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スキャニング陽子線治療における線量付与の空間・時間的構造が生物学的効果に及ぼす影響に関する研究

笠松, 幸生 北海道大学

2023.03.23

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スキャニング陽子線治療における線量付与の空間・時間的構造が生物学的効果に及ぼす影響に関する研究

笠松, 幸生

北海道大学. 博士(医理工学) 甲第15516号

2023-03-23

10.14943/doctoral.k15516

http://hdl.handle.net/2115/90075

theses (doctoral)

Koki_Kasamatsu.pdf

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Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP

学位論文

スキャニング陽子線治療における線量付与の空間・時間的構造が
生物学的効果に及ぼす影響に関する研究
(Studies on impact of spatial and temporal structure of the dose delivery
on biological effectiveness in scanning proton therapy)

2023 年 3 月



笠松




幸生



学位論文

スキャニング陽子線治療における線量付与の空間・時間的構造が
生物学的効果に及ぼす影響に関する研究
(Studies on impact of spatial and temporal structure of the dose delivery
on biological effectiveness in scanning proton therapy)

2023 年 3 月



笠松




幸生



目次
発表論文目録および学会発表目録 ............................................................................................. 1
第 1 章 緒言 ................................................................................................................................. 3
1.1 がんと放射線治療の概要 ................................................................................................ 3
1.2 陽子線の線エネルギー付与 ............................................................................................ 5
1.3 陽子線治療における生物効果 ........................................................................................ 7
1.4 細胞の損傷修復 .............................................................................................................. 10
1.5 散乱体照射法とスキャニング照射法 .......................................................................... 11
1.6 本研究の目的 .................................................................................................................. 13
1.7 本論文の構成と概要 ...................................................................................................... 14
略語表 ........................................................................................................................................... 16
第 2 章 生物物理モデルによる陽子線生物効果の推定 ......................................................... 17
2.1 Linear Quadratic モデル .................................................................................................... 17
2.2 LQ モデルに基づく RBE・生物線量の導出 .................................................................. 18
2.3 細胞実験から得られる LQ モデルのパラメータ......................................................... 19
2.4 種々の生物物理モデルにおける LQ パラメータの LET 依存性 ............................... 21
2.5 修復効果と Lea-Catcheside の G-factor .......................................................................... 25
第 3 章 修復効果の細胞固有パラメータ依存性 ..................................................................... 29
3.1 手法 .................................................................................................................................... 29
3.1.1 線量率構造モデル ..................................................................................................... 29
3.1.2 修復効果影響の評価のための RBEr の定義........................................................... 31
3.1.3 生物モデルパラメータ ............................................................................................. 31
3.1.4 治療計画: 水ファントム .......................................................................................... 33
3.1.5 治療計画: 患者プラン .............................................................................................. 34
3.2 結果 .................................................................................................................................... 35
3.2.1 水ファントム ............................................................................................................. 35
3.2.2 患者プラン ................................................................................................................. 38
3.3 考察 .................................................................................................................................... 43
第 4 章 スキャニング陽子線治療における線量率構造の影響評価 ..................................... 46
4.1 手法 .................................................................................................................................... 46
4.1.1 線量率構造モデル ..................................................................................................... 46
4.1.2 線量計算用パラメータセット ................................................................................. 50
4.1.3 治療計画: 水ファントム .......................................................................................... 50
4.1.4 治療計画: 患者プラン .............................................................................................. 51
4.1.5 評価指標 ..................................................................................................................... 52
4.2 結果 .................................................................................................................................... 52
4.2.1 水ファントム ............................................................................................................. 52
4.2.2 患者プラン ................................................................................................................. 55

4.3 考察 .................................................................................................................................... 59
4.3.1 結果に対する考察 ..................................................................................................... 59
4.3.2 今後に向けた考察 ..................................................................................................... 63
第 5 章 総括および結論 ............................................................................................................. 66
謝辞 ............................................................................................................................................... 69
引用文献 ....................................................................................................................................... 71

発表論文目録および学会発表目録
本研究の一部は以下の論文に発表した。
1.

Koki Kasamatsu, Taeko Matsuura, Sodai Tanaka, Seishin Takao, Naoki Miyamoto, Jin-Min
Nam, Hiroki Shirato, Shinichi Shimizu, Kikuo Umegaki
“The impact of dose delivery time on biological effectiveness in proton irradiation with
various biological parameters”
Medical Physics, 47, 4644-4655, (2020)

2.

Koki Kasamatsu, Sodai Tanaka, Koichi Miyazaki, Seishin Takao, Naoki Miyamoto, Shusuke
Hirayama, Kentaro Nishioka, Takayuki Hashimoto, Hidefumi Aoyama, Kikuo Umegaki,
Taeko Matsuura
“Impact of a spatially dependent dose delivery time structure on the biological effectiveness
of scanning proton therapy”
Medical Physics, 49, 702-713, (2022)

本研究の一部は以下の学会に発表した。
1.

Koki Kasamatsu, Hiroki Shirato, Taeko Matsuura
“SLD repair impact on prolonged proton irradiation with various biological parameters”
The 7th GI-CoRE Medical Science and Engineering Symposium, 2019/8/18, Hokkaido
University Sapporo campus

2.

Koki Kasamatsu, Taeko Matsuura, Seishin Takao, Sodai Tanaka, Naoki Miyamoto, Jin-Min
Nam, Hiroki Shirato, Kikuo Umegaki
“SLD repair impact on prolonged proton irradiation with various cell specific parameters”
第 119 回日本医学物理学会学術大会, 2020 年 5-6 月, オンライン

3.

Koki Kasamatsu, Taeko Matsuura, Sodai Tanaka, Kikuo Umegaki
“SLD repair impact on treatment effectiveness of proton therapy with various cell specific
parameters”
2020 Joint American Association of Physicist in Medicine (AAPM)|Canadian Organization of
Medical Physicist (COMP) Virtual Meeting, 2020/7, virtual

4.

Koki Kasamatsu, Hikaru Hosoi, Sodai Tanaka, Koichi Miyazaki, Seishin Takao, Naoki
Miyamoto, Kikuo Umegaki, Shinichi Shimizu, Taeko Matsuura
“Inclusion of energy layer structure into an evaluation of dose delivery time effect in scanning
1

proton therapy”
第 121 回日本医学物理学会学術大会, 2021 年 4 月, 神奈川県パシフィコ横浜
5.

Koki Kasamatsu, Hikaru Hosoi, Sodai Tanaka, Koichi Miyazaki, Seishin Takao, Naoki
Miyamoto, Kikuo Umegaki, Takayuki Hashimoto, Kentaro Nishioka, Shinichi Shimizu,
Taeko Matsuura
“Influence of sub-lethal damage repair on biological effectiveness of proton with the
consideration of dose delivery time structure in scanning proton therapy”
American Association of Physicist in Medicine (AAPM) 63rd Annual Meeting, 2021/7/25-29,
virtual

2

第1章

緒言

1.1 がんと放射線治療の概要
がんは依然として我が国における死因の割合の最上位を占める疾患である。国立がん
研究センターがん情報サービスによれば、日本国内における 2020 年のがん死亡者数は
37 万人を超えており、年ごとに増加を続けている(図 1.1, 国立がん研究センターがん情
報サービス「がん統計」
(厚生労働省人口動態統計))。主な要因は高齢化とされている。
がんの克服と地域に関わらずに適切な医療を行うことを目指して 2006 年に成立したが
ん対策基本法(厚生労働省 HP)は 2016 年に改正され、改正がん対策基本法(厚生労働省
HP)としてより患者の生活の質(QOL; Quality of life)を意識したがん対策戦略の基盤とな
っている。国内の高齢化が進む中、こうした施策を受けてより効果的ながん治療の開発
が望まれている。

図 1.1 日本におけるがん死亡者数の年次推移(国立がん研究センターがん情報サービス
「がん統計」(厚生労働省人口動態統計)のデータをもとに作成)

がんに対する三大治療法として、外科治療、化学療法、そして放射線治療が広く知ら
れている。近年では第 4 の治療法になる可能性として免疫を利用した治療法や、これら
を組み合わせた集学的治療が研究されている。外科治療はがんの病巣自体を物理的に切
3

除する手法であり、多くのがんで効果が示されている。一方その侵襲性の高さから、体
力の衰えのある高齢者に対してはときに適応しづらいこともある。化学療法は抗がん剤
治療とも呼ばれ、薬剤によってがんを制御しようとするものである。外科手術のような
侵襲性は無いが、種類によっては副作用が大きいものもある。放射線治療は本論文の主
題であり、DNA(deoxyribonucleic acid)を損傷させることによってがん細胞の増殖能を無
くし、治癒に導く治療法である。放射線治療は非侵襲的で QOL の高い治療法であり、高
齢化の進む現代で注目されている。デメリットとなるのは放射線による正常臓器への副
作用であり、低減のための技術開発・研究が行われている。
現在、世界的に行われている放射線治療の多くを占めるのは X 線によるものである。
X 線は非荷電粒子線に分類され、物質との相互作用のうち主に、光電効果、コンプトン
散乱、電子陽電子対生成によって物質中にエネルギーを付与する。X 線はビルドアップ
部分を除いて物質中を進むにつれてその強度を落としていくという特徴を持っている。
非荷電粒子による治療法として、他に中性子線による治療法がある。中性子線は X 線と
同じような線量分布を示す一方で、酸素欠乏状態の細胞に対して、X 線に比べて高い治
療効果を示すことから盛んに研究がなされ、実際に治療も行われた (Podgorsak, 2015)。
現在では中性子線を直接利用するのではなく、人体に投与したホウ素薬剤と中性子線の
相互作用で発生するリチウム線によって腫瘍を狙い撃つホウ素中性子補足療法(BNCT;
Boron neutron capture therapy)が研究されている。X 線以外に一般的なものとして電子線
を使った治療法が挙げられる。電子線は X 線に比べて浅部で高い線量を付与する特徴を
持っており、例として皮膚がんの治療に用いられる。
浅部ではエネルギー付与が小さく、深部の一点で急激にエネルギー付与が増加すると
いう特徴を持つのが粒子線である。現在主に実用化されているのは陽子を使用する陽子
線と、炭素イオンを利用する炭素線である。この二つは X 線と異なり荷電粒子線に分類
される。粒子線治療ではサイクロトロンやシンクロトロンで加速された陽子、炭素イオ
ンを人体に照射することで治療を行う。陽子線の典型的な線量分布を図 1.2 に示す。陽
子線の急激な線量増加部分はブラッグピークと呼ばれている。このピークを重ね合わせ
て拡大ブラッグピーク(SOBP; Spread out Bragg-peak)を腫瘍形状に合わせて作成すること
で、X 線に比べて病巣に限局した照射が可能となる。SOBP の作成法は複数あり、それ
ぞれで散乱の影響などが異なる。 ...

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の推定. 東京工業大学大学院, 博士論文

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