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A theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy
| Title: | A theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy |
| Authors: | Matsuya, Yusuke Browse this author →KAKEN DB | | Sato, Tatsuhiko Browse this author →KAKEN DB | | Nakamura, Rui Browse this author | | Naijo, Shingo Browse this author | | Date, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | hypoxia | | oxygen enhancement ratio (OER) | | cell-killing model | | DNA damage | | cell survival | | biological effective dose (BED) | | Markov chain Monte Carlo (MCMC) simulation |
| Issue Date: | 27-Apr-2020 |
| Publisher: | IOP Publishing |
| Journal Title: | Physics in medicine and biology |
| Volume: | 65 |
| Issue: | 9 |
| Start Page: | 095006 |
| Publisher DOI: | 10.1088/1361-6560/ab7d14 |
| PMID: | 32135526 |
| Abstract: | Radio-resistance induced under low oxygen pressure plays an important role in malignant progression in fractionated radiotherapy. For the general approach to predict cell killing under hypoxia, cell-killing models (e.g. the Linear-Quadratic model) have to be fitted to in vitro experimental survival data for both normoxia and hypoxia to obtain the oxygen enhancement ratio (OER). In such a case, model parameters for every oxygen condition needs to be considered by model-fitting approaches. This is inefficient for fractionated irradiation planning. Here, we present an efficient model for fractionated radiotherapy the integrated microdosimetric-kinetic model including cell-cycle distribution and the OER at DNA double-strand break endpoint (OERDSB). The cell survival curves described by this model can reproduce the in vitro experimental survival data for both acute and chronic low oxygen concentrations. The OERDSB used for calculating cell survival agrees well with experimental DSB ratio of normoxia to hypoxia. The important parameters of the model are oxygen pressure and cell-cycle distribution, which enables us to predict cell survival probabilities under chronic hypoxia and chronic anoxia. This work provides biological effective dose (BED) under various oxygen conditions including its uncertainty, which can contribute to creating fractionated regimens for multi-fractionated radiotherapy. If the oxygen concentration in a tumor can be quantified by medical imaging, the present model will make it possible to estimate the cell-killing and BED under hypoxia in more realistic intravital situations. |
| Rights: | This is an author-created, un-copyedited version of an article published in Physics in Medicine and Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.1088/1361-6560/ab7d14. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/81071 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 伊達 広行
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