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子宮頸がん放射線治療における非剛体位置合わせを用いた危険臓器の有害事象予測に関する検討

宮坂 友侑也 東北大学

2021.03.25

概要

【目的】子宮頸がんに対する標準的な放射線治療では、体の外から放射線を照射する EBRT(external beam radiotherapy;外部照射)と子宮の中から放射線を照射するBT(brachytherapy;小線源治療)を組みあわせた治療が実施される。この一連の治療を通した OAR(organ at risk;危険臓器)の合算線量の算出は、 OAR の有害事象を予測するための重要な評価項目である。この合算線量の算出を、従来までは各治療計画の線量指標の値を算術的に足し算する方法 (従来法)で行っていたが、この方法で評価している線量は、高線量照射される領域が各治療において臓器の同一の場所で重なっていた場合の線量である。しかしながら、各治療における臓器は全く同じ位置ではなく、高線量域が毎回の治療時に同じ位置に重なるという保証はないため、従来法では OAR の線量が最も高くなる状況を評価することになり、OAR 線量を過大評価するという欠点がある。この解決策として 、DIR(deformable image registration;非剛体位置合わせ)を用いた OAR 合算線量評価法(新手法)が提案されている。DIR は画像変形を用いた位置合わせ技術であり、臓器形状の違う各治療の CT 画像を、目標とするある治療回の CT 画像と一致するように変形することにより、各治療の臓器変動を考慮した合算線量の評価が可能となる。しかしながら、現在まで新手法による合算線量と有害事象の相関関係については明らかになっていない。よって、本研究では、放射線治療を施行した子宮頸がん患者に実際に発生した腸管有害事象と、従来法と新手法のそれぞれで算出した合算線量の関係から、新手法の有効性を評価した。また、有害事象評価において誤差の要因となりえる、BT の治療中変動が、合算線量評価に影響を与える可能性があるかを評価した。

【方法】新手法の有害事象予測能力の評価のため、BT と EBRT を施行した子宮頸がん 59 症例を対象とした。全症例で従来法と、BT と EBRT の全線量を DIR により用いて合算した新手法 A、全 BT の線量を DIR で合算した後、全骨盤照射の線量を算術的に合算した新手法 B の三種類の方法で合算線量を算出した。直腸および S 状結腸の有害事象 grade1 以上が確認された有害事象あり群と、grade0 以下であった有害事象なし群の間で、各合算線量算出手法によって算出した線量指標(𝐷𝐷2𝑐𝑐𝑐𝑐3 、𝐷𝐷1𝑐𝑐𝑐𝑐3 、𝐷𝐷0.1𝑐𝑐𝑐𝑐3 、V50Gy、V60Gy、 V70Gy)を比較した。また、有害事象予測能力比較のために、各合算線量算出手法による線量指標の ROC 曲線から算出される AUC の値を比較した。次に、BT 治療中の直腸の線量変動を評価した。BT を施行された 15 症例に対して実施された 58 治療回のデータを解析した。治療計画 CT である治療前 CT と、BT 後直ちに取得した治療後 CT とをアプリケータが一致するように剛体位置合わせを実施した。剛体位置合わせに従い、BT 前 CT 上の予定線量を、治療後 CT へ割り付け、これを実線量とした。予定線量と実線量の比較により、直腸の治療中変動を評価した。

【結果】新手法の有害事象予測能力の評価について、𝐷𝐷2𝑐𝑐𝑐𝑐3 の有害事象ありとなしの群間の線量差は従来法、新手法 A、新手法 B でそれぞれ 0.2、5.7、3.1 Gy であり、新手法 A が最も大きな線量差を示した。また、𝐷𝐷2𝑐𝑐𝑐𝑐3 の AUCは従来法、新手法 A、新手法 B で、それぞれ 0.51、0.67、0.57 であり、新手法 A が最も高い値を示し、従来法に対する有意差が確認された。新手法 Aで算出した V60Gy と V70Gy の AUC は、それぞれ 0.63、0.65 であった。BT治療中変動に起因した直腸の𝐷𝐷2𝑐𝑐𝑐𝑐3 の線量変動について、各症例で解析した際の平均の変動は-2.3%であったが、最大の変動を示した症例では-13.3%の変動が確認された。

【結論】新手法は従来法に比較し、腸管有害事象の発生をより高精度に予測できる可能性があることが分かった。また、骨盤内へ照射されたすべての線量を、DIR を用いて合算するという方法により、より精度の高い有害事象予測が可能となることが示唆された。BT 治療中変動について、大きな変動を生じている症例が確認されたことから、治療中変動の低減、および適切な変動の考慮は有害事象予測能力のさらなる向上につながると考えられる。

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