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Multiparameter analysis of tumor response to anti-PD-1 therapy with integrated PET/MRI in lung cancer

Research Project

Project/Area Number 19K08119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionUniversity of Fukui

Principal Investigator

Umeda Yukihiro  福井大学, 学術研究院医学系部門(附属病院部), 講師 (80401975)

Co-Investigator(Kenkyū-buntansha) 石塚 全  福井大学, 学術研究院医学系部門, 教授 (50302477)
岡沢 秀彦  福井大学, 高エネルギー医学研究センター, 教授 (50360813)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsFLT-PET / 非小細胞肺がん / 免疫治療 / 免疫チェックポイント阻害剤 / 肺癌 / FDG / FLT / PET / MRI / 効果判定
Outline of Research at the Start

①統合型PET/MRIを用い、非小細胞肺癌に対するPD-1抗体治療の早期効果判定を行う。治療前後にFLT及びCu-ATSM-PET/MRIを行い、PET及びMRIのパラメーターを測定し、これらとresponse evaluation criteria in solid tumors (RECIST)による奏効との関連、無増悪生存期間、全生存期間との関連を検討する。
②PD-1抗体治療後早期に増大が見られた場合、診断の目的で再生検を行い、治療前後の検体においてPD-1及びPD-L1の発現の程度やCD8+T細胞や制御性T細胞の腫瘍内密度を評価し、腫瘍内部の免疫反応の差を評価し画像変化の意味付けする。

Outline of Final Research Achievements

Anti-programmed death-1 (PD-1) therapy has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). However, it is difficult to evaluate the early response to anti-PD-1 therapy. We determined whether changes in 3′-deoxy-3′- [18F]-fluorothymidine (18F-FLT) PET parameters before and soon after treatment initiation predicted the therapeutic effect of anti-PD-1 antibody.
Patients with non-progressive disease (non-PD) had significantly decreased TLP at 2 weeks, and decreased SUVmax, PTV, and TLP at 6 weeks, compared to those with PD. Changes in 18F-FLT PET parameters may have value as an early predictive biomarker for the response to anti-PD-1 therapy in patients with NSCLC. However, it should be noted that pseudoprogression was observed in 18F-FLT PET imaging at 2 weeks after treatment initiation.

Academic Significance and Societal Importance of the Research Achievements

治療2週後でのFLT集積の変化は、その後の治療効果を中程度予測した。しかし、奏効した患者の37.5%にproliferative pseudoprogressionが認められた。治療6週後の18F-FLT集積の変化は、より強くその後の治療効果と関連した。PD-1抗体による炎症細胞の増殖の程度を測定することで、診断精度を高められる可能性がある。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2023 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Efficacy and safety of nanoparticle albumin‐bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non‐small cell lung cancer: A multicenter Phase 2 clinical trial2023

    • Author(s)
      Sonoda Tomoaki、Umeda Yukihiro、Demura Yoshiki、Tada Toshihiko、Nakashima Koki、Anzai Masaki、Yamaguchi Makiko、Shimada Akikazu、Ohi Masahiro、Honjo Chisato、Waseda Yuko、Akai Masaya、Ishizuka Tamotsu
    • Journal Title

      Cancer Medicine

      Volume: in print Issue: 12 Pages: 13041-13053

    • DOI

      10.1002/cam4.5978

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictive value of 3′-deoxy-3′-<sup>18</sup>F-fluorothymidine PET in the early response to anti-programmed death-1 therapy in patients with advanced non-small cell lung cancer2021

    • Author(s)
      Sato Masayuki、Umeda Yukihiro、Tsujikawa Tetsuya、Mori Tetsuya、Morikawa Miwa、Anzai Masaki、Waseda Yuko、Kadowaki Maiko、Kiyono Yasushi、Okazawa Hidehiko、Ishizuka Tamotsu
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 9 Issue: 7 Pages: e003079-e003079

    • DOI

      10.1136/jitc-2021-003079

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiological perspective of COVID‐19 pneumonia: The early features and progressive behaviour on high‐resolution CT2021

    • Author(s)
      Tsujikawa Tetsuya、Umeda Yukihiro、Itoh Harumi、Sakai Toyohiko、Iwasaki Hiromichi、Okazawa Hidehiko、Ishizuka Tamotsu、Kimura Hirohiko
    • Journal Title

      Journal of Medical Imaging and Radiation Oncology

      Volume: 65 Issue: 2 Pages: 208-212

    • DOI

      10.1111/1754-9485.13139

    • Related Report
      2021 Research-status Report 2020 Research-status Report
  • [Journal Article] Predictive value of integrated 18F-FDG PET/MRI in the early response to nivolumab in patients with previously treated non-small cell lung cancer.2020

    • Author(s)
      Umeda Y, Morikawa M, Anzai M, Ameshima S, Kadowaki M, Waseda Y, Shigemi H, Tsujikawa T, Kiyono Y, Okazawa H, Ishizuka T.
    • Journal Title

      J Immunother Cancer

      Volume: 8 Issue: 1 Pages: e000349-e000349

    • DOI

      10.1136/jitc-2019-000349

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and safety of immune checkpoint inhibitor monotherapy in pretreated elderly patients with non-small cell lung cancer.2020

    • Author(s)
      Yamaguchi O, Imai H, Minemura H, Suzuki K, Wasamoto S, Umeda Y, Osaki T, Kasahara N, Uchino J, Sugiyama T, Ishihara S, Ishii H, Naruse I, Mori K, Kotake M, Kanazawa K, Minato K, Kagamu H, Kaira K.
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 85 Issue: 4 Pages: 761-771

    • DOI

      10.1007/s00280-020-04055-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of first-line pembrolizumab monotherapy in elderly patients (aged > 75 years) with non-small cell lung cancer.2020

    • Author(s)
      Imai H, Wasamoto S, Yamaguchi O, Suzuki K, Sugiyama T, Uchino J, Minemura H, Osaki T, Ishii H, Umeda Y, Mori K, Kotake M, Kagamu H, Morozumi N, Taniguchi H, Kasai T, Minato K, Kaira K.
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: 146 Issue: 2 Pages: 457-466

    • DOI

      10.1007/s00432-019-03072-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The vertebral 3'-deoxy-3'-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer.2019

    • Author(s)
      Umeda Y, Tsujikawa T, Anzai M, Morikawa M, Waseda Y, Kadowaki M, Shigemi H, Ameshima S, Mori T, Kiyono Y, Okazawa H, Ishizuka T.
    • Journal Title

      Eur Radiol

      Volume: 29 Issue: 7 Pages: 3908-3917

    • DOI

      10.1007/s00330-019-06161-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] FLT-PET画像を用いたPD-1抗体治療による造血臓器の増殖能の変化に関する検討2021

    • Author(s)
      梅田幸寛、佐藤譲之、近澤亮、黒川紘輔、武田俊宏、三ツ井美穂、島田昭和、山口牧子、園田智明、本定千知、門脇麻衣子、早稲田優子、安齋正樹、辻川哲也、岡沢秀彦、石塚 全
    • Organizer
      第61回日本呼吸器学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] FLT-PET画像を用いたPD-1抗体治療による造血臓器の増殖能の変化に関する検討2021

    • Author(s)
      梅田幸寛、佐藤譲之、近澤亮、黒川紘輔、武田俊宏、三ツ井美穂、島田昭和、山口牧子、園田智明、本定千知、門脇麻衣子、早稲田優子、安齋正樹、辻川哲也、岡沢秀彦、石塚全
    • Organizer
      第61回日本呼吸器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] MRIを用いたSTIR画像による既治療非小細胞肺癌に対するニボルマブ療法の早期効果予測2019

    • Author(s)
      梅田幸寛
    • Organizer
      第60回日本肺癌学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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