Development of a diagnostic imaging system to evaluate tumor heterogeneity and tumor infiltrating lymphocytes

• Project/Area Number: 17K10550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: masumoto norio 広島大学, 病院(医), 助教 (40528014)
• Co-Investigator(Kenkyū-buntansha): 岡田 守人 広島大学, 原爆放射線医科学研究所, 教授 (70446045)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腫瘍浸潤リンパ球 / 超音波画像装置 / 乳癌 / 乳房専用PET / 腫瘍内不均一性 / 不均一性 / DbPET / 超音波検査 / 造影超音波検査 / 乳房PET / 不均一 / 造影超音波 / 乳腺外科

Outline of Final Research Achievements

The SUVs of DbPET are highly correlated with prognostic clinicopathological factors. This methodology can be used to visualize not only homogenous but also heterogeneous intratumoral FDG distributions of breast cancer. Moreover, pathological images of cancers with heterogeneous intratumoral distributions confirm that invasive cancer is present at sites of strong FDG uptake, while sites with weak uptake are more likely to have necrosis and fibrosis. We conclude that the intratumoral heterogeneity on DbPET can predict the malignancy grade of breast cancer.
The presence of TILs is predictive of prognosis and therapeutic effect for breast cancer. Our method for determining the TILs-US score based on conventional US findings was found to be an accurate and convenient diagnostic method for LPBC and can be easily performed preoperatively. The clinical application of the TILs-US score in LPBC is expected to lead to a new treatment strategy for breast cancer.

Academic Significance and Societal Importance of the Research Achievements

腫瘍には、腫瘍内不均一性をはじめとした問題により、既存の評価法には限界があり、新たな評価法の確立が国際社会より望まれており喫緊の課題である。乳房専用PET（DbPET)による画像検査と病理像を比較検証することで、DbPETは腫瘍の不均一性を予測できること、そして腫瘍の増殖能や悪性度を予測できることを実証した。また腫瘍の予後予測因子である腫瘍浸潤リンパ球(TILs)を多く持つ腫瘍には、超音波検査で特徴的所見があることを同定した。そしてその特徴的超音波画所見を組み合わせることで、TILsを予測できることを実証した。

Research Products

• [Journal Article] Novel tumor-infiltrating lymphocytes ultrasonography score based on ultrasonic tissue findings predicts tumor-infiltrating lymphocytes in breast cancer (2019)
  • Author(s): Fukui K, Masumoto N, Shiroma N, Kanou A, Sasada S, Emi A, Kadoya T, Yokozaki M, Arihiro K, Okada M.
  • Journal Title: Breast Cancer Volume: 26 Issue: 5 Pages: 573-580
  • DOI: 10.1007/s12282-019-00958-3
  • Peer Reviewed / Open Access
• [Journal Article] The relationship between ring-type dedicated breast PET and immune microenvironment in early breast cancer (2019)
  • Author(s): Sasada S, Shiroma N, Goda N, Kajitani K, Emi A, Masumoto N, Kadoya T, Arihiro K, Okada M.
  • Journal Title: Breast Cancer Res Treat Volume: 177 Issue: 3 Pages: 651-657
  • DOI: 10.1007/s10549-019-05339-0
  • Peer Reviewed / Open Access
• [Journal Article] Which type of breast cancers is undetectable on ring-type dedicated breast PET? (2018)
  • Author(s): Sasada S, Masumoto N, Goda N, Kajitani K, Emi A, Kadoya T, Okada M
  • Journal Title: Clin Imaging Volume: 51 Pages: 186-191
  • DOI: 10.1016/j.clinimag.2018.05.010
  • Peer Reviewed / Open Access
• [Journal Article] Intratumoral heterogeneity on dedicated breast positron emission tomography predicts malignancy grade of breast cancer (2018)
  • Author(s): Masumoto N, Kadoya T, Sasada S, Emi A, Arihiro K, Okada M
  • Journal Title: Breast Cancer Res Treat Volume: 171 Issue: 2 Pages: 315-323
  • DOI: 10.1007/s10549-018-4791-1
  • Peer Reviewed / Open Access
• [Journal Article] Dedicated breast PET for detecting residual disease after neoadjuvant chemotherapy in operable breast cancer: A prospective cohort study (2018)
  • Author(s): Shinsuke Sasada, Norio Masumoto, Noriko Goda, Keiko Kajitani, Akiko Emi, Takayuki Kadoya, Morihito Okada
  • Journal Title: European Journal of Surgical Oncology Volume: 44 Issue: 4 Pages: 444-448
  • DOI: 10.1016/j.ejso.2018.01.014
  • Peer Reviewed / Open Access
• [Journal Article] Intratumoral heterogeneity on dedicated breast positron emission tomography predicts malignancy grade of breast cancer (2018)
  • Author(s): Norio Masumoto,Takayuki Kadoya,Shinsuke Sasada,Akiko Emi, Koji Arihiro, Morihito Okada
  • Journal Title: Breast Cancer Research and Treatment Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Role of 18F-PET/CT in Predicting Prognosis of Patients With Breast Cancer After Neoadjuvant Chemotherapy (2017)
  • Author(s): Etsushi Akimoto, Takayuki Kadoya, Keiko Kajitani, Akiko Emi, Hideo Shigematsu, Masahiro Ohara, Norio Masumoto, Morihito Okada
  • Journal Title: Clinical Breast Cancer Volume: 18 Issue: 1 Pages: 45-52
  • DOI: 10.1016/j.clbc.2017.09.006
  • Peer Reviewed / Open Access
• [Presentation] Contrast-enhanced ultrasonography after two cycles of chemotherapy predicts the outcome of neoadjuvant chemotherapy in Triple-negative breast cancer (2019)
  • Author(s): Mai Nishina, Norio Masumoto, Akiko Kanou, Kayo Fukui, Yuri Kimura, Ai Amioka, Tomoko Itagaki, Shinsuke Sasada, Akiko Emi, Takayuki Kadoya, Morihito Okada
  • Organizer: San Antonio Breast Cancer Symposium 2019
• [Presentation] Ringlike uptake appearance on dedicated breast positron emission tomography before chemotherapy predicts outcome of neoadjuvant chemotherapy in breast cancer (2019)
  • Author(s): Norio Masumoto, Takayuki Kadoya, Mai Nishina, Yuri Kimura, Ai Amioka, Tomoko Itagaki, Shinsuke Sasada, Akiko Emi, Morihito Okada
  • Organizer: European Society for Medical Oncology Cancer Congress 2019
• [Presentation] 腫瘍浸潤リンパ球tumor-infiltrating lymphocytes (TILs)を示す乳癌の超音波画像の特徴～TILs-US score～CEUSの観点から (2019)
  • Author(s): 福井 佳与,舛本 法生,城間 紀之,横山 枝杏華 加納 昭子,笹田 伸介,恵美 純子,角舎 学行 横崎 典哉,有廣 光司,岡田 守人
  • Organizer: 第43回日本乳腺甲状腺超音波医学会学術集会
• [Presentation] 造影超音波検査は乳癌術前化学療法の 早期効果判定に応用出来るのか (2019)
  • Author(s): 舛本法生、角舎学行、福井佳与、加納昭子、末岡智志、鈴木江梨、 郷田紀子、笹田伸介、恵美純子、岡田守人
  • Organizer: 日本超音波医学会第92回学術集会
• [Presentation] Fractal解析による乳房専用PETの腫瘍内不均一性評価における乳癌の悪性度予測の検討 (2019)
  • Author(s): 舛本 法生, 角舎 学行, 末岡 智志, 鈴木 江梨, 郷田 紀子, 笹田 伸介, 梶谷 桂子, 恵美 純子, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 第27回日本乳癌学会学術総会
• [Presentation] 乳癌の腫瘍内不均一性を評価するための乳房専用PETの検討 (2018)
  • Author(s): 舛本法生, 角舎学行, 仁科麻衣、木村優里、末岡智志、鈴木江梨、郷田紀子, 笹田伸介、梶谷桂子、恵美純子、春田るみ、片岡健、岡田守人
  • Organizer: 第26回日本乳癌学会学術総会
• [Presentation] 非浸潤癌に対する乳房専用PETの有用性についての検討 (2018)
  • Author(s): 末岡 智志, 舛本 法生, 仁科 麻衣, 木村 優里, 鈴木 江梨, 郷田 紀子, 笹田 伸介, 梶谷 桂子, 恵美 純子, 角舎 学行, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 第26回日本乳癌学会学術総会
• [Presentation] 乳癌診療のための新しい乳癌画像診断 非浸潤癌または、腫瘍径1cm以下の乳癌に対する乳房専用PETの有用性についての検討 (2018)
  • Author(s): 末岡 智志, 舛本 法生, 仁科 麻衣, 木村 優里, 鈴木 江梨, 郷田 紀子, 笹田 伸介, 梶谷 桂子, 恵美 純子, 角舎 学行, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] Intratumoral heterogeneity on dedicated breast positron emission tomography before chemotherapy predicts the outcome of neoadjuvant chemotherapy in breast cancer (2018)
  • Author(s): Norio Masumoto, Takayuki Kadoya, Eri Suzuki, Satoshi Sueoka, Noriko Goda, ,Shinsuke Sasada, Akiko Emi, Rumi Haruta, Tsuyoshi Kataoka, Morihito Okada
  • Organizer: ESMO 2018 Congress
  • Int'l Joint Research
• [Presentation] Relationship between ring-type dedicated breast PET and tumor-infiltrating lymphocytes in early breast cancer (2018)
  • Author(s): Shinsuke Sasada, Noriyuki Shiroma, Eri Suzuki, Satoshi Sueoka,Noriko Goda, Keiko Kajitani, Akiko Emi, Norio Masumoto, Takayuki Kadoya, Rumi Haruta, Tsuyoshi Kataoka, Koji Arihiro, Morihito Okada
  • Organizer: ESMO 2018 Congress
  • Int'l Joint Research
• [Presentation] Histology and detectability on ring-type dedicated breast PET in breast cancer (2018)
  • Author(s): Yuri Kimura, Shinsuke Sasada, Noriko Goda, Akiko Emi, Norio Masumoto, Takayuki Kadoya, Rumi Haruta, Tsuyoshi Kataoka, Koji Arihiro, Morihito Okada
  • Organizer: ESMO 2018 Congress
  • Int'l Joint Research
• [Presentation] TILs-US score using ultrasonography before chemotherapy predicts the outcome of neoadjuvant treatment in HER2 positive breast cancer (2018)
  • Author(s): Norio Masumoto, Takayuki Kadoya, Akiko Kanou, Kayo Fukui, Noriyuki Shiroma, Satoshi Sueoka , Eri Suzuki , Goda Noriko,Shinsuke Sasada, Akiko Emi, Rumi Haruta , Tsuyoshi Kataoka, Koji Arihiro, Morihito Okada
  • Organizer: 2018 San Antonio Breast Cancer Symposium
  • Int'l Joint Research
• [Presentation] Characteristics of lymphocyte-predominant breast cancer in ultrasound images and their application to diagnostic prediction (2018)
  • Author(s): Kayo Fukui ，Norio Masumoto ，Noriyuki Shiroma ，Akiko Kanou ，Michiya Yokozaki ，Shinsuke Sasada ，Akiko Emi ，Takayuki Kadoya ，Koji Arihiro ，Morihito Okada
  • Organizer: 2018 San Antonio Breast Cancer Symposium
  • Int'l Joint Research
• [Presentation] The TILs-US scores based on ultrasonography can predict lymphocyte-predominant breast cancer before surgery (2018)
  • Author(s): Akiko Kanou, Norio Masumoto, Noriyuki Shiroma, Kayo Fukui, Shinsuke Sasada, Akiko Emi, Takayuki Kadoya, Michiya Yokozaki, Kouji Arihiro, Morihito Okada
  • Organizer: 2018 San Antonio Breast Cancer Symposium
  • Int'l Joint Research
• [Presentation] 乳房専用PETにおける乳癌術前評価の有用性についての検討 (2017)
  • Author(s): 舛本 法生, 角舎 学行, 村上 千佳, 吉川 徹, 藤原 誠, 半田 良憲, 網岡 愛, 郷田 紀子, 河野 美保, 笹田 伸介, 梶谷 桂子, 恵美 純子, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 第25回日本乳癌学会学術総会
• [Presentation] 乳癌術前化学療法における造影超音波検査の早期効果判定についての有用性 (2017)
  • Author(s): 舛本 法生, 角舎 学行, 吉川 徹, 村上 千佳, 網岡 愛, 郷田 紀子, 笹田 伸介, 恵美 純子, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 117回 日本外科学会定期学術集会
• [Presentation] Evaluation of pathological malignancy grade and neoplastic progress of breast cancer using dedicated breast positron emission tomography (2017)
  • Author(s): Norio Masumoto, Takayuki Kadoya, Mai Nishina, Yuri Kimura, Eri Suzuki, Satoshi Sueoka, Noriko Goda, Shinsuke Sasada, Keiko Kajitani, Akiko Emi, Rumi Haruta, Tsuyoshi Kataoka, Morihito Okada
  • Organizer: 2017 San Antonio Breast Cancer Symposium
  • Int'l Joint Research
• [Presentation] 腫瘍浸潤性リンパ球tumor-infiltrating lymphocytesを示す乳がんの超音波画像の検討 (2017)
  • Author(s): 福井佳与，舛本法生，加納昭子，笹田伸介，恵美純子，角舎学行，岡田守人， 城間紀之，有廣光司，横崎典哉
  • Organizer: 第38回日本乳腺甲状腺超音波医学会学術集会
• [Presentation] Detection ability of dedicated breast positron emission tomography for small-sized breast cancer (2017)
  • Author(s): Satoshi Sueoka, Norio Masumoto, Mai Nishina, Yuri Kimura, Eri Suzuki, Noriko Goda, Shinsuke Sasada, Keiko Kajitani, Akiko Emi, Rumi Haruta, Takayuki Kadoya, Tsuyoshi Kataoka, Morihito Okada
  • Organizer: 2017 San Antonio Breast Cancer Symposium
  • Int'l Joint Research
• [Presentation] 乳房専用PETによる乳癌術前の広がり診断の検討 (2017)
  • Author(s): 笹田 伸介, 角舎 学行, 網岡 愛, 郷田 紀子, 恵美 純子, 梶谷 桂子, 舛本 法生, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 117回 日本外科学会定期学術集会
• [Presentation] 術前乳房専用PET検査における病変範囲診断の検討 (2017)
  • Author(s): 笹田 伸介, 角舎 学行, 村上 千佳, 吉川 徹, 藤原 誠, 半田 良憲, 網岡 愛, 郷田 紀子, 河野 美保, 恵美 純子, 梶谷 桂子, 舛本 法生, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 第25回日本乳癌学会学術総会
• [Presentation] 手術可能乳癌の腫瘍浸潤リンパ球(TIL)におけるTreg分画の検討 (2017)
  • Author(s): 郷田 紀子, 河野 美保, 網岡 愛, 村上 千佳, 梶谷 桂子, 恵美 純子, 舛本 法生, 笹田 伸介, 厚井 裕美子, 平岡 恵美子, 小林 美恵, 角舎 学行, 城間 紀之, 有広 光司, 岡田 守人
  • Organizer: 第25回日本乳癌学会学術総会
• [Presentation] 乳房専用PETを用いた乳癌術前化学療法における効果予測の有用性についての検討 (2017)
  • Author(s): 藤原 誠, 角舎 学行, 村上 千佳, 吉川 徹, 半田 良憲, 網岡 愛, 郷田 紀子, 河野 美保, 恵美 純子, 梶谷 桂子, 舛本 法生, 春田 るみ, 片岡 健, 岡田 守人
  • Organizer: 第25回日本乳癌学会学術総会