Comparison of human chordoma cell-kill for 290 MeV/n carbon ions versus 70 MeV protons in vitro

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.

Validation of64Cu-ATSM damaging DNA via high-LET Auger electron emission

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Solution Radioactivated by Hadron Radiation Can Increase Sister Chromatid Exchanges

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Investigation of ectopic recurrent skull base and cervical chordomas: The Institut Curie's proton therapy center experience

“…Postoperative radiotherapy (RT) can reduce the risk of recurrence after surgery and prolong survival . Because of the relative radioresistance of tumor cells and the proximity of vital radiosensitive structures, heavy particles (ie, protons and carbon ions) with ballistic and/or biological advantages are recommended …”