 (2): 518–529. doi: 10.3171/2018.10.jns181290.

89. Ryken TC, Parney I, Buatti J et al. The role of radiotherapy in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2015; 125 (3): 551–583. doi: 10.1007/s11060-015-1948-1.

90. van den Bent M, Afra D, de Witte O et al. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet Neurol 2005; 366: 985–990. doi: 10.1016/S0140-6736 (05) 67070-5.

91. Karim AB, Afra D, Cornu P et al. Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys 2002; 52 (2): 316–324. doi: 10.1016/S0360-3016 (01) 02692-X.

92. Shaw E, Arusell R, Scheithauer B et al. Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a north central cancer treatment group/radiation therapy oncology group/eastern cooperative oncology group study. J Clin Oncol 2002; 20 (9): 2267–2276. doi: 10.1200/JCO.2002.09.126.

93. Karim AB, Maat B, Hatlevoll R et al. A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European organization for research and treatment of cancer (EORTC) study 22844. Int J Radiat Oncol Biol Phys 1996; 36 (3): 549–556. doi: 10.1016/S0360-3016 (96) 00352-5.

94. Thurin E, Nyström PW, Smits A et al. Proton therapy for low-grade gliomas in adults: a systematic review. Clin Neurol Neurosurg 2018; 174: 233–238. doi: 10.1016/j.clineuro.2018.08.003.

95. Shih HA, Sherman JC, Nachtigall LB et al. Proton therapy for low-grade gliomas: results from a prospective trial. Cancer 2015; 121 (10): 1712–1719. doi: 10.1002/cncr.29237.

96. Buckner JC, Pugh SL, Shaw EG et al. Phase III study of radiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low-grade glioma: RTOG 9802 with Alliance, ECOG, and SWOG. J Clin Oncol 2014; 32 (15): 2000. doi: 10.1200/jco.2014.32.15_suppl.2000.

97. Ziu M, Kalkanis SN, Gilbert M et al. The role of initial chemotherapy for the treatment of adults with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J. Neurooncol 2015; 125 (3): 585–607. doi: 10.1007/s11060-015-1931-x.

98. Cairncross G, Wang M, Shaw E et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 2013; 31 (3): 337–343. doi: 10.1200/JCO.2012.43.2674.

99. Donovan LE, Lassman AB. Chemotherapy treatment and trials in low-grade gliomas. Neurosurg Clin N Am 2019; 30 (1): 103–109. doi: 10.1016/j.nec.2018.08.007.

100. van Thuijl HF, Mazor T, Johnson BE et al. Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment. Acta Neuropathol 2015; 129 (4): 597–607. doi: 10.1007/s00401-015-1403-6.

101. Wahl M, Phillips JJ, Molinaro AM et al. Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide. Neuro Oncol 2017; 19 (2): 242–251. doi: 10.1093/neuonc/now176.

102. Shaw EG, Wang M, Coons SW et al. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol 2012; 30 (25): 3065–3070. doi: 10.1200/JCO.2011.35.8598.

103. Fisher BJ, Hu C, Macdonald DR et al. Phase 2 Study of temozolomide-based chemoradiation therapy for high-risk low-grade gliomas: preliminary results of radiation therapy oncology group 0424. Int J Radiat Oncol Biol Phys 2015; 91 (3): 497–504. doi: 10.1016/j.ijrobp.2014.11.012.

104. Reijneveld JC, Taphoorn MJ, Coens C et al. Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 2016; 17 (11): 1533–1542. doi: 10.1016/S1470-2045 (16) 30305-9.

105. van Loon EM, Heijenbrok-Kal MH, van Loon WS et al. Assessment methods and prevalence of cognitive dysfunction in patients with low-grade glioma: a systematic review. J Rehabil Med 2015; 47 (6): 481–488. doi: 10.2340/16501977-1975.

106. Shields LB and Choucair AK. Management of low-grade gliomas: a review of patient-perceived quality of life and neurocognitive outcome. World Neurosurg 2014; 82 (1–2): 299–309. doi: 10.1016/j.wneu.2014.02.033.

107. Tucha O, Smely C, Preier M et al. Cogntive deficits before treatment among patients with brain tumors. Neurosurgery 2000; 47 (2): 324–334. doi: 10.1097/00006123-200008000-00011.

108. McAleer MF, Brown PD. Neurocognitive function following therapy for low-grade gliomas. Semin Radiat Oncol 2015; 25 (3): 210–218. doi: 10.1016/j.semradonc.2015.02.005.

109. Hahn CA, Dunn RH, Logue PE et al. Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors. Int J Radiat Oncol Biol Phys 2003; 55 (4): 992–999. doi: 10.1016/S0360-3016 (02) 04205-0.

110. van Kessel E, Baumfalk AE, van Zandvoort MJ et al. Tumor-related neurocognitive dysfunction in patients with diffuse glioma: a systematic review of neurocognitive functioning prior to anti-tumor treatment. J. Neurooncol 2017; 134 (1): 9–18. doi: 10.1007/s11060-017-2503-z.

111. Schönová K, Weissenberger S, Preiss M et al. Kognitivní funkce u pacientů s nízkostupňovými gliomy – přehledová studie. Cesk Slov Neurol N 2017; 80/113 (4): 396–399. doi: 10.14735/amcsnn2017396.

112. Meador KJ. Cognitive outcomes and predictive factors in epilepsy. Neurology 2002; 58 (8): S21 LP-S26. doi: 10.1212/WNL.58.8_suppl_5.S21.

113. Meador KJ. Cognitive and memory effects ofthe new antiepileptic drugs. Epilepsy Res 2006; 68 (1): 19–94. doi: 10.1016/j.eplepsyres.2005.09.022.

114. Jakola AS, Unsgå G, Solheim O. Quality of life in patients with intracranial gliomas: the impact of modern image-guided surgery. Clinical article. J Neurosurg 2011; 114 (6): 1622–1630. doi: 10.3171/2011.1.JNS101657.

115. Duffau H. Surgery of low-grade gliomas: towards a ‘functional neurooncology. Curr Opin Oncol 2009; 21 (6): 543–549. doi: 10.1097/CCO.0b013e3283305996.

116. Yoshii Y, Tominaga D, Sugimoto K et al. Cognitive function of patients with brain tumor in pre- and postoperative stage. Surg Neurol 2008; 69 (1): 51–61. doi: 10.1016/j.surneu.2007.07.064.

117. Prabhu RS, Won M, Shaw EG et al. Effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: secondary analysis of RTOG 98-02. J Clin Oncol 2014; 32 (6): 535–541. doi: 10.1200/JCO.2013.53.1830.

118. Douw L, Klein M, Fagel SS et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 2009; 8 (9): 810–818. doi: 10.1016/S1474-4422 (09) 70204-2.

119. Gehring K, Sitskoorn MM, Gundy CM et al. Cognitive rehabilitation in patients with gliomas: a randomized, controlled trial. J Clin Oncol 2009; 27 (22): 3712–3722. doi: 10.1200/JCO.2008.20.5765.

120. Sepúlveda-Sánchez JM, Muňoz-Langa J, Arraéz MÁ et al. SEOM clinical guideline of diagnosis and management of low- grade glioma (2017). Clin Transl Oncol 2018; 20 (1): 3–15. doi: 10.1007/s12094-017-1790-3.

121. Sepúlveda-Sánchez JM, Muňoz-Langa J, Arraéz MÁ et al. SEOM clinical guideline of diagnosis and management of low- grade glioma (2017). Clin Transl Oncol 2018; 20 (1): 3–15. doi: 10.1007/s12094-017-1790-3.