Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system in adults. Dismal survival rates and poor prognosis for recurrent GBM patients still remains a challenging problem. Despite aggressive initial treatment, above 100 % GBM patients have development of recurrent diseases. Management of GBM recurrence is still debatable. The multimodality approaches using combination of stereotactic radiosurgery (SRS), cytostatic agents (Тemozolomide (TMZ)) and antiangiogenic therapy (bevacizumab (BEV)) are often beneficial for such patients and may achieve survival improving. Aim of research: to assess the efficacy and toxicity of combination therapy approach using stereotactic radiosurgery (SRS) and systemic treatment (chemotherapy and antiangiogenic therapy) in glioblastoma multiforme recurrence treatment. Materials and methods: at the State Institution “Institute of Neurosurgery named after acad. A.P. Romodanov of NAMS of Ukraine” (Kyiv, Ukraine) 21 patients (pts) with GBM recurrence were treated (8 females and 11 men; median age at time of diagnosis 52.4 (29.7–69.3) from January 2014 till December 2017. The initial surgical treatment as gross total tumor resection was performed in 12 pts (57.1 %), subtotal resection – 5 pts (23.9 %), biopsy – 4 pts (19 %). 12 pts (57.1 %) were MGMT methylated and 9 pts (42.9 %) were MGMT unmethylated. In all cases adjuvant radiation therapy (60 Gy in 30 fractions) were used, 12 pts of them (57.1 %) – in combination with TMZ followed by 6-12 courses of chemotherapy (TMZ) according Stupp protocol. Recurrent disease was treated by SRS followed by TMZ + BEV. SRS was performed by means of “Trilogy” LINAC (“Varian”, USA) with a median dose and fractions of 19.2 Gy (range, 12.0–36.0) in 1 to 5 fractions. Results: median survival after initial diagnosis was 18.3 months, and 1- and 2-year survival rates of 85.7 % (18 from 21 pts) and 38.1 % (8 from 21 pts) respectively. The median survival from the time of recurrence treatment was 8.3 months. The 6‐ and 12‐months overall survival from SRS were 95.2 % (20 from 21 pts) and 23.8 % (5 from 21 pts), respectively. Adverse radiation effects were noted in 6 (28.6 %) pts and were controlled with corticosteroids. Adverse events grade 1-2 related to the systemic therapy included hematological complications, fatigue, hypertension and proteinuria were observed in 23.8 % (5 from 21 pts) without the occurrence of grade 3 events. Conclusion: recurrent GBM management using combination of SRS, chemotherapy and antiangiogenic therapy is a promising multimodal treatment approach providing survival improving whereas appropriate toxicity ratio. Further studies of combined treatment of GBM relapse are needed.
Background. In the modern world, the incidence of cancer diseases is rapidly increasing and is the second most common cause of death. This is preconditioned by the quantitative growth of the senior and elderly population, as well as the growth of the main risk factors for cancer, which is related to the socio-economic development of society. About half of cancer cases require radiation therapy (RT) as a component of multimodal treatment, therefore its improvement, namely the introduction of hypofractionated radiation regimens, is considered today as one of the most effective ways to increase availability of oncological care and optimize the use of health care system resources. Purpose. To find out clinical and medico-social advantages of the hypofractionated approach in radiation oncology in order to optimize the functioning of the health care system by increasing availability of treatment for cancer patients. To highlight the importance of hypofractionated RT in terms of evidence-based medicine for the most common oncological pathology and in neuro-oncology. To demonstrate the influence of the COVID-19 pandemic on the implementation of hypofractionated RT. To present our own experience of using hypofractionated radiation regimens in patients with glioblastoma (GB). Materials and methods. MEDLINE (Pubmed), EMBASE (Ovid), Web of Science (Web of Knowledge) databases were used to search for literature. The search was performed in the English-language sources with the following keywords: «Radiation», «Hypofractionation radiotherapy», «Hypofractionated radiotherapy», «Hypofractionated irradiation»; «Breast cancer»; «Prostate cancer»; «Lung cancer»; «Glioblastoma», COVID-19. Systematic reviews, meta-analyses, randomized controlled trials and retrospective clinical trials were reviewed in full. The primary sources were backreferenced to identify additional relevant studies related to hypofractionated radiation treatment regimens. The last date of the search is 05.25.2023. The authors’ own experience of the hypofractionated approach in the adjuvant radiation treatment of patients with GB is presented briefly, as a reflection of the relevance of the authors’ practical experience to the provisions of the narrative review, based on the results of a retrospective single-center non-randomized study conducted at the State Institution «Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine» in 2014–2020. The oncological results of 110 (69.2%) patients of the hypofractionated RT group (15 fractions, single fraction dose (SFD) 3.5 Gy, total fraction dose (TFD) 52.5 Gy) and 49 (30.8%) patients of the standard RT group (30 fractions, RVD 2.0 Gy, SVD 60.0 Gy) were compared. RT was performed with Trilogy linear accelerator (USA) (6 MeV) using the intensity-modulated radiotherapy method (IMRT). Overall survival (OS) and recurrence-free survival (RFS) in the groups were analyzed. Results and discussion. Hypofractionated approaches, which allow to significantly decrease the duration of radiation treatment, have clinical, medical and social advantages, including: increased comfort for a patient; reduction of the workload on staff and technological equipment of medical facilities; reduction of the cost of treatment. The introduction of hypofractionated RT allows to increase access to cancer care at the global level, reducing disparity in the results of treatment of cancer patients between low- and middle-income countries and the countries with high income level. Hypofractionated radiation regimens are included in the clinical guidelines of professional associations, as for the most common forms of cancer and for malignant brain tumors, and represent the standard of treatment for particular clinical cases. Our experience of using the hypofractionated radiation regimen is based on the adjuvant radiation treatment of 110 patients with GB and in terms of clinical results is a relevant concept presented in a narrative review. The analysis showed no statistical difference between the groups of standard fractionation and hypofractionated RT in OS (Logrank test p = 0.06757) and RFS (Logrank test p = 0.43374). In the hypofractionation group, with an observation time median of 22.3 months, the OS median was 16.5 (95% CI 14.1–18.8) months; median RFS was 9.0 (95% CI 8.0–10.0) months. In the standard radiation regimen group, with a median of observation time of 24.4 months, the median OS was 15.0 (95% CI 14.1–17.1) months; median RFS is 9.0 (95% CI 9.0–10.0) months. Conclusion. Development and implementation of the measures designed to optimize the use of resources of medical facilities of Ukraine is a necessary condition for maintaining high-quality care for cancer patients in the conditions of full-scale military aggression, which has been ongoing since February 24, 2022. Increased application of hypofractionated approaches in radiation oncology can be considered as a potential tool for optimization of the use of resources of the healthcare system of Ukraine and enhancing public health.
Objective: to study the effect of antiangiogenic therapy on the quality of life and the level of headache in patients with recurrent glioblastoma who underwent radiosurgical treatment. Materials and methods. A prospective randomized single-center study carried out at the Romodanov Neurosurgery Institute of National Academy of Medical Sciences of Ukraine in 2019-2020 involving 45 patients with GB with clinical and radiological signs of disease progression and local tumor recurrence. In this regard, patients underwent radiosurgical treatment. In the main group (BEV+) 21 patients after stereotactic radiosurgery (SRS) underwent antiangiogenic therapy with Bevacizumab (BEV). In the control group (BEV–), 24 patients did not receive antiangiogenic therapy after SRS. SRS with the use of a linear accelerator «Trilogy» (6 MeV) using intensity-modulated radiotherapy (IMRT). BEV was administered intravenously, once every 3 weeks at a dose of 10 mg / kg body weight. Antiangiogenic therapy was performed under the condition of preserved liver and kidney function, values of full blood count and blood biochemistry within normal range. Global health status and headache levels were calculated according to EORTC QLQ-C30 v. 3.0 and QLQ-BN20 before and six weeks after radiosurgery in the main and control groups. Results. There was no a statistically significant difference between the studied groups of patients’ in quality of life (p = 0.707372) and in headache level (p = 0.846660) before the SRS. Six weeks after SRS, patients in the main group had a statistically significantly higher quality of life (p = 0.000015) and a lower level of headache than patients in the control group (p = 0.000035). During the observation period in patients of both groups there were no adverse events of III-IV degree of toxicity, in particular specific complications of antiangiogenic therapy (hypertension, bleeding, thromboembolism, leukopenia, proteinuria, gastrointestinal disorders, etc.). Conclusions. Antiangiogenic therapy statistically significantly improves the quality of life and reduces the level of headache in patients who underwent radiosurgical treatment for glioblastoma recurrence.
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