Evolution of antitumor treatment for primary glial CNS tumors

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Gliomas are a group of central nervous system (CNS) tumors originating from glial cells. Despite significant efforts in the field of oncology, gliomas, especially high-grade gliomas, remain one of the most complex and aggressive forms of malignancy. Low-grade diffuse gliomas have a relatively favorable prognosis, while high-grade gliomas, especially glioblastomas, are characterized by an extremely unfavorable course. The overall survival (OS) of patients with glioblastoma ranges from 14 to 20 months, and the 5-year survival rate is only 6%. In patients with newly diagnosed glioblastoma, the 6-month progression-free survival (PFS) is approximately 54%, while in relapsed patients, the 6-month PFS is 30–40%, and the 6-month OS is 57%. For newly diagnosed diffuse glial tumors WHO G3–4, the 1-year PFS is approximately 80%, and the median OS is approximately 25 months. These indicators emphasize the need to search for new treatment approaches. This article presents the main current strategies and approaches to the treatment of diffuse glial CNS tumors. A meta-analysis of the efficacy of the combination of bevacizumab and irinotecan was conducted.

About the authors

E. A. Slugina

N.N. Petrov National Medical Research Center of Oncology

Email: emureyko@mail.ru
ORCID iD: 0000-0003-1626-082X
SPIN-code: 2023-1598

Oncologist

Russian Federation, St. Petersburg

V. A. Novik

N.N. Petrov National Medical Research Center of Oncology; Saint Petersburg State Pediatric Medical University

Author for correspondence.
Email: anovik@list.ru
ORCID iD: 0000-0002-2430-4709
SPIN-code: 4549-7885

Dr. Sci. (Med.), Oncologist, Oncoimmunologist, Oncoimmunology Research Department

Russian Federation, St. Petersburg; St. Petersburg

T. L. Nekhaeva

N.N. Petrov National Medical Research Center of Oncology

Email: nehaevat151274@mail.ru
ORCID iD: 0000-0002-7826-4861
SPIN-code: 5366-8969
ResearcherId: (WOS) L-7268-2018

Cand. Sci. (Med.), Head of the Oncoimmunology Research Department

Russian Federation, St. Petersburg

N. A. Efremova

N.N. Petrov National Medical Research Center of Oncology

Email: nataliaavdonkina@gmail.com
SPIN-code: 7352-9350

Cand. Sci. (Med.), Oncologist, Oncoimmunologist, Oncoimmunology Research Department

Russian Federation, St. Petersburg

I. A. Kurnosov

N.N. Petrov National Medical Research Center of Oncology

Email: ivkurnosov@gmail.com
ORCID iD: 0000-0003-2857-8368
SPIN-code: 9131-7381

Cand. Sci. (Med.), Head of the Department of Neuro-Oncology, Junior Researcher, Scientific Department of Neuro-Oncology and Endoscopy

Russian Federation, St. Petersburg

A. B. Danilova

N.N. Petrov National Medical Research Center of Oncology

Email: anovik@list.ru
ORCID iD: 0000-0003-4796-0386
SPIN-code: 9387-8328
Scopus Author ID: 7005563064
ResearcherId: H-7828-2014

Dr. Sci. (Med.), Oncoimmunologist, Senior Reseacher, Oncoimmunology Research Department

Russian Federation, St. Petersburg

I. A. Baldueva

N.N. Petrov National Medical Research Center of Oncology

Email: biahome@mail.ru
ORCID iD: 0000-0002-7472-4613
SPIN-code: 7512-8789

Dr. Sci. (Med.), Chief Researcher, Oncoimmunology Research Department

Russian Federation, St. Petersburg

References

  1. Fisher J.P., Adamson D.C. Current FDA-Approved Therapies for High-Grade Malignant Gliomas. Biomedicines. 2021;9(3). https://dx.doi.org/10.3390/biomedicines9030324
  2. Nieder C., Andratschke N., Wiedenmann N., et al. Radiotherapy for high-grade gliomas. Does altered fractionation improve the outcome? Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al]. 2004;180(7):401–7. https://dx.doi.org/10.1007/s00066-004-1220-7
  3. Mufazalov F.F., Sakaeva D.D., Shtefan A. Radiotherapy of malignant brain gliomas using teniposide. Vopr Onkol. 2008;54(2):208–10.
  4. Bleehen N.M., Stenning S.P. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. Br J Cancer. 1991;64(4):769–74. https://dx.doi.org/10.1038/bjc.1991.396
  5. Tsao M.N., Mehta M.P., Whelan T.J., et al. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma. Int J Radiat Oncol Biol Physics. 2005;63(1):47–55. https://dx.doi.org/10.1016/j.ijrobp.2005.05.024
  6. Rodriguez L.A., Levin V.A. Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Williston Park, NY). 1987;1(9):29–36.
  7. Hochberg F.H., Linggood R., Wolfson L., et al. Quality and duration of survival in glioblastoma multiforme. Combined surgical, radiation, and lomustine therapy. JAMA. 1979;241(10):1016–8.
  8. Walker M.D., Alexander E., Jr., Hunt W.E., et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978;49(3):333–43. https://dx.doi.org/10.3171/jns.1978.49.3.0333
  9. Levin V.A., Silver P., Hannigan J., et al. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Physics. 1990;18(2):321–4. https://dx.doi.org/10.1016/0360-3016(90)90096-3
  10. Westphal M., Hilt D.C., Bortey E., et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncology. 2003;5(2):79–88. https://dx.doi.org/10.1093/neuonc/5.2.79
  11. Stupp R., Mason W.P., van den Bent M.J., et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New Engl J Med. 2005;352(10):987–96. https://dx.doi.org/10.1056/NEJMoa043330
  12. Cohen M.H., Shen Y.L., Keegan P., Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. The oncologist. 2009;14(11):1131–8. https://dx.doi.org/10.1634/theoncologist.2009-0121
  13. Scherm A., Ippen F.M., Hau P., et al. Targeted therapies in patients with newly diagnosed glioblastoma-A systematic meta-analysis of randomized clinical trials. Int J Cancer. 2023;152(11):2373–82. https://dx.doi.org/10.1002/ijc.34433 URL: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34433?download=true
  14. Kreisl T.N., 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.: Official J Am Soc Clin Oncol. 2009;27(5):740–5. https://dx.doi.org/10.1200/jco.2008.16.3055
  15. Vredenburgh J.J., Desjardins A., Herndon J.E., et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol.: Official J Am Soc Clin Oncol. 2007;25(30):4722–9. https://dx.doi.org/10.1200/jco.2007.12.2440
  16. Murray L.J., Bridgewater C.H., Levy D. Carboplatin chemotherapy in patients with recurrent high-grade glioma. Clin Oncol. (Great Br). 2011;23(1):55–61. https://dx.doi.org/10.1016/j.clon.2010.09.007
  17. Leonard A., Wolff J.E. Etoposide improves survival in high-grade glioma: a meta-analysis. Anticancer Res. 2013;33(8):3307–15.
  18. Bokstein F., Blumenthal D., Limon D., et al. Concurrent Tumor Treating Fields (TTFields) and Radiation Therapy for Newly Diagnosed Glioblastoma: A Prospective Safety and Feasibility Study. Front Oncol. 2020;10:411. https://dx.doi.org/10.3389/fonc.2020.00411
  19. Birk H.S., Han S.J., Butowski N.A. Treatment options for recurrent high-grade gliomas. CNS Oncology. 2017;6(1):61–70. https://dx.doi.org/10.2217/cns-2016-0013
  20. Cairncross J.G., Ueki K., Zlatescu M.C., et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J National Cancer Institute. 1998;90(19):1473–9. https://dx.doi.org/10.1093/jnci/90.19.1473
  21. Friedman H.S., Prados M.D., Wen P.Y., et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol.: Official J Am Soc Clin Oncol. 2009;27(28):4733–40. https://dx.doi.org/10.1200/jco.2008.19.8721.
  22. Насхлеташвили Д.Р. Горбунова В.А., Бычков М.Б. и др. Бевацизумаб в сочетании с иринотеканом в лечении рецидивов глиобластом. Опухоли головы и шеи. 2012;3:56–9. [Naskhletashvili D.R. Gorbunova V.A., Bychkov M.B., et al. Bevacizumab in combination with irinotecan in the treatment of recurrent glioblastomas. Opukh Golovy Shei. 2012;3:56–9. (In Russ.)].
  23. Wick W., Gorlia T., Bendszus M., et al. Lomustine and Bevacizumab in Progressive Glioblastoma. New Engl J Med. 2017;377(20):1954–63. https://dx.doi.org/10.1056/NEJMoa1707358
  24. Buckner J.C., Shaw E.G., Pugh S.L., et al. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. New Engl J Med. 2016;374(14):1344–55. https://dx.doi.org/10.1056/NEJMoa1500925
  25. Mellinghoff I.K., van den Bent M.J., Blumenthal D.T., et al. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. New Engl J Med. 2023;389(7):589–601. https://dx.doi.org/10.1056/NEJMoa2304194
  26. Minniti G., Lombardi G., Paolini S. Glioblastoma in Elderly Patients: Current Management and Future Perspectives. Cancers. 2019;11(3). https://dx.doi.org/10.3390/cancers11030336
  27. Md J.R.P., O’Callaghan C.J., Ding K., et al. A Phase Iii Randomized Controlled Trial of Short-Course Radiotherapy with or without Concomitant and Adjuvant Temozolomide in Elderly Patients with Glioblastoma (Ncic Ctg Ce.6, Eortc 26062-22061, Trog 08.02, Nct00482677). Neuro Oncol. 2014;16(Suppl. 3):iii46. https://dx.doi.org/10.1093/neuonc/nou209.16
  28. Hegi M.E., Diserens A.C., Gorlia T., et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. New Engl J Med. 2005;352(10):997–1003. https://dx.doi.org/10.1056/NEJMoa043331
  29. Yu W., Zhang L., Wei Q., Shao A. O(6)-Methylguanine-DNA Methyltransferase (MGMT): Challenges and New Opportunities in Glioma Chemotherapy. Front Oncol. 2019;9:1547. https://dx.doi.org/10.3389/fonc.2019.01547
  30. Tzaridis T., Schäfer N., Weller J., et al. MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA-09 trial. Int J Cancer. 2021;148(7):1695–707. https://dx.doi.org/10.1002/ijc.33363
  31. Jacobson P.D., Gostin L.O. Restoring Health to Health Reform. Jama. 2010;304(1):85–6. https://dx.doi.org/10.1001/jama.2010.917
  32. Choi H.J., Choi S.H., You S.H., et al. MGMT Promoter Methylation Status in Initial and Recurrent Glioblastoma: Correlation Study with DWI and DSC PWI Features. AJNR Am J Neuroradiol. 2021;42(5):853–60. https://dx.doi.org/10.3174/ajnr.A7004
  33. Guo X., Shi Y., Liu D., et al. Clinical updates on gliomas and implications of the 5th edition of the WHO classification of central nervous system tumors. Front Oncol. 2023;13. https://dx.doi.org/10.3389/fonc.2023.1131642 URL: https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1131642
  34. Olar A., Wani K.M., Alfaro-Munoz K.D., et al. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol. 2015;129(4):585–96. https://dx.doi.org/10.1007/s00401-015-1398-z
  35. Guo C., Pirozzi C.J., Lopez G.Y., Yan H. Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target. Curr Opin Neurol. 2011;24(6):648–52. https://dx.doi.org/10.1097/WCO.0b013e32834cd415
  36. Fontaine D., Vandenbos F., Lebrun C., et al. Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice. Rev Neurolog. 2008;164(6–7):595–604. https://dx.doi.org/10.1016/j.neurol.2008.04.002
  37. Guo X S.Y., Liu D, Li Y, Chen W. et al. Clinical updates on gliomas and implications of the 5th edition of the WHO classification of central nervous system tumors. Front Oncol. 2023;13:1131642. https://dx.doi.org/doi: 10.3389/fonc.2023.1131642
  38. Wick W., Hartmann C., Engel C., et al. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol.: Official J Am Soc Clin Oncol. 2009;27(35):5874–80. https://dx.doi.org/10.1200/jco.2009.23.6497
  39. Чижова К.А. Гуляев Д.А., Чиркин В.Ю., Курносов И.А. Влияние объема резекции глиобластомы IDH-wildtype на выживаемость. Вопросы онкологии. 2025;71(5). [Chizhova K.A. Gulyaev D.A., Chirkin V.Yu., Kurnosov I.A. Influence of Extent of IDH Wild-Type Glioblastoma Resection on Survival. Vopr Onkol. 2025;71(5) (In Russ)]. https://dx.doi.org/10.37469/0507-3758-2025-71-5-OF-227
  40. AbdelFatah M.A.R., Kotb A., Said M.A., Abouelmaaty E.M.H. Impact of extent of resection of newly diagnosed glioblastomas on survival: a meta-analysis. Egypt J Neurosurg. 2022;37(1):3. https://dx.doi.org/ 10.1186/s41984-022-00145-1
  41. Mellinghoff I.K., Ellingson B.M., Touat M., et al. Ivosidenib in Isocitrate Dehydrogenase 1-Mutated Advanced Glioma. J Clin Oncol.: Official J Am Soc Clin Oncol. 2020;38(29):3398–406. https://dx.doi.org/10.1200/jco.19.03327
  42. Lei J., Liu Y., Fan Y. The effects of dabrafenib and/or trametinib treatment in Braf V600-mutant glioma: a systematic review and meta-analysis. Neurosurg Rev. 2024;47(1):458. https://dx.doi.org/ 10.1007/s10143-024-02664-x
  43. Reardon D.A., Brandes A.A., Omuro A., et al. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA. Oncology. 2020;6(7):1003–10. https://dx.doi.org/10.1001/jamaoncol.2020.1024
  44. de Groot J., Penas-Prado M., Alfaro-Munoz K., et al. Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. Neuro-oncology. 2020;22(4):539–49. https://dx.doi.org/10.1093/neuonc/noz185
  45. Desjardins A., Gromeier M., Herndon J.E., et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus. New Engl J Med. 2018;379(2):150–61. https://dx.doi.org/10.1056/NEJMoa1716435
  46. Lv L., Huang J., Xi H., Zhou X. Efficacy and safety of dendritic cell vaccines for patients with glioblastoma: A meta-analysis of randomized controlled trials. Int Immunopharmacol. 2020;83:106336. https://dx.doi.org/10.1016/j.intimp.2020.106336
  47. Liau L.M., Ashkan K., Tran D.D., et al. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Translat Med. 2018;16(1):142. https://dx.doi.org/10.1186/s12967-018-1507-6
  48. Liau L.M., Ashkan K., Brem S., et al. Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial. JAMA. Oncology. 2023;9(1):112–21. https://dx.doi.org/10.1001/jamaoncol.2022.5370 URL: https://jamanetwork.com/journals/jamaoncology/articlepdf/2798847/jamaoncology_liau_2022_oi_220066_1674054620.80001.pdf
  49. Sampson J.H., Heimberger A.B., Archer G.E., et al. 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.: Official J Am Soc Clin Oncol. 2010;28(31):4722–9. https://dx.doi.org/10.1200/jco.2010.28.6963
  50. Sampson J.H., Aldape K.D., Archer G.E., et al. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Neuro-oncology. 2011;13(3):324–33. https://dx.doi.org/10.1093/neuonc/noq157
  51. Schuster J., Lai R.K., Recht L.D., et al. A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study. Neuro-oncology. 2015;17(6):854–61. https://dx.doi.org/10.1093/neuonc/nou348
  52. Weller M., Butowski N., Tran D.D., et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. The Lancet Oncology. 2017;18(10):1373–85. https://dx.doi.org/10.1016/s1470-2045(17)30517-x
  53. Maalej K.M., Merhi M., Inchakalody V.P., et al. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances. Mol Cancer. 2023;22(1):20. https://dx.doi.org/10.1186/s12943-023-01723-z

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).