Results of microsurgical resection of glioblastomas under endoscopic and fluorescent control

Overall survival and recurrence-free survival (RFS) in patients with glioblastoma directly depend on the radicality of tumor resection. According to a number of literature sources, it is known that endoscopic surgeries under fluorescence control increase the rate of total resection. However, until now, there is little data on whether endoscopic resection with fluorescence control affects RFS and overall survival of patients with glioblastoma. The aim of our study was to investigate the effect of intraoperative endoscopic and fluorescence control on overall survival and RFS in patients with glioblastoma. A retrospective single-center analysis was performed in 20 patients with glioblastoma. Ten patients underwent tumor resection using an operating microscope with endoscopic and fluorescence control. In 5 patients, 5-aminolevulinic acid (5-ALA) (alasens) at a dose of 20 mg/ kg was used as a photosensitizer, in 5 patients, chlorin e6 (photoditazine) at a dose of 1 mg/kg. Ten patients underwent resection under endoscopic control, but without fluorescence control. Both cohorts of patients were comparable in age, functional status, tumor localization, adjuvant treatment methods, and molecular status. The criteria for assessing the effectiveness of the study in the groups were: the radicality of the surgical intervention according to postoperative magnetic resonance imaging with contrast enhancement, as well as the median RFS and OS in patients. In the group of combined surgery under microscopic and fluorescence control with an endoscope, the rate of total tumor resection was higher than in the group of patients who underwent only surgery under a microscope and an endoscope without fluorescence control (100% versus 60%; p = 0.002). Median OS (20.2 months (95% CI 11.9-28.6) versus 16.3 months (95% CI 11.0-20.9); (p = 0.003)) and median RFS (11.7 months (95% CI 9.8-15.7) versus 9.8 months (95% CI 6.1-13.4) (p = 0.04)), were also statistically significantly higher compared to the group of patients who received treatment to the same extent, but without fluorescence control. As our experience has shown, the use of fluorescence control during tumor resection in patients with glioblastoma with endoscopic assistance is certainly necessary, given the technical capabilities available, as it has a positive effect on the treatment results for this category of patients.

1. Rynda A.Yu., Olyushin V.E., Rostovtsev D.M., et al. Intraoperative photodynamic therapy in complex treatment of malignant gliomas. Zhurnal Voprosy Neirokhirurgii Imeni N.N. Burdenko, 2023, vol. 87(1), pp.25-34. (In Russian) doi:10.17116/neiro20238701125

2. Rynda A.Yu., Olyushin V.E., Rostovtsev D.M., et al. Intraoperative fluorescence control with chlorin E6 in resection of glial brain tumors. Zhurnal Voprosy Neirokhirurgii Imeni N.N. Burdenko, 2021, vol.85, no.4, pp. 20-28. (In Russian). doi:10.17116/neiro20218504120

3. Rynda A.Y., Rostovthev D.M., Zabrodskaya Y.M., et al. Immunotherapy with autologous dendritic cells in the complex treatment of malignant gliomas – results.J. Neurooncol., 2024, vol.166, pp.309-319. doi: 10.1007/s11060-023-04559-1

4. Rynda A.Y., Olyushin, V., Rostovtsev D. Immunotherapy With Autological Dendritic Cells in the Structure of Complex Treatment of Gliomas. Neurosurgery, 2024, vol.70 (1), pp.196. doi: 10.1227/neu.0000000000002809_1244

5. Rynda A.Yu., Rostovtsev D.M., Olyushin V.E., Zabrodskaya YuM. Therapeutic pathomorphosis in malignant glioma tissues after photodynamic therapy with сhlorin e6 (reports of two clinical cases). Biomedical Photonics, 2020, vol.9(2), pp.45-54. (In Russian) doi: 10.24931/2413–9432–2020–9–2–45–54

6. Ostrom Q.T., Cioffi G., Waite K., et al. CBTRUS Statistical Report: primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol., 2021, vol.23, pp. III1–III105. doi: 10.1093/NEUONC/NOAB200

7. Poon M.T.C., Sudlow C.L.M., Figueroa J.D., Brennan P.M. Longer-term (≥2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: A systematic review and meta-analysis. Sci Rep., 2020, vol.10, pp.11622. doi: 10.1038/s41598-020-68011-4

8. Karschnia P., Vogelbaum M.A., van den Bent M., et al. Evidence-based recommendations on categories for extent of resection in diffuse glioma. Eur J Cancer., 2021, vol.149, pp.23-33. doi: 10.1016/j.ejca.2021.03.002

9. Rynda A.Yu., Olyushin V.E., Rostovtsev D.M., et al. Comparative analysis of 5-ALA and chlorin E6 fluorescence-guided navigation in malignant glioma surgery. Pirogov Russian Journal of Surgery = Khirurgiya. Zurnal im. N.I. Pirogova, 2022, vol.1, pp.5-14. (In Russian) doi: 10.17116/hirurgia20220115

10. Goryaynov S.A., Potapov A.A., Okhlopkov V.A., et al. Metabolic navigation during brain tumor surgery: analysis of a series of 403 patients. Russian journal of neurosurgery, 2022, vol.24(4), pp.46-58. doi:10.17650/1683-3295-2022-24-4-46-58

11. Rynda A.Yu., Zabrodskaya Yu.M., Olyushin V.E., et al. Morphological evaluation of the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas. Arkhiv Patologii, 2021, vol.83(5), pp.13-20. (In Russian) doi: 10.17116/patol20218305113

12. Goryaynov S.A., Buklina S.B., Khapov I.V., et al. 5-ALA-guided tumor resection during awake speech mapping in gliomas located in eloquent speech areas: Single-center experience. Front. Oncol., 2022, vol.12, pp.940951. doi: 10.3389/fonc.2022.940951

13. Rynda A.Yu., Rostovtsev D.M., Olyushin V.E. Fluorescence-Guided Resection of Glioma – literature review. Russian Neurosurgical Journal named after professor A.L. Polenov, 2018, vol.X(1), pp. 97-110. (In Russian)

14. Batalov A.I., Goryaynov S.A., Zakharova N.E., et al. Prediction of Intraoperative Fluorescence of Brain Gliomas: Correlation between Tumor Blood Flow and the Fluorescence. J. Clin. Med., 2021, vol.10, pp. 2387. doi: 10.3390/jcm10112387

15. Rynda A.Yu., Olyushin V.E., Rostovtsev D.M., et al. Fluorescent diagnostics with chlorin e6 in surgery of low-grade glioma. Biomedical Photonics, 2021, vol. 10, no. 4, pp. 35-43 (in Russian). doi: 10.24931/2413–9432–2021–10-4-35-43

16. Potapov A.A., Chobulov S.A., Nikitin P.V., et al. Intraoperative vascular fluorescence in cerebral glioblastomas and vascular histological features. Zhurnal Voprosy Neirokhirurgii Imeni N.N. Burdenko, 2019, vol.83(6), pp.21-34. (In Russian). doi: 10.17116/neiro20198306121

17. Rynda A.Yu., Rostovtsev D.M., Olyushin V.E., Zabrodskaya Yu.M. Fluorescence-guided resection of glioma using «photoditazin». Grekov’s Bulletin of Surgery, 2017, vol.176(5), pp.10-15. (In Russian). doi: 10.24884/0042-4625-2017-176-5-10-15

18. Goryaynov S.A., Okhlopkov V.A., Golbin D.A., et al. Fluorescence Diagnosis in Neurooncology: Retrospective Analysis of 653 Cases. Front. Oncol., 2019, vol.9, pp.830. doi: 10.3389/fonc.2019.00830

19. Stummer W., Pichlmeier U., Meinel T., et al. ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol., 2006, vol.7(5), pp.392-401. doi: 10.1016/S1470-2045(06)70665-9

20. Goriaĭnov S.A., Potapov A.A., Pitskhelauri D.I., et al. Intraoperative fluorescence diagnostics upon recurrent operations for brain gliomas. Zhurnal Voprosy Neirokhirurgii Imeni N.N. Burdenko, 2014, vol.78(2), pp.22-31. (In Russian).

21. Rynda A., Olyushin V., Rostovtsev D. Fluorescence navigation in glioma surgery using 5 ALA and chlorin E6. Neuro-Oncology, 2021, vol.23(2), pp. ii25. doi: 10.1093/neuonc/noab180.086

22. Rapp M., Kamp M., Steiger H.J., Sabel M. Endoscopic-assisted visualization of 5-aminolevulinic acid-induced fluorescence in malignant glioma surgery: a technical note. World Neurosurg., 2014, vol.82, ppe277–e279. doi: 10.1016/j.wneu.2013.07.002

23. Potapov A.A., Usachev D.J., Loshakov V.A., et al. First experience in 5-ALA fluorescence-guided and endoscopically assisted microsurgery of brain tumors. Medical Laser Application, 2008, vol.23(4), pp. 202-208. doi: 10.1016/j.mla.2008.07.006

24. Bettag C., Schatlo B., Abboud T. et al. Endoscope-enhanced fluorescence-guided microsurgery increases survival in patients with glioblastoma. Acta Neurochir (Wien), 2023, vol.165(12), pp.4221-4226. doi: 10.1007/s00701-023-05862-6

25. Bettag C., Schregel K., Langer P., et al. Endoscope-assisted fluorescence-guided resection allowing supratotal removal in glioblastoma surgery. Neurosurg Focus, 2021, vol.50: pp. E3. doi: 10.3171/2020.10.FOCUS20560.

26. Strickland B.A., Zada G. 5-ALA Enhanced Fluorescence – Guided Microscopic to Endoscopic Resection of Deep Frontal Subcortical Glioblastoma Multiforme. World Neurosurgery, 2021, vol.148, pp. 65. doi: 10.1016/j.wneu.2020.12.168

27. Sakata T., Tanikawa M., Yamada H. Minimally invasive treatment for glioblastoma through endoscopic surgery including tumor embolization when necessary: a technical note. Front Neurol., 2023, vol.14, pp.1170045. doi: 10.3389/fneur.2023.1170045

28. Ma R., Livermore L.J., Taylor L. et al. Endoscopic 5-Aminolevulinic Acid – Induced Fluorescence-Guided Intraparenchymal Brain Tumor Resection – Can the Endoscope Detect More Fluorescence Than the Microscope? World Neurosurgery, 2024, vol.185, pp. e1268-e1279. doi: 10.1016/j.wneu.2024.03.067

29. Takeda J., Nonaka M., Li Y., et al. 5-Aminolevulinic acid fluorescence-guided endoscopic surgery for intraventricular tumors. Surg Neurol Int., 2022, vol.13, pp. 302. doi: 10.25259/SNI_488_2022

30. McKinnon C., Voets N., Livermore L., et al. Endoscopic ipsilateral interhemispheric approach for resection of selected deep medial brain tumors. World Neurosurg., 2020, vol.144, pp.162-169. doi: 10.1016/j.wneu.2020.08.147

31. Louis D.N., Perry A., Wesseling P., et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol., 2021, vol.23(8), pp.1231-1251. doi: 10.1093/neuonc/noab106

32. Stupp R., Mason W.P., van den Bent M.J., et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med., 2005, vol.352(10), pp. 987-996. doi: 10.1056/NEJMoa043330

33. Rynda A.Yu., Olyushin V.E., Rostovtsev D.M., et al. Patients with long-term survival in malignant gliomas after photodynamic therapy. S.S. Korsakov Journal of Neurology and Psychiatry., 2024, vol.124(6), pp. 54-61. (In Russian). doi: 10.17116/jnevro202412406154