Title: Review of recent improvements in carbon ion radiotherapy in the treatment of glioblastoma
Abstract: Glioma represents the predominant form of neoplastic growth in the brain, accounting for approximately 51% of all malignancies affecting the nervous system. Currently, high-grade glioma, specifically glioblastoma, comprises 15% of cases and is associated with a high mortality rate. The development of novel drugs for the treatment of high-grade tumors has been impeded by various factors, such as the blood-brain barrier and tumor heterogeneity, despite numerous endeavors. According to the definition of tumor grade established by the World Health Organization (WHO), the conventional treatment involves surgical resection followed by adjuvant radiation and chemotherapy. Despite numerous attempts in photon radiation therapy to apply the highest possible dose to the tumor site while minimizing damage to healthy tissue, there has been no success in increasing patient survival. The primary cause of resistance to conventional radiotherapy methods, namely x-ray and gamma-ray, is attributed to the survival of radio-resistant glioma stem cells (GSCs), which have the potential to trigger a recurrence of tumors.Particle beams, such as protons and carbon ions, have the ability to deposit the highest dose to a confined region, thus offering a more accurate dose distribution compared to photon beams. Carbon ions exhibit higher linear energy transfer (LET) and relative biological effectiveness (RBE) compared to photons, potentially enabling them to overcome radio-resistant tumor cells. Therefore, it can be hypothesized that carbon ion radiotherapy (CIRT) may show superior efficacy in destroying neoplastic cells with reduced negative outcomes compared to X-ray radiotherapy (XRT). This paper provides an overview of the physical and biological properties of carbon ions, followed by an examination of the latest clinical outcomes in patients with glioma who have received CIRT.