Survival after stereotactic radiosurgery of recurrent glioblastomas in patients with radical resection of primary tumor
Authors: Griazov Andrii , Glavatskyi Oleksandr , Zemskova Oksana , Gryazov Andrey , Chuvashova Olga , Khmelnytskyi Hennadii , Shuba Iryna , Kruchok Iryna , Shevelov Maksim , Stuley Volodymyr 
Published: May 2022

glioblastoma (GBM) is an aggressive tumor with high rate of recurrence and estimated survival of 15-18 months after diagnosis. Factors associated with longer survival of GBM patients are age < 50 years, high performance status and radical resection of the primary tumor. The optimal treatment for recurrence/ progression of GBM has not yet been determined and remains a challenging issue. Stereotactic radiosurgery (SRS) is considered today as a therapeutic option for effective treatment of recurrent malignant gliomas. The aim of this retrospective study was to analyze the survival after SRS of the recurrent GBM in a cohort of 59 patients, which had a radical resection of the primary tumor. The cohort consisted of 59 patients (28 / 47.5% of women and 31 / 52.5% of men); the average age was 51 years (interval 24 - 81). SRS was performed by means of linear accelerator "Trilogy" (USA) (6 MeV) from 2014 to 2020 at the State Institution "Romodanov Neurosurgery Institute". In all cases, the diagnosis of grade 4 GBM according to the WHO classification was confirmed after neurosurgical procedures of the primary tumor. All 59 patients underwent the maximal safe removal of the primary tumor: in the vast majority of cases (54 / 91.5%) - in the perifocal area; in 5 / 8.5% of cases - subtotal. In all 59 cases, patients received adjuvant radiation therapy (total dose 60 Gy in 30 fractions); in 33 / 55.9% of cases radiotherapy was combined with concomitant alkylating chemotherapy (CHT) (Temozolomide 75 mg / m2). In 31 / 52.5% of patients, maintenance alkylating CHT was continued (Temozolomide 150-200 mg / m2). In most cases (51 / 86.4%) recurrent GBM (RGBM) was diagnosed by clinical and radiological signs; in 8 / 13.6% of patients - after repeated surgery. Overall survival (OS), recurrence/progression free survival (RFS) and survival after recurrence (SAR) represented the end-points of the study. The effect of the following quantitative and categorical factors (covariates) on the survival was studied: sex, age, performance status, combination of adjuvant RT with alkylating chemotherapy, neurosurgical procedures of RGBM, type of GBM recurrence, total dose of irradiation (BED11) and SRS dose (BED11), number of SRS fractions, volume of target in SRS, duration of RFS. The effect of RFS was studied in three independent groups: group I – RFS < 10 months; group II – RFS from 10 to 20 months; group III – RFS > 20 months. The survival was analyzed by Kaplan-Meier (KM) method. Log-rank test was used for analysis of the survival according to the binary predictors. The effect of several categorical factors on survival was analyzed by Pearson Chi-square test. The effect of the quantitative covariates on survival was studied by regression analysis in Cox proportional risk model. Hazard ratio was calculated with 95 % confidential intervals (CI). The analysis revealed the following. Median OS following SRS RGBM was 26.3 months (95 % CІ 17 – 45.5), median RFS was 12.9 months (95 % CІ 8.4 – 25.6), median SAR – 9.8 months (95 % CІ 6.7 – 24.4). Two-year OS in our study was 56 %. 6-month survival after SRS –77 %; one-year survival after SRS – 39 %, and two-year survival after SRS – 28 %. The significant impact of performance status (p = 0.00159), duration of recurrence-free period (p = 0.02711) and surgical resection of RGBM (р = 0.009391) on the OS was demonstrated. The best OS was shown for the patients with Karnofsky score 90, recurrence occurring after more than 20 months and previous surgical resection of RGBM. The effects of other factors on OS were not demonstrated. Such factors as age, sex, performance status, adjuvant RT with сoncomitant alkylating CHT, surgical resection of RGBM, type of recurrence, number of SRS fractions, BED11 in SRS RGBM, BED11 for overall courses of irradiation, SRS target volume demonstrated no effect on SAR. SRS is non-invasive method for RGBM treatment that allows for improving the survival without significant radiation toxicity. Primary biological properties of the tumor seem to be of priority in determining the survival of RGBM patients. Although irradiation of GBM is advantageous regarding the improvement of the survival, one could also speculate that re-irradiation of the recurrent malignant glioma triggers some changes in its biology neutralizing the potential effect of the survival factors that had predictive value before re-irradiation.