Evaluation of the influence of fluorescence surgery in patients with glioblastoma on long-term treatment results

Introduction. Glioblastoma is the most aggressive primary brain tumor, characterized by rapid progression and a median survival of no more than 12–18 months. Fluorescence-guided surgery should be of critical importance, as it allows visualization of the tumor and facilitates its complete removal, which is essential for increasing survival. Purpose of the study. Comparative analysis of remote treatment results in patients with glioblastoma using fluorescent surgery and white light surgery without fluorophores. Material and methods. A single-center, retrospective study included 54 patients with newly diagnosed glioblastoma (24 patients in the main group with fluorescent surgery; 30 patients in the control group with white light surgery without fluorophores). In the main group, 11 patients used 5 ALA (20 mg/kg) orally, and 13 patients received Photoditazine (1 mg/kg) intravenously. Preoperative magnetic resonance imaging (MRI) data allowed complete resection of contrast-positive tumor areas, according to the operating surgeon, in all patients. The groups were representative in terms of gender, age, tumor size, preoperative Karnofsky index, tumor resection radicality, and volume of postoperative adjuvant therapy. All patients underwent surgery using an operating microscope. Control of resection radicality was assessed based on contrast-enhanced MRI data performed within 24 hours after surgery. Remote treatment results were assessed based on overall and relapse-free survival data, taking into account stratification by MGMT promoter status as a predictive biomarker of response to adjuvant therapy. Results. The GTR97 % index in the fluorescent surgery group was 91.70 %, while in the control group it was only 60 %. The median free-progression survival in the fluorescence-guided surgery group was 10.1±1.1 months, in the control group (with white light surgery, without fluorescence-guided surgery) was 6.3±1.3 months (p=0.049). The median overall survival in the fluorescence-guided surgery group was 19.2±1.5 months, in the control group (with white light surgery, without fluorescence-guided surgery) was 13.6±1.4 months (p=0.075). The MGMT promoter status in patients was the main predictive independent prognostic factor (p>0.05), influencing the median overall and recurrence-free survival in both groups. The median overall survival in patients with a methylated MGMT promoter (MGMT+) in the fluorescent surgery group was 25.3±1.3 months, in the control group (with white light surgery, without fluorescent surgery) 16.8±1.1 months (p=0.068). For patients with an unmethylated MGMT promoter (MGMT-), the median overall survival in the fluorescent surgery group was 17.1±1.4 months, in the control group 11.0±1.9 months (p=0.083). Conclusion. Fluorescence-guided surgery not only increases the radicality of the surgical intervention, ensuring more accurate detection of the tumor and its resection, but also increases the median overall and relapse-free survival in patients with glioblastoma.

1. Ostrom QT, 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-Oncology. 2021;23:III1–III105. https://doi.org/10.1093/NEUONC/NOAB200

2. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro Oncology. 2021;23:1231–1251. https://doi.org/10.1093/neuonc/noab106

3. Goryaynov SA, Okhlopkov VA, Golbin DA, et al. Fluorescence diagnosis in neurooncology: retrospective analysis of 653 cases. Front Oncol. 2019;6(9):830. https://doi.org/10.3389/fonc.2019.00830

4. Rynda AYu, Olyushin VE, Rostovtsev DM, et al. Intraoperative photodynamic therapy in complex treatment of malignant gliomas. Burdenko’s Journal of Neurosurgery. 2023;87(1):25–34. (In Russ.) https://doi.org/10.17116/neiro20238701125

5. Nguyen TTT, Mnatsakanyan H, Yi E, Badr CE. Current and emerging fluorescence-guided techniques in glioma to enhance resection. Cancers. 2025;17(16):2702. https://doi.org/10.3390/cancers17162702

6. Rynda AY, Olyushin VE, Rostovtsev DM, et al. Minimally invasive surgical treatment of glioblastomas using interstitial photodynamic therapy. Malignant Tumors. 2025;15(1):35–49. (In Russ.) https://doi.org/10.18027/2224-5057-2025-044

7. Mazurek M, Lehman N, Stoma F, et al. How 5-ALA enlightens neurosurgery — Results of a single centre study on highgrade gliomas. Ann Agric Environ Med. 2025;32:133–141. https:// doi.org/10.26444/aaem/194075

8. Rynda AYu, Olyushin VE, Rostovtsev DM, et al. Results of microsurgical resection of glioblastomas under endoscopic and fluorescent control. Biomedical Photonics. 2024;13(3):20–30. (In Russ.) https://doi.org/10.24931/2413-9432-2024-13-3-20-30

9. Olyushin VE, Kukanov KK, Nechaeva AS, et al. Photodynamic therapy in neurooncology. Biomedical Photonics. 2023;12(3):25– 35. (In Russ.) https://doi.org/10.24931/2413-9432-2023-12-3-25-35

10. Stummer W, Muther M, Spille D. Beyond fluorescenceguided resection: 5-ALA-based glioblastoma therapies. Acta Neurochir. 2024;166:163. https://doi.org/10.1007/s00701024-06049-3

11. Palmieri G, Cofano F, Salvati LF, et al. Fluorescence-guided surgery for high-grade gliomas: state of the art and new perspectives. Technol Cancer Res Treat. 2021;20:15330338211021604. https://doi.org/10.1177/15330338211021605

12. Rynda AYu, Olyushin VE, Rostovtsev DM, et al. Patients with long-term survival in malignant gliomas after photodynamic therapy. SS Korsakov Journal of Neurology and Psychiatry. 2024;124(6):54–61. (In Russ.) https://doi.org/10.17116/jnevro202412406154

13. Wang C, Yu Y, Wang Y, et al. Utility and safety of 5-ala guided surgery in pediatric brain tumors: a systematic review. Cancers. 2024;16:3677. https://doi.org/10.3390/cancers16213677

14. Ahmed N, Hossain MN, Ahmed R, et al. Safety, efficacy, and side effects of sodium fluorescein-aided resection of glioblastoma: A quasi-experimental study. Ann Med Surg. 2024;86:6521– 6530. https://doi.org/10.1097/MS9.0000000000002633

15. Rynda AYu, Olyushin VE, Rostovtsev DM, Zabrodskaya YuM, Papayan GV. Comparative analysis of 5-ALA and chlorin E6 fluorescenceguided navigation in malignant glioma surgery. Pirogov Russian Journal of Surgery. 2022;(1):5–14. (In Russ.) https://doi.org/10.17116/hirurgia20220115

16. Chirizzi C, Pellegatta S, Gori A, et al. Next-generation agents for fluorescence-guided glioblastoma surgery. Bioeng Transl Med. 2024;9:e10608. https://doi.org/10.1002/btm2.10608

17. Rynda AYu, Zabrodskaya YuM, Olyushin VE, et al. Morphological evaluation of the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas. Russian Journal of Archive of Pathology. 2021;83(5):13–20. (In Russ.) https://doi.org/10.17116/patol20218305113

18. Picart T, Pallud J, Berthiller J, et al. Use of 5-ALA fluorescenceguided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): A French multicenter randomized phase III study. J. Neurosurg. 2024;140:987–1000. https://doi.org/10.3171/2023.7.JNS231170

19. Rynda AYu, Olyushin VE, Rostovtsev DM, et al. Fluorescent diagnostics with chlorin e6 in surgery of low-grade glioma. Biomedical Photonics. 2021;10(4):35–43. (In Russ.) https://doi.org/10.24931/2413-9432-2021-10-4-35-43

20. Chen JS, Young JS, Berger MS. Current and future applications of 5-aminolevulinic acid in neurosurgical oncology. Cancers. 2025;17:1332. https://doi.org/10.3390/cancers17081332

21. Rynda AYu, Rostovtsev DM, Olyushin VE, Zabrodskaya YuM. Fluorescence-guided resection of glioma using “photoditazin”. Grekov’s Bulletin of Surgery. 2017;176(5):10–15. (In Russ.) https://doi.org/10.24884/0042-4625-2017-176-5-10-15

22. Gautheron A, Bernstock JD, Picart T, et al. 5-ALA induced PpIX fluorescence spectroscopy in neurosurgery: A review. Front Neurosci. 2024;18:1310282. https://doi.org/10.3389/fnins.2024.1310282

23. Valerio JE, de Jesus Aguirre Vera G, Zumaeta J, et al. Comparative analysis of 5-ALA and fluorescent techniques in high-grade glioma treatment. Biomedicines. 2025;13:1161. https://doi.org/10.3390/biomedicines13051161

24. Xiao Y, Li M, Wang X, et al. Fluorescein-guided surgery in high-grade gliomas: Focusing on the eloquent and deep-seated areas. J Cancer Res Clin. Oncol. 2024;150:274. https://doi.org/10.1007/s00432-024-05796-1

25. Rynda AY, Rostovthev DM, Zabrodskaya YM, et al. Immunotherapy with autologous dendritic cells in the complex treatment of malignant gliomas — results. J Neurooncol. 2024;166:309–319. https://doi.org/10.1007/s11060-023-04559-1

26. Hu D, Zha M, Zheng H, et al. Recent advances in indocyanine green-based probes for second near-infrared fluorescence imaging and therapy. Research. 2025;8:0583. https://doi.org/10.34133/research.0583

27. Rynda AY, Olyushin VE, Rostovtsev DM, et al. Patients with long-term survival in malignant gliomas after photodynamic therapy. Neurosci Behav Physi. 2024;54:1215–1221. https://doi.org/10.1007/s11055-024-01717-4

28. Giuliani S, Paraboschi I, McNair A, et al. Monoclonal antibodies for targeted fluorescence-guided surgery: a review of applicability across multiple solid tumors. Cancers. 2024;16:1045. https://doi.org/10.3390/cancers16051045

29. Rynda AY, Olyushin V, Rostovtsev D. Immunotherapy with autological dendritic cells in the structure of complex treatment of gliomas. Neurosurgery. 2024;70(1):196. https://doi.org/10.1227/neu.0000000000002809_1244

30. Bailey D, Zacharia BE. Intraoperative imaging techniques to improve tumor detection in the surgical management of gliomas. Adv Cancer Res. 2025;166:103–135. https://doi.org/10.1016/bs.acr.2025.05.001

31. Elliot M, Segaud S, Lavrador JP, et al. Fluorescence guidance in glioma surgery: a narrative review of current evidence and the drive towards objective margin differentiation. Cancers. 2025;17:2019. https://doi.org/10.3390/cancers17122019

32. Rynda AY, Olyushin V, Rostovtsev D. Immunotherapy with autologous dendritic cells in the complex treatment of malignant gliomas — results. Neurosurgery. 2025;71(1):54. https://doi.org/10.1227/neu.0000000000003360_209

33. Nikova AS, Vlotinou P, Karelis L, et al. Gross total resection with fluorescence could lead to improved overall survival rates: a systematic review and meta-analysis. Br J Neurosurg. 2022;36:316–322. https://doi.org/10.1080/02688697.2021.1950637

34. Rynda A, Olyushin V, Rostovtsev D. Immunotherapy in the complex treatment of HGG. Neuro-Oncology. 2021;23(2):i47. https://doi.org/10.1093/neuonc/noab180.164

35. Olyushin V, Rynda A, Rostovtsev D. Immunotherapy with autologous dendritic cells as part of the complex treatment of patients with malignant gliomas. Annals of Oncology. 2020;31(4):S405. https://doi.org/10.1016/j.annonc.2020.08.493

36. Rynda AYu, Rostovtsev DM, Olyushin VE, et al. Therapeutic pathomorphosis in malignant glioma tissues after photodynamic therapy with сhlorin e6 (reports of two clinical cases). Biomedical Photonics. 2020;9(2):45–54. https://doi.org/10.24931/2413-9432-2020-9-2-45-54

37. Wong LS, St. George J, Agyemang K, et al. Outcomes of fluorescence-guided vs white light resection of glioblastoma in a single institution. Cureus. 2023;15:e42695. https://doi.org/10.7759/cureus.42695

38. Rynda AYu, Olyushin VE, Rostovtsev DM, et al. Intraoperative fluorescence control with chlorin E6 in resection of glial brain tumors. Zhurnal Voprosy Neirokhirurgii Imeni NN Burdenko. 2021;85(4):20–28. (In Russ.) https://doi.org/10.17116/neiro20218504120

39. Rynda AYu, Olyushin VE, Zabrodskaya YuM. Intraoperative stimulated combined scattering (SRS) microscopy in brain glioma surgery. A literature review. Russian Neurosurgical Journal named after professor AL Polenov. 2017;IX(3):64–73. (In Russ.)

40. Rodriguez B, Brown CS, Colan JA, et al. Fluorescenceguided surgery for gliomas: past, present, and future. Cancers. 2025;17(11):1837. https://doi.org/10.3390/cancers17111837

41. Palmieri G, Cofano F, Salvati LF, et al. Fluorescence-guided surgery for high-grade gliomas: state of the art and new perspectives. Technol Cancer Res Treat. 2021;20:15330338211021604. https://doi.org/10.1177/15330338211021605

42. Rynda AYu, Olyushin VE, Rostovtsev DM, et al. Possibilities of interstitial photodynamic therapy in the treatment of brain glioblastoma. Biomedical Photonics. 2025;14(1):4–19. (In Russ.) https://doi.org/10.24931/2413-9432-2025-14-1-4-19

43. Smith EJ, Gohil K, Thompson CM, et al. Fluoresceinguided resection of high grade gliomas: a meta-analysis. World Neurosurg. 2021;155:181–188.e7. https://doi.org/10.1016/j.wneu.2021.08.126

44. Rynda AYu, Rostovtsev DM, Olyushin VE. Fluorescenceguided resection of glioma — literature review. Russian Neurosurgical Journal named after professor AL Polenov. 2018; X (1):97–110. (In Russ.)

45. Ahrens LC, Krabbenhoft MG, Hansen RW, et al. Effect of 5-Aminolevulinic acid and sodium fluorescein on the extent of resection in high-grade gliomas and brain metastasis. Cancers. 2022;14:617. https://doi.org/10.3390/cancers14030617

46. Rynda A, Olyushin V, Rostovtsev D, Zabrodskaya Y. Influence of the expression of ABCG2 transporters on the results of photodynamic therapy in malignant gliomas. Annals of Oncology. 2021;32(5):S523. https://doi.org/10.1016/j.annonc.2021.08.026

47. Romeo E, Tzakos AG, Crook T, et al. Agents for fluorescenceguided glioblastoma surgery. Pharmaceutics. 2025; 17(5):637. https://doi.org/10.3390/pharmaceutics17050637

48. Rynda A, Olyushin V, Rostovtsev D, Zabrodskaya Y. Long-term survival following photodynamic therapy for malignant glioma depending on MGMT status. Annals of Oncology. 2020;31(4):S402. https://doi.org/10.1016/j.annonc.2020.08.486

49. Pepper NB, Eich HT, Müther M, et al. ALA-RDT in GBM: Protocol of the phase I/II dose escalation trial of radiodynamic therapy with 5-Aminolevulinic acid in patients with recurrent glioblastoma. Radiat Oncol. 2024;19:11. https://doi.org/10.1186/s13014-024-02408-7

50. Goryaynov SA, Buklina SB, Khapov IV, et al. 5-ALA-guided tumor resection during awake speech mapping in gliomas located in eloquent speech areas: Single-center experience. Front Oncol. 2022;12:940951. https://doi.org/10.3389/fonc.2022.940951

51. Picart T, Berhouma M, Dumot C, et al. Optimization of high-grade glioma resection using 5-ALA fluorescence-guided surgery: a literature review and practical recommendations from the neuro-oncology club of the French society of neurosurgery. Neurochirurgie. 2019;65(4):164–177. https://doi.org/10.1016/j.neuchi.2019.04.005