Abstract
Carbon ion radiotherapy holds great promise for cancer therapy. Clinical data show that carbon ion radiotherapy is an effective treatment for tumors that are resistant to X-ray radiotherapy. Since 1994 in Japan, the National Institute of Radiological Sciences has been heading the development of carbon ion radiotherapy using the Heavy Ion Medical Accelerator in Chiba. The Gunma University Heavy Ion Medical Center (GHMC) was established in the year 2006 as a proof-of-principle institute for carbon ion radiotherapy with a view to facilitating the worldwide spread of compact accelerator systems. Along with the management of more than 1900 cancer patients to date, GHMC engages in translational research to improve the treatment efficacy of carbon ion radiotherapy. Research aimed at guiding patient selection is of utmost importance for making the most of carbon ion radiotherapy, which is an extremely limited medical resource. Intratumoral oxygen levels, radiation-induced cellular apoptosis, the capacity to repair DNA double-strand breaks, and the mutational status of tumor protein p53 and epidermal growth factor receptor genes are all associated with X-ray sensitivity. Assays for these factors are useful in the identification of X-ray-resistant tumors for which carbon ion radiotherapy would be beneficial. Research aimed at optimizing treatments based on carbon ion radiotherapy is also important. This includes assessment of dose fractionation, normal tissue toxicity, tumor cell motility, and bystander effects. Furthermore, the efficacy of carbon ion radiotherapy will likely be enhanced by research into combined treatment with other modalities such as chemotherapy. Several clinically available chemotherapeutic drugs (carboplatin, paclitaxel, and etoposide) and drugs at the developmental stage (Wee-1 and heat shock protein 90 inhibitors) show a sensitizing effect on tumor cells treated with carbon ions. Additionally, the efficacy of carbon ion radiotherapy can be improved by combining it with cancer immunotherapy. Clinical validation of preclinical findings is necessary to further improve the treatment efficacy of carbon ion radiotherapy.
Highlights
Carbon ion radiotherapy holds great promise for cancer therapy
Carbon ion radiotherapy showed good antitumor effects in patients with locally advanced uterine cervical cancer, irrespective of pretreatment intratumoral pO2 levels. These data indicate that assays to determine pretreatment intratumoral pO2 values will be useful for identification of X-ray-resistant tumors profiting from carbon ion radiotherapy
Complex carbon ion-induced double-strand breaks (DSBs) are more difficult to repair than X-ray-induced DSBs; these persistent unrepaired DSBs lead to mitotic catastrophe [16]. These data indicate that tumors with a high capacity for DSB repair are suitable for carbon ion radiotherapy
Summary
Carbon ion radiotherapy holds great promise for cancer therapy. Carbon ions have two advantages over X-rays such as a sharp dose distribution and a strong cell-killing capacity [1]. For many types of cancer, the SF2 value, i.e., the surviving fraction of X-irradiated tumor cells (irradiated ex vivo with a dose of 2 Gy) measured in a clonogenic survival assay, correlates with clinical outcome of X-ray radiotherapy [9]. These data indicate that assays to determine pretreatment intratumoral pO2 values will be useful for identification of X-ray-resistant tumors profiting from carbon ion radiotherapy.
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