Differences in Linear Energy Transfer Affect Cell-killing and Radiosensitizing Effects of Spread-out Carbon-ion Beams

Abstract

Background/Aim: The cell-killing and radiosensitizing effects of carbon-ion (C-ion) beams with low linear energy transfer (LET) are underexplored. We aimed to demonstrate the cell-killing effects of 60 Co gamma rays and Cion beams at various LET values and the radiosensitizing effect of C-ion beams at various LET and cisplatin levels. Materials and Methods: Human uterine cervical cancer cells were irradiated with 60 Co gamma rays and C-ion beams at different levels of LET, with and without cisplatin treatment. Results: Low-LET C-ion beams had a superior cell-killing effect compared to 60 Co gamma rays. Survival curves under low-LET C-ion beams were more similar to that of 60 Co gamma rays than that of high-LET C-ion beams. Cisplatin significantly reduced cell survival after 1, 2, and 3 Gy C-ion beam irradiations at LET values of 13/30/70 keV/μm, 13/30 keV/μm, and 13 keV/μm, respectively. Conclusion: Low-LET C-ion beams combined with cisplatin have higher radiosensitizing effects than high-LET C-ion beams. Carbon-ion radiotherapy (C-ion RT) was initiated in 1994 to treat various cancer types, and favorable treatment outcomes have been reported (1-10). These outcomes are due to its localizing properties and more significant biological advantages than X-ray RT, including distal tail-off due to the Bragg peak, a sharp lateral penumbra, and higher relative biological effectiveness (RBE) due to high linear energy transfer (LET) in the Bragg peak (1, 11, 12). Additionally, C-ion beams with high LET have a superior cell-killing effect against radioresistant and hypoxic cells (13).

Preliminary result of combined treatment with scanning carbon-ion radiotherapy and image-guided brachytherapy for locally advanced cervical adenocarcinoma

“…In an in vitro study, Shiba et al. reported a difference in survival rate with varying LET in CIRT of HeLa cells in human cervical adenocarcinoma [ 40 ]. Furthermore, the passive and scanning methods may result in slight differences in LET due to the different methods of forming the dose distribution.…”

Combining Cisplatin with Different Radiation Qualities—Interpretation of Cytotoxic Effects In Vitro by Isobolographic Analysis

“…Additionally, the importance of different LET values on radiosensitizing effects with cisplatin has been investigated. Shiba et al found that low-LET carbon-ion irradiation in combination with cisplatin produced higher cytotoxic effects than high-LET carbon-ion irradiation in cervical cancer cells [34]. On the other hand, carbon ion irradiation combined with cisplatin showed superior potential to kill breast cancer cells with irreparable DNA damage [35].…”

In VitroCarbon Ion Beam and Gemcitabine Chemoradiation in a Mucoepidermoid Carcinoma Cell Line

“…C) G2/M phase cell distribution following treatment with 2.0 Gy carbon ion-beams with 0.5 μg/ml gemcitabine and 6.0 Gy photon beams with 0.5 μg/ml gemcitabine. cells and the chemotherapeutic agent cisplatin a dependence of radiosensitization on the linear energy transfer (LET) of carbon ion irradiation, showing an increase in radiosensitivity in the low LET range (18). This could be attributed to the ability of high-LET irradiation to overcome radioresistance.…”