Abstract
BackgroundWhile the pace of commissioning of new charged particle radiation therapy facilities is accelerating worldwide, biological data pertaining to chordomas, theoretically and clinically optimally suited targets for particle radiotherapy, are still lacking. In spite of the numerous clinical reports of successful treatment of these malignancies with this modality, the characterization of this malignancy remains hampered by its characteristic slow cell growth, particularly in vitro.MethodsCellular lethality of U-CH1-N cells in response to different qualities of radiation was compared with immediate plating after radiation or as previously reported using the multilayered OptiCell™ system. The OptiCell™ system was used to evaluate cellular lethality over a broad dose-depth deposition range of particle radiation to anatomically mimic the clinical setting. Cells were irradiated with either 290 MeV/n accelerated carbon ions or 70 MeV accelerated protons and photons and evaluated through colony formation assays at a single position or at each depth, depending on the system.ResultsThere was a cell killing of approximately 20–40% for all radiation qualities in the OptiCell™ system in which chordoma cells are herein described as more radiation sensitive than regular colony formation assay. The relative biological effectiveness values were, however, similar in both in vitro systems for any given radiation quality. Relative biological effectiveness values of proton was 0.89, of 13–20 keV/μm carbon ions was 0.85, of 20–30 keV/μm carbon ions was 1.27, and >30 keV/μm carbon ions was 1.69. Carbon-ions killed cells depending on both the dose and the LET, while protons depended on the dose alone in the condition of our study. This is the first report and characterization of a direct comparison between the effects of charged particle carbon ions versus protons for a chordoma cell line in vitro. Our results support a potentially superior therapeutic value of carbon particle irradiation in chordoma patients.ConclusionCarbon ion therapy may have an advantage for chordoma radiotherapy because of higher cell-killing effect with high LET doses from biological observation in this study.
Highlights
In cancer therapy, the main treatment modalities are, or include, surgery, chemotherapy and radiation therapy
Carbon ions were accelerated to 290 MeV/n using the Heavy Ion Medical Accelerator in Chiba (HIMAC) and protons were accelerated to 70 MeV using the NIRS930 cyclotron delivery port in C-8
Cell survival versus depth in water Cell survival assays were conducted with our stacked OptiCellTM cell culture system, and cells irradiated with carbon ion and proton particles
Summary
The main treatment modalities are, or include, surgery, chemotherapy and radiation therapy. Intensifying efforts have been invested in devising improved and novel radiation therapy treatments based on innovative technologies and devices [1]. Several recent clinical studies have reported that outcomes from charged particle beam radiation therapy yield equivalent or superior outcomes to surgical modalities in a number of cases such as prostate, lung, head and neck, bone and soft tissue tumors [4,5]. Namely chordomas, malignancies appear to be highly responsive to charged particle radiation therapy which maximally preserves adjacent organs and their function, whereas the latter are difficult to preserve through unavoidably highly invasive surgery [5,6,7,8,9]. In spite of the numerous clinical reports of successful treatment of these malignancies with this modality, the characterization of this malignancy remains hampered by its characteristic slow cell growth, in vitro
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