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乳癌治療における化学療法に関連した癌治療関連心不全の早期診断法の検討

照井 洋輔 東北大学

2021.03.25

概要

【背景】本邦における乳癌罹患数は年々増加傾向だが、化学療法を含めた集学的治療の発展により予後の改善を認めている。乳癌患者の予後改善に伴い癌治療関連心不全の増加が問題となっており、癌治療関連心不全の予測・早期診断法の開発は喫緊の課題である。また心臓 MRI を用いた native T1 値は、非侵襲的に心筋組織の組織学的状態を評価可能であり、native T1 値の上昇は様々な心疾患の予後との関連も報告されている。したがって本研究は、心臓 MRI が癌治療関連心不全の予測・早期診断法において有用との仮説を立て検証を行った。

【方法】東北大学病院循環器内科(腫瘍循環器外来)を受診した化学療法を受ける予定の乳癌患者を前向きに登録し、化学療法開始前から心臓画像評価(心臓超音波検査や心臓 MRI 検査)およびバイオマーカー測定、12 誘導心電図による心機能評価を行った。さらに CART(classification and regression tree, 分類木および回帰木)解析を用いて、癌治療関連心不全発生と関連する因子及び cut-off 値を決定し,癌治療関連心不全発症予測アルゴリズムを作成した。

【結果】2017 年 8 月から 2020 年 3 月までに 214 例が登録され、化学療法開始後 6 ヶ月までの評価が終了した 60 例(平均年齢 55.2±12.6 [SD] 歳、全例女性)で検討を行った(観察期間中央値 12 ヵ月)。癌治療関連心不全(左室駆出率 10%以上の低下かつ 53%未満と定義)の発生はアントラサイクリン系抗癌剤投与群の 4 例(6.7%)で認めた。癌治療関連心不全発症群は、非発症群と比較し、化学療法開始 3 ヶ月後の血清トロポニン T 値が有意に高値であったが(0.027 [0.019, 0.039] vs. 0.014 [0.009, 0.019] ng/mL, P=0.03)、一方で血漿 BNP 値および左室長軸方向グローバルストレインに有意差を認めなかった(34.4 [10.6, 150] vs. 13.4 [7.4, 23.2] pg/mL, P=0.32; -17.4±3.4 vs.19.8±2.8 %, P=0.25)。また化学療法前の native T1 値が癌治療関連心不全発症群において有意に高値であった(1,365±24 vs. 1,281±32, P=0.003)。CART 解析により、化学療法前の native T1 値(> 1,343 msec)と化学療法開始 3 ヵ月後の心筋トロポニン T 値(> 0.012 ng/mL)を組み合わせた予測アルゴリズムを作成した。

【結論】native T1 値(化学療法前)による癌治療関連心不全発症リスクの層別化と心筋トロポニンによる薬剤性心筋障害の評価(化学療法中)は、癌治療関連心不全発症の予測に有用と考えられた。

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