Aspects of hypofractionation in modern radiation oncology

Abstract

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.