Prediction of aggressiveness and treatment resistance by quantification of desmoplastic change in pancreatic ductal adenocarcinoma using iodine density images

• Project/Area Number: 19K08152
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Kobe University
• Principal Investigator: Sofue Keitaro 神戸大学, 医学部附属病院, 准教授 (90622027)
• Co-Investigator(Kenkyū-buntansha): 村上 卓道 神戸大学, 医学研究科, 教授 (20252653) ; 上嶋 英介 神戸大学, 医学部附属病院, 助教 (40645561) ; 上野 嘉子 神戸大学, 医学研究科, 助教 (50625134) ; 増田 充弘 神戸大学, 医学研究科, 講師 (60512530)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 膵癌 / 線維化定量 / 予後予測 / 線維性間質 / ヨードマップ / バイオマーカー / CT / Dual-Energy CT

Outline of Research at the Start

本研究の目的は，Dual-Energy CTで撮像したダイナミック造影CTから得られるヨードマップを用いて膵癌内部の線維性間質の多寡を定量測定することにより，非侵襲的に膵癌の悪性度ならびに治療抵抗性の予測を行うことである．
膵臓領域でもDual-Energy CTの平衡相から得られるヨードマップを用いて膵癌内部のヨード量を定量測定することで，従来のSingle-Energy CTで造影効果をCT値によって評価する方法と比較して正確・精細な評価を行うことができ，膵癌の中でも特に予後不良で治療抵抗性な症例を非侵襲的に層別化することが可能となり，膵癌における治療戦略の発展ならびに病態解明に寄与できる

Outline of Final Research Achievements

EVG staining to evaluate the amount of collagen and α-SMA staining to evaluate activated pancreatic stellate cells were performed on 162 patients with pancreatic ductal carcinoma who had undergone surgical resection. It was also found that pancreatic cancers with advanced fibrosis had more CD8-positive T cells in the tumor. These results suggest that pancreatic cancer patients with advanced fibrosis had better prognosis and may be related to the immune status within the tumor. In order to evaluate fibrotic stroma in detail from equilibrium phase images, we developed software for radiomic analysis based on MatLab.
Quantitative measurement of iodine content in pancreatic cancer using iodine maps obtained from the equilibrium phase of contrast-enhanced CT makes it possible to noninvasively stratify poor prognosis and treatment resistance in pancreatic cancers, and may contribute to the development of treatment strategies and clarification of pathological conditions in pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究結果において、膵癌においては線維化が高度な症例で予後が良く、腫瘍内免疫状態とも関連している可能性が示唆された。また、Dual-energy CTでは造影剤の停滞をより正確に定量できる可能性がファントム実験ならびに臨床患者の検討において証明された。
造影CTの平衡相から得られるヨードマップを用いて膵癌内部のヨード量を定量測定することで膵癌の中でも特に予後不良で治療抵抗性な症例を非侵襲的に層別化することが可能となる。本研究で実施している手法は膵癌における治療戦略の発展ならびに病態解明に寄与できる可能性があり，継続的な研究実行を行う予定である。

Research Products

• [Journal Article] Integrated analysis of tertiary lymphoid structures in relation to tumor-infiltrating lymphocytes and patient survival in pancreatic ductal adenocarcinoma (2023)
  • Author(s): Tanaka T, Masuda A, Inoue J, Hamada T, Ikegawa T, Toyama H, Sofue K, Shiomi H, Sakai A, Kobayashi T, Tanaka S, Nakano R, Yamada Y, Ashina S, Tsujimae M, Yamakawa K, Abe S, Gonda M, Masuda S, Inomata N, Uemura H, Kohashi S, Nagao K, Kanzawa M, Itoh T, Ueda Y, Fukumoto T, Kodama Y
  • Journal Title: Journal of Gastroenterology Volume: 58 Issue: 3 Pages: 277-291
  • DOI: 10.1007/s00535-022-01939-8
  • Peer Reviewed
• [Journal Article] Estimation of pancreatic fibrosis and prediction of postoperative pancreatic fistula using extracellular volume fraction in multiphasic contrast-enhanced CT (2022)
  • Author(s): Sofue K, Ueshima E, Masuda A, Shirakawa S, Zen Y, Ueno Y, Tsujita Y, Yamaguchi T, Yabe S, Tanaka T, Inomata N, Toyama H, Fukumoto T, Kodama Y, Murakami T.
  • Journal Title: Eur Radiol. Volume: 32(3) Issue: 3 Pages: 1770-1780
  • DOI: 10.1007/s00330-021-08255-4
  • Peer Reviewed
• [Journal Article] Acute pancreatitis in intraductal papillary mucinous neoplasms correlates with pancreatic volume and epithelial subtypes (2021)
  • Author(s): Tanaka T, Masuda A, Sofue K, Toyama H, Shiomi H, Sakai A, Kobayashi T, Tanaka S, Nakano R, Yamada Y, Ashina S, Tsujimae M, Yamakawa K, Abe S, Gonda M, Masuda S, Inomata N, Uemura H, Kohashi S, Nagao K, Kanzawa M, Itoh T, Fukumoto T, Kodama Y.
  • Journal Title: Pancreatology Volume: 21 Issue: 1 Pages: 138-143
  • DOI: 10.1016/j.pan.2020.11.005
  • Peer Reviewed
• [Journal Article] Prediction of pancreatic atrophy after steroid therapy using equilibrium-phase contrast computed tomography imaging in autoimmune pancreatitis (2020)
  • Author(s): Yamada Y, Masuda A, Sofue K, Ueshima E, Shiomi H, Sakai A, Kobayashi T, Ikegawa T, Tanaka S, Nakano R, Tanaka T, Kakihara M, Ashina S, Tsujimae M, Yamakawa K, Abe S, Gonda M, Masuda S, Inomata N, Kutsumi H, Itoh T, Murakami T, Kodama Y.
  • Journal Title: JGH Open Volume: 10 Issue: 4 Pages: 677-683
  • DOI: 10.1002/jgh3.12316
  • NAID: 120006884203
  • Peer Reviewed / Open Access
• [Presentation] 腹部領域のDual Energy CT (2021)
  • Author(s): 祖父江慶太郎
  • Organizer: 第57回日本医学放射線学会秋季臨床大会
  • Invited
• [Presentation] 造影CTによる肝線維化定量 (2021)
  • Author(s): 祖父江慶太郎
  • Organizer: 第35回東葛放射線画像セミナー
  • Invited
• [Presentation] Utility of Extracellular Volume Fraction Measured from Multiphasic Contrast-Enhanced Computed Tomography for the Estimation of Pancreatic Fibrosis. (2019)
  • Author(s): Sofue K, Ueno Y, Ueshima E, Tani R, Horinouchi H, Maruyama K, Okada T, Yamaguchi M, Sugimoto K, Murakami T.
  • Organizer: 105th Radiological Society of North America, Scientific Assembly and Annual Meeting.
  • Int'l Joint Research