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Limitations of current RBE models and their implication for clinical trial design
https://repo.qst.go.jp/records/75761
https://repo.qst.go.jp/records/75761110f26f1-d27c-43f9-a5c3-e1e0e67fdaf2
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-05-07 | |||||
| タイトル | ||||||
| タイトル | Limitations of current RBE models and their implication for clinical trial design | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Matsufuji, Naruhiro
× Matsufuji, Naruhiro× Matsufuji, Naruhiro |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Unlike conventional X-ray, changing radiation quality within irradiation field and resultant enhancing relative biological effectiveness (RBE) toward its range end makes ion-beam therapy advantageous in realizing intense clinical effect on the deep-seated target while sparing surrounding normal tissues. On another front, this changing RBE of the ion beam makes it indispensable to use an appropriate RBE model that bridges between the radiation quality as input and biological effectiveness as output for safe and efficient ion-beam therapy. In Japan, the first RBE model dedicated for carbon-ion radiotherapy (CIRT) was established in a pragmatic manner, i.e., dose distribution was at first designed from in-vitro cell survival response of a reference human salivary gland (HSG) cell as a verifiable biological endpoint, then it was scaled to meet clinical response for therapeutic purpose. Recently the model was updated by integrating the microdosimetric kinetic model (MKM) that realizes to estimate the biological effectiveness of any radiation accurately from its microdosimetric therefore measurable quantity while the indication of the RBE-weighted therapeutic dose has been inherited. At National Institute of Radiological Sciences (NIRS), clinical trials of CIRT have been conducted with the RBE model since 1994 for various solid tumors. More than 11,000 patients have been treated in the past 24 years, and the retrospective analysis of the derived clinical outcomes have revealed the appropriateness of the RBE model. At the same time, there is still certain room for future improvement in the ongoing RBE model especially for coming biologically adaptive therapy. Among possible biological factors, current model explicitly considers only the radiosensitivity of one HSG cells. The tumor-specific difference in response is treated just as the difference in optimum dose found in the dose-escalation clinical trials. In addition, heterogeneity of the tumor such as variation in O2 pressure or the existence of radioresistant stem cells are not considered yet. The response of surrounding normal tissues has been analyzed recently, however, further study is necessary to take them into consideration in the treatment planning. In the world, different approach has been adopted in European facilities. Local Effect Model (LEM), another biological model developed at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Germany, shows almost comparable performance with MKM as model itself, however, different biological endpoint and reference condition selected for therapeutic application results in different indication of the therapeutic RBE-weighted dose even though the same physical dose is delivered. The difference in RBE between the models needs careful translation of the therapeutic RBE-weighted dose from one to the other. For instance, in the international clinical trial for pancreatic cancer treatment CHIPHER (Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer), 57.6 Gy (RBE) will be prescribed in total for those to be treated in Japanese CIRT facilities while 59.4 Gy (RBE) will be given for those placed to European facilities to deliver the identical absorbed dose. Translation of the tolerance dose of organs-at-risk (OARs) between the models is further complex therefore not yet achieved, however, add further weight in international clinical trials ahead. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ESTRO38 | |||||
| 発表年月日 | ||||||
| 日付 | 2019-05-28 | |||||
| 日付タイプ | Issued | |||||
