The phenomenon of long-term survival of patients with supratentorial glioblastomas: features of complex treatment and neuroimaging data

Background. Glioblastoma is the most common primary malignant brain tumor with an extremely unfavorable prognosis. The frequency of the “longevity” phenomenon (>3 years of overall survival – OS) in this disease is 5–10 %. The reasons for the more favorable prognosis in these patients are still unclear.

Aim. To compare the clinical and MRI data as well as features of complex treatment of patients with supratentorial glioblastomas among the control group (OS <2 years) and study group (with the phenomenon of “longevity”, OS >3 years).

Material and methods. This study included 41 patients with hemispheric glioblastomas: 17 with the “longevity” phenomenon (study group – long-term survival (LTS), prospective set); 24 patients in the control group (retrospective set). Taking into account the average age of patients, the following MRI features were examined: tumor localization relative to the frontal lobe; invasion of deep brain structures; the ratio of contrastenhancing and non-contrast-enhancing parts of the glioma; tumor contrast intensity; localization of recurrent tumor (local / distant) in case of  disease progression. Comparative analysis of complex treatment took into account the following parameters: the number of chemotherapy (ChT) courses and radiation regimens after the 1^st operation and after disease recurrence; the fact and number of repeated tumor resections after recurrence; the presence of IDH1 mutation.

Results. The localization of the lesion relative to the frontal lobe, the number of affected lobes of the brain and the invasion of deep structures did not differ significantly in the examined groups. Patients of study group (LTS, prospective set) were significantly younger than the patients of the control group (p <0.05). The tendency towards a single-lobe lesion was noted in the LTS group (p = 0.085). The average volume of the contrast-enhancing part of the tumor (according to MRI data in the T1 mode) in patients of LTS group was 34 cm³, and the non-contrast-enhancing part (in the T2-FLAIR mode) was 105 cm³, the ratio was 1: 3 (p >0.05). The tumor contrast intensity was 1.5 in average compared to the intact cerebral hemisphere. Among patients of LTS group, 8 patients (47 %) were re-operated due to disease recurrence, while in the control group there were no repeated operations (p <0.05). The results of the analysis of radiation therapy after the 1^st operation were the follows: for LTS patients the median total radiation dose (TRD) was 58 (35–66) Gy, with no significant differences between the groups (p >0.05); the number of temozolomide courses in the LTS group were 9 (6–22), while in the control group it was 6 (3–10), p <0.05. The repeated radiotherapy (RT) in different regimens was applied in the LTS group in 52 % of patients, in the control group – 0 (p <0.05). The repeated ChT (17 (9–23) courses, mainly with bevacizumab) was applied in the LTS group in 65 % of patients, in the control group – 0 (p <0.05). The IDH1 mutation was studied only in 15 patients: positive – in 1 (LTS group); negative – in 14 patients (7 from the control group).

Conclusion. The following significant differences were revealed: patients with supratentorial glioblastomas were younger in the LTS group. The important features of the complex treatment of patients in LTS group included statistically higher frequency of repeated resections in case of recurrence (47 %) and repeated sessions of radiotherapy (RT) in various modes (52 %); significantly more aggressive and prolonged ChT (with the predominance of temozolomide in the 1^st line of treatment and bevacizumab in case of recurrence). There were no significant differences between two examined groups in tumor localization, intensity of its contrasting, the ratio of contrasted and non-contrast parts of the tumor, invasion of deep structures of the brain, involvement of functionally significant areas (FSA).

1. Jiang H., Zeng W., Ren X. et al. Super-early initiation of temozolomide prolongs the survival of glioblastoma patients without gross-total resection: A retrospective cohort study. J Neurooncol 2019;144(1):127–35. DOI: 10.1007/s11060-019-03211-1

2. Tamimi A.F., Juweid M. Epidemiology and outcome of glioblastoma. Chapter 8. In: Glioblastoma. Ed. by S. De Vleeschouwer. Brisbane (AU): Codon Publications, 2017. DOI: 10.15586/codon.glioblastoma.2017.ch8

3. Goryainov S.A., Goldberg M.F., Golanov A.V. et al. The phenomenon of long-term survival in glioblastoma patients. Part I: the role of clinical and demographic factors and an IDH1 mutation (R 132 H). Zhurnal voprosy neirokhirurgii im. N.N. Burdenko = Burdenko’s Journal of Neurosurgery 2017;81(3):5–16. (In Russ.). DOI: 10.17116/neiro20178135-16

4. Primary tumors of the central nervous system: Clinical guidelines. Moscow, 2020. Available at: https://ruans.org/Text/Guidelines/primary-tumors-of-cns-2020.pdf. (In Russ.).

5. Matsko M.V., Matsko D.E., Volkov N.M. et al. Morphological and molecular genetic features of primary glioblastomas in patients with unusually high life expectancy. Sibirskii onkologicheskii zhurnal = Siberian journal of oncology 2019;18(3):34–44. (In Russ.). DOI: 10.21294/1814-4861-2019-18-3-34-44

6. Barbagallo G.M., Paratore S., Caltabiano R. et al. Long-term therapy with temozolomide is a feasible option for newly diagnosed glioblastoma: A single-institution experience with as many as 101 temozolomide cycles. Neurosurg Focus 2014;37(6):E4. DOI: 10.3171/2014.9.FOCUS14502

7. Park J.K., Hodges T., Arko L. et al. Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol 2010;28(24):3838–43. DOI: 10.1200/JCO.2010.30,0582

8. Johnston A., Creighton N., Parkinson J. et al. Ongoing improvements in postoperative survival of glioblastoma in the temozolomide era: a population-based data linkage study. Neurooncol Pract 2020;7(1):22–30. DOI: 10.1093/nop/npz021

9. Kobyakov G.L., Absalyamova O.V., Anikeeva O.Yu. et al. Practical recommendations for drug treatment of primary tumors of the central nervous system. Malignant tumours 2015;(4s):55–79. (In Russ.). DOI: 10.18027/2224-5057-2015-4s-55-79

10. Golanov A.V. Glioblastomas of the cerebral hemispheres: results of combined treatment and factors affecting prognosis. Abstract of the dis. ... of doctor of med. sciences. Moscow, 1999. (In Russ.).

11. Kobyakov G.L., Absalyamova O.V., Urakov S.V. et al. Antiangiogenic therapy in glioblastoma treatment: review and personal experience. Sovremennaya onkologiya = Journal of Modern Oncology 2009;(1):17–24. (In Russ.).

12. Kobyakov G.L., Smolin A.V., Bekyashev A.Kh. et al. Treatment of recurrent glioblastoma: is there any success? Opukholi golovy i shei = Head and Neck Tumors (HNT) 2014;(3):12–21. (In Russ.). DOI: 10.17650/2222-1468-2014-0-3-872-878

13. Kobyakov G.L., Absalyamova O.V., Bekyashev A.Kh. et al. Practical guidelines for drug treatment of primary tumors of the central nervous system. Malignant tumours 2020;10(3s2–1):109–33. (In Russ.). DOI: 10.18027/2224-5057-2020-10-3s2-07

14. Kim I.H. Appraisal of re-irradiation for the recurrent glioblastoma in the era of MGMT promotor methylation. Radiat Oncol J 2019;37(1):1–12. DOI: 10.3857/roj.2019.00171

15. Matsko M.V., Sklyar S.S., Ulitin A.Yu. et al. Changes in the MGMT gene expression in patients with primary glioblastoma after relapse. Influence of clinical characteristics and MGMT expression on survival of patients. Sibirskii onkologicheskii zhurnal = Siberian journal of oncology 2021;(3):5–17. (In Russ.). DOI: 10.21294/1814-4861-2021-20-3-5-17

16. Stark A.M., van de Bergh J., Hedderich J. et al. Glioblastoma: clinical characteristics, prognostic factors and survival in 492 patients. Clin Neurol Neurosurg 2012;114(7):840–5. DOI: 10.1016/j.clineuro.2012.01.026

17. Brown N.F., Ottaviani D., Tazare J. et al. Survival outcomes and prognostic factors in glioblastoma. Cancers (Basel) 2022;14(13):3161. DOI: 10.3390/cancers14133161

18. Mukherjee S., Wood J., Liaquat I. et al. Craniotomy for recurrent glioblastoma: Is it justified? A comparative cohort study with outcomes over 10 years. Clin Neurol Neurosurg 2020;188:105568. DOI: 10.1016/j.clineuro.2019.105568

19. Sanai N., Snyder L.A., Honea N.J. et al. Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas. J Neurosurg 2011;115(4):740–8. DOI: 10.3171/2011.6.JNS11252

20. Kaneko S., Eljamel M.S. Fluorescence image-guided neurosurgery. Future Oncology 2017;13(26):2341–8. DOI: 10.2217/fon-2017-0194

21. Solomons M.R., Jaunmuktane Z., Weil R.S. et al. Seizure outcomes and survival in adult low-grade glioma over 11 years: living longer and better. Neurooncol Pract 2020;7(2):196–201. DOI: 10.1093/nop/npz056

22. Scherer H.J. A critical review: The pathology of cerebral gliomas. J Neurol Psychiatry 1940;3(2):147–77. DOI: 10.1136/jnnp.3.2.147

23. Halperin E.C., Burger P.C., Bullard D.E. The fallacy of the localized supratentorial malignant glioma. Int J Radiat Oncol Biol Phys 1988;15(2):505–9. DOI: 10.1016/s0360-3016(98)90036-0

24. Parsa A.T., Wachhorst S., Lamborn K.R. et al. Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults. J Neurosurg 2005;102(4):622–8. DOI: https://doi.org/10.3171/jns.2005.102.4.0622

25. Jakola A.S., Bouget D., Reinertsen I. et al. Spatial distribution of malignant transformation in patients with low-grade glioma. J Neurooncol 2020;146(2):373–80. DOI: 10.1007/s11060-020-03391-1

26. Lasocki A., Gaillard F. Non-contrast-enhancing tumor: A new frontier in glioblastoma research. AJNR Am J Neuroradiol 2019;40(5):758–65. DOI: 10.3174/ajnr.A6025

27. Boxerman J.L., Zhang Z., Safriel Y. et al. Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIn 6686. Neuro Oncology 2018;20(10):1400–10. DOI: 10.1093/neuonc/noy049

28. Fyllingen E.H., Bø L.E. Survival of glioblastoma in relation to tumor location: a statistical tumor atlas of a population-based cohort. Acta Neurochirurg 2021;163:1895–905. DOI: 10.1007/s00701-021-04802-6

29. Armocida D., Pesce A., Palmieri M. Periventricular zone involvement as a predictor of survival in glioblastoma patients: A single centre cohort-comparison investigation concerning a distinct clinical entity. Interdisc Neurosurg 2021;25:101185. DOI: 10.1016/j.inat.2021.101185

30. Friedlein K., Bozhkov Y., Hore N. et al. A new functional classification system (FGA/B) with prognostic value for glioma patients. Sci Rep 2015;(5):12373. DOI: 10.1038/srep12373

31. Jovčevska I. Genetic secrets of long-term glioblastoma survivors. Bosn J Basic Med Sci 2019;19(2):116–24. DOI: 10.17305/bjbms.2018.3717