Factors affecting the survival of patients with glioblastoma treated with standard and hypofractionated radiation regimens

Abstract

Background. Glioblastoma has the worst prognosis and is the most common primary tumor of the central nervous system (CNS) among adults. Since it is multimodal treatment that increases survival chances of patients with glioblastoma, the analysis of factors that affect survival is a necessary precondition for developing more effective therapeutic approaches for this cohort. Such analysis makes it possible to determine the subgroups of patients which demonstrate the biggest therapeutic benefit from certain types of multimodal treatment, thus leading to implementation of personalized neuro-oncological treatment. Purpose. To analyze factors affecting cancer-specific survival (CSS) of patients with glioblastoma in stratification of the cohort according to the regimen of adjuvant radiation therapy into groups of standard and hypofractionated treatment regimens. Materials and methods. The single-center non-randomized study is based on the analysis of the results of the cohort of 159 patients with primarily diagnosed glioblastoma that were treated over the period from 2014 to 2020 at the State Institution «Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine». According to the regimen of radiation therapy, the patients of the cohort (n=159) were stratified into two groups: standard regimen group – 49 (30.8%) patients (30 fractions, total radiation dose of 60.0 Gy) and hypofractionated regimen group – 110 (69.2%) patients (15 fractions, total radiation dose of 52.5 Gy). The survival of the patients was analyzed by the Kaplan–Meier method. The log-rank test was used for comparing Kaplan–Meier survival curves for different studied groups. For the purpose of studying impact of independent variables on the survival, we used regression analysis according to semiparametric proportional hazards model. Hazard ratio was calculated with 95% confidence intervals (CI). Results and discussion. The median CSS in the total cohort was 16.6 (95% CI 14.1–17.8 months) months in median follow-up time of 23.8 (95% CI 21.9–27.3) months. In standard regimen group, the median CSS was 15.7 (95% CI 14.1–17.8) months in median follow-up time of 24.4 (95% CI 23.1–25.3) months. In hypofractionated regimen group, the median CSS was 17.5 (95% CI 14.6–19.7) months in median follow-up time of 22.3 (95% CI 21.3 – 27.2) months. According to the logrank test (taking into consideration cautions about its use), no statistically significant difference in CSS of patients of both groups was determined р=0.07>0.05. For analysis of the impact of clinical factors (age, sex, radicality of the surgical treatment, chemotherapeutic treatment, functional status according to the Karnofsky scale) on the CSS of both groups, they were considered as the ones that may have different base hazard. Statistically significant impact of all studied covariates on the CSS was registered (p70 points, ceteris paribus. For male patients, the hazard of death is 1.7 times higher (р=0.016267; HR 1.7; 95% CI 1.1–2.5) than for female patients, ceteris paribus. Absence of chemotherapy in adjuvant treatment increases hazard of death by 2.37 times (HR 2.37; 95% CI 1.6–3.2), ceteris paribus. The hazard of death decreases, ceteris paribus, by 82% in chemotherapy with temozolomide and by 47% when the patient is younger than 60 years old (HR 0.53; 95% CI 0.4–0.8). Conclusions. This analysis is a stage of the study of differentiated treatment effect in groups of standard and hypofractionated regimens of radiation therapy in patients with glioblastoma. These data can be used for an in-depth subgroup analysis and serve as the basis for development of personalized approaches in treatment of neuro-oncological patients.