超音波検査技術

ISSN: 1881-4506
一般社団法人日本超音波検査学会
〒162-0801 東京都新宿区山吹町358-5
Japanese Journal of Medical Ultrasound Technology 40(6): 637-648 (2015)
doi:10.11272/jss.40.637

原著Researcher's Award - Original Article

造影超音波検査による乳癌術前化学療法効果判定の有用性The Usefulness of Contrast-enhanced Ultrasound for the Evaluation of Response to Neoadjuvant Chemotherapy in Breast Cancer

佐藤 恵美1,2，西田 睦2,3，工藤 悠輔2,3，井上 真美子2,3，表原 里実2,3，堀江 達則1,2，岩井 孝仁2,3，加藤 扶美4，細田 充主5，畑中 佳奈子6，山下 啓子5Megumi Satoh1,2, Mutsumi Nishida2,3, Yusuke Kudou2,3, Mamiko Inoue2,3, Satomi Omotehara2,3, Tatsunori Horie1,2, Takahito Iwai2,3, Fumi Kato4, Mitsuchika Hosoda5, Kanako Hatanaka6, Hiroko Yamashita5

1 北海道大学病院放射線部Division of Radiology, Hokkaido University Hospital ◇ 〒060-8648 北海道札幌市北区北十四条西五丁目Kita-14-Nishi 5, Kita-ku, Sapporo-shi, Hokkaido 060-8648, Japan

2 北海道大学病院超音波センターDiagnostic Center for Sonography, Hokkaido University Hospital ◇ 〒060-8648 北海道札幌市北区北十四条西五丁目Kita-14-Nishi 5, Kita-ku, Sapporo-shi, Hokkaido 060-8648, Japan

3 北海道大学病院検査・輸血部Division of Clinical Laboratory and Transfusion Medicine, Hokkaido University Hospital ◇ 〒060-8648 北海道札幌市北区北十四条西五丁目Kita-14-Nishi 5, Kita-ku, Sapporo-shi, Hokkaido 060-8648, Japan

4 北海道大学病院放射線診断科Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital ◇ 〒060-8648 北海道札幌市北区北十四条西五丁目Kita-14-Nishi 5, Kita-ku, Sapporo-shi, Hokkaido 060-8648, Japan

5 北海道大学病院乳腺外科Department of Breast Surgery, Hokkaido University Hospital ◇ 〒060-8648 北海道札幌市北区北十四条西五丁目Kita-14-Nishi 5, Kita-ku, Sapporo-shi, Hokkaido 060-8648, Japan

6 北海道大学病院病理部Department of Surgical Pathology, Hokkaido University Hospital ◇ 〒060-8648 北海道札幌市北区北十四条西五丁目Kita-14-Nishi 5, Kita-ku, Sapporo-shi, Hokkaido 060-8648, Japan

受付日：2015年3月31日Received: March 31, 2015
受理日：2015年8月12日Accepted: August 12, 2015
発行日：2015年12月1日Published: December 1, 2015
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目的：造影超音波検査（CEUS）による乳癌術前化学療法（NAC）の治療効果判定に関する有用性について明らかにすること．

対象・方法：2012年9月～2013年6月までに，NAC後に乳腺CEUSを施行し，外科的切除を行った乳癌33例35結節（全例女性，平均年齢49.5±12.1歳）を対象とした．造影剤はSonazoid®を0.015 mL/kg体重を投与し，投与後1分間撮像した．腫瘍内で最も強く造影効果を認める部位に3 mm径の円形関心領域（ROI）を設定し時間輝度曲線（TIC）を作成し，治療後のTime to peak（TTP, s），Mean transit time（MTT, s）を算出した．病理組織学的治療効果判定（組織判定）は乳癌取扱い規約第17版に則りGrade 0～3に分類し，Grade 3を完全奏効群，Grade 2以下を非完全奏効群に群別し，CEUSの各項目との比較検討を行った．また，RECISTガイドラインに準じてUS，造影MRIで腫瘍最大径を計測し治療効果を組織判定と比較した．統計学的検討はMann–WhitneyのU検定，Spearman順位相関係数にて行い，有意水準は5%未満とした．

結果：組織判定は，完全奏効群6結節，非完全奏効群29結節であった．CEUSによる治療後評価でTTP（平均値±SD，範囲）は完全奏効群11.7±4.7 s，4.7～19.7 s，非完全奏効群6.0±3.0 s，2.9～14.1 sで有意差を認めた（p=0.006）．MTT（平均値±SD，範囲）においても完全奏効群75.7±72.0 s，17.2～158.8 s，非完全奏効群15.6±12.5 s，4.3～57.7 sで有意差を認めた（p=0.007）．組織判定とTTP（ρ=0.613, p<0.01），MTT（ρ=0.698, p<0.01）間には中等度の有意な相関が認められた．

USによるRECIST評価はPD 1結節，SD 7結節，PR 27結節，CR 0結節．造影MRIによるRECIST評価は，PD 1結節，SD 8結節，PR 22結節，CR4結節であった．RECIST評価とTTP，MTTとの間には有意な相関関係は認められなかった．

結語：CEUSは，乳癌NAC後治療効果判定に有用である可能性が示唆された．

Purpose: To assess the feasibility of contrast-enhanced ultrasound (CEUS) with Sonazoid® for the evaluation of response to neoadjuvant chemotherapy in breast cancer patients.

Subjects and Methods: Thirty-three patients (all women, mean age 49.5 years) with 35 histologically confirmed breast cancers were evaluated. The enhancement patterns of the lesions were stored for 1 minute after bolus injection of the micro bubble contrast agent “Sonazoid®”. Time intensity curve (TIC) analysis was performed by placing the region of interest (ROI) at showing the strongest enhancement region. Time to peak (TTP, s) and mean transit time (MTT, s) were calculated. Histological evaluation of treatment response (HE) was graded from 0 to 3 according to the Japanese breast cancer guideline. The HE was further categorized into 2 groups; grade 0 to 2 was for a non-complete responder and grade 3 was for a complete responder. The Response Evaluation Criteria in Solid Tumors (RECIST) by ultrasonography (US) and contrast-enhanced MRI were also performed. Each CEUS value was compared between complete responders and non-complete responders. Statistical analysis was performed by the Mann–Whitney U test and Spearmann's rank correlation (p<0.05 was considered significant).

Results and Discussion: The HE values of responders and non-complete responders were 6 and 29 nodules, respectively. Respective post-treatment evaluation by CEUS of TTP (mean±SD, range) and MTT values were: responders, 75.7±72.0 s, 17.2 to 158.8 s and 75.7±72.0 s, 17.2 to 158.8 s: and non-complete responders, 6.0±3.0 s, 2.9 to 14.1 s and 15.6±12.5 s, 4.3 to 57.7 s. There were significant correlations between TTP and HE (ρ=0.613, p<0.01), and MTT and HE (ρ=0.698, p<0.01). Clinical response (RECIST) by US of PD, SD, PR and CR were 1, 7, 27, and 0, respectively. RECIST by US failed to detect CR. Clinical response (RECIST) by contrast-enhanced MRI of PD, SD, PR and CR were 1, 8, 22, and 4, respectively.

Conclusion: CEUS was judged to have a good potential for application to the evaluation of response to neoadjuvant chemotherapy in breast cancer patients.

Key words: contrast-enhanced ultrasound; breast cancer; response evaluation; time intensity curve; neoadjuvant chemotherapy

© 2015 一般社団法人日本超音波検査学会© 2015 Japanese Society of Sonographers

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