Experimental Oncology ��� �������� ���� ��ecem�er� ��� �������� ���� ��ecem�er� ��ecem�er� ��� RADIOSURGICAL TREATMENT OF RECURRENT GLIOBLASTOMA AND PROGNOSTIC FACTORS AFFECTING TREATMENT OUTCOMES O.Ya. Glavatskyi 1 , A.B Griazov 1 , O.Yu. Chuvashova 1 , I.V. Kruchok 1 , A.A. Griazov 1 , H.V. Khmelnytskyi 1 , I.M. Shuba 1 , V.A. Stuley 2 , O.V. Zemskova 1, * 1 State Institution “Academician Romodanov Institute of Neurosurgery, the National Academy of Medical Sciences of Ukraine”, Kyiv 04050, Ukraine 2 Institute for Applied System Analysis NTUU “Igor Sikorsky Kyiv Polytechnic Institute”, Kyiv 03056, Ukraine Background: Glioblastoma (GBM) is the most prevalent malignant tumor of the brain in adults with the inherent aggressive be- havior and high recurrence rate. The stereotactic radiosurgery (SRS) is currently considered as one of the effective modalities for GBM treatment allowing for the improvement of survival with the acceptable toxicity level. Aim: To assess the effects of various factors on the survival of GBM patients following SRS. Patients and Methods: We retrospectively reviewed treatment outcomes of 68 patients who received SRS for recurrent GBM treatment in 2014–2020. SRS was delivered with Trilogy linear accelerator (6 MeV). The area of recurrent tumor/continued tumor growth was irradiated. For the treatment of the primary GBM, the ad- juvant radiotherapy was provided at the standard fractionated regimen with the total boost dose of 60 Gy divided to 30 fractions (Stupp’s protocol) in the setting of the concomitant chemotherapy with temozolomide. 36 patients then received temozolomide as the maintenance chemotherapy. SRS for the treatment of recurrent GBM was provided at a boost dose of 20.2 Gy on average being delivered into 1–5 fractions with average single dose of 12.4 Gy. The survival was analyzed by the Kaplan—Meier method with a log-rank test used for assessing the impact of the independent predictors on the survival risks. Results: The median overall survival (OS) was 21.7 months (95% confidence interval (CІ) 16.4–43.1), median survival after SRS was 9.3 months (95% CІ 5.6–22.7). The majority of patients (72%) were alive for at least 6 months following SRS and about half of patients (48%) survived for at least 24 months following the resection of the primary tumor. OS and survival after SRS depend significantly on the extent of the surgi- cal resection of the primary tumor. The addition of temozolomide to radiotherapy prolongs survival in GBM patients. The relapse time affected significantly OS (p = 0.00008), but not survival after SRS. Neither OS, nor survival after SRS were affected sig- nificantly by such factors as the age of patients, the number of SRS fractions (one fraction vs several fractions), and target volume. Conclusion: Radiosurgery improves the survival in patients with recurrent GBM. The extent of the surgical resection and adjuvant alkylating chemotherapy of the primary tumor, overall biologically effective dose and time between the primary diagnosis and SRS affect significantly the survival. The search for the more effective schedules for treating such patients requires further studies with more numerous cohorts of patients and extended follow-up. Key Words: malignant glioma, glioblastoma, neurosurgical procedures, recurrence, radiosurgery, survival. DOI: 10.32471/exp-oncology.2312-8852.vol-44-no-4.18920 Glio�lastoma �GBM� �glioma of the malignancy grade � �y the WHO classification� ranks first �y its inci- dence among the primary tumors of CNS in adults [�� �]. In spite of the thorough studies� the pathophysi- ological mechanisms of GBM have not yet �een elucidated in detail. The effective methods for GBM treatments are lacking� and the appropriate com�ina- tion of surgery� radiotherapy and chemotherapy �CTX� still fails to produce satisfactory outcomes. The mean overall survival of GBM patients is a�out �5 months [�]. The unfavora�le forecast in GBM is associated mostly with the inherent aggressive �ehavior of this cancer manifested in tremendously high recurrence rate �a�out 9�%� [�]. The current treatment of the pri- mary GBM is standardized and �ased on the criteria of evidence-�ased medicine. The treatment comprises the maximum safe resection of the tumor� adjuvant radiotherapy in the setting of the concomitant CTX with temozolomide followed �y the maintenance temozolo- mide CTX. Contrary to primary GBM� the standards for the treatment of recurrent GBM have not �een defined. The treatment strategy for GBM patients is considered �ased on the previous treatment modalities taking into account the age� Karnofsky performance status� the methylation status of MGMT� and the progres- sion of the disease [5]. The stereotactic radiosurgery �SRS� is currently considered as one of the effec- tive options for GBM treatment that could �e used as a component of the multimodal treatment or a single modality. The modern precision SRS techniques al- low the spatially precise targeted delivery of radiation dose sparing the adjacent areas of intact �rain tissue that is of particular importance for repeated irra- diation in cases of the local progression of malignant glioma [6�8]. Nevertheless� the num�er of systematic reviews and meta-analyses as well as clinical studies related to the radiosurgery of GBM is rather scarce. We attempted to assess the effects of various factors on the survival of GBM patients following SRS �ased on the analysis of our experience in the treatment of such a category of patients. Submitted: September 16, 2021. *Correspondence: Е-mail: oxzemskova@gmail.com Abbreviations used: BED — biologically effective dose; CІ — confi- dence interval; CTX — chemotherapy; GBM — glioblastoma; IDH — isocitrate dehydrogenase; MRI — magnetic resonance imaging; OS — overall survival; PTV — planning tumor volume; SRS — ste- reotactic radiosurgery. Exp Oncol ���� ��� �� �������