Non-invasive therapeutic evaluation and treatment resistance mechanism of fertility-preserving progestin therapy for endometrial cancer

• Project/Area Number: 18K16763
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: University of Fukui
• Principal Investigator: Yamada Shizuka 福井大学, 学術研究院医学系部門(附属病院部), 特命助教 (40792643)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 子宮体癌 / FES-PET / 妊孕性温存 / 黄体ホルモン療法 / ホルモン療法 / ＦＥＳ－ＰＥＴ / 妊孕性温存療法

Outline of Final Research Achievements

16α-[18F]-fluoro-17β-estradiol (FES) is a radiopharmaceutical that binds to the estrogen receptor (ER) and is commonly used to prove the presence of ER-positive metastases. The aim of this study was to determine if FES positron emission tomography (PET) can predict the treatment response of fertility-sparing treatment with progestin in patients with atypical endometrial hyperplasia (AEH) and low-grade endometrial cancer (LGEC). The mean standardized uptake value (SUVmean) decreased greatly in patients with pathologically complete response (44.2%, 46.2%), while there was only a small change (22.5%) in the patient with pathologically stable disease. FES PET can be a non-invasive method to evaluate response to fertility-sparing progestin treatment.

Academic Significance and Societal Importance of the Research Achievements

プロゲステロン製剤を用いたホルモン療法は、増加傾向にある若年子宮体癌患者に対する唯一の妊孕性温存療法だが、その約4割が増悪・再発すること、治療効果判定として行う侵襲的な子宮内膜操作により自然妊娠率が低いことが問題になっている。本研究を通して腫瘍のFES集積変化がホルモン療法の治療効果と相関する傾向にあることがわかり、FES-PET検査により、ホルモン療法が有効となる症例を適切に選択し、さらに侵襲的な内膜操作を減らすことで治療後の妊娠率の改善にもつながる可能性が示唆された。

Research Products

• [Journal Article] エストロゲン受容体イメージングを用いた子宮体がんの新しい治療戦略 (2022)
  • Author(s): 山田しず佳、津吉秀昭、吉田好雄
  • Journal Title: Precision Medicine Volume: 5 Pages: 35-37
• [Journal Article] Prognostic value of 16α-[18F]-fluoro-17β-estradiol positron emission tomography as a predictor of disease outcome in endometrial cancer: A prospective study. (2020)
  • Author(s): Yamada S, Tsuyoshi H, Yamamoto M, Tsujikawa T, Kiyono Y, Okazawa H, Yoshida Y.
  • Journal Title: J Nucl Med Volume: 120 Issue: 5 Pages: 244319-244319
  • DOI: 10.2967/jnumed.120.244319
  • Peer Reviewed / Open Access
• [Journal Article] Predictive Value of 16α-[18F]-Fluoro-17β-Estradiol PET as a Biomarker of Progestin Therapy Resistance in Patients With Atypical Endometrial Hyperplasia and Low-Grade Endometrial Cancer (2019)
  • Author(s): Yamada Shizuka、Tsuyoshi Hideaki、Tsujikawa Tetsuya、Okazawa Hidehiko、Yoshida Yoshio
  • Journal Title: Clinical Nuclear Medicine Volume: 44 Issue: 7 Pages: 574-575
  • DOI: 10.1097/rlu.0000000000002612
  • Peer Reviewed
• [Presentation] Predictive value of FES PET as a biomarker of progestin therapy outcome in patients with early stage endometrial cancer (2020)
  • Author(s): Yamada Shizuka, Tsuyoshi Hideaki, Yoshida Yoshio
  • Organizer: 第72回日本産科婦人科学会学術講演会
• [Presentation] 子宮体癌におけるFES（16α-[18F]-fluoro-17β-estradiol ）-PETの有用性 (2020)
  • Author(s): 山田しず佳、津吉秀昭、加藤正隆、工藤渉、 佐々木晴菜、丹羽堅太郎、井上大輔、大沼利通、 品川明子、知野陽子、黒川哲司、吉田好雄
  • Organizer: 第28回福井婦人科腫瘍研究会
• [Presentation] Predictive value of FES PET as a biomarker of progestin therapy outcome in patients with early stage endometrial cancer (2020)
  • Author(s): Shizuka Yamada, Hideaki Tsuyoshi, Yoshio Yoshida
  • Organizer: 第72回日本産科婦人科学会学術講演会
• [Presentation] 若年子宮体癌の妊孕性温存療法に対する非侵襲的治療効果判定法の開発 (2018)
  • Author(s): 山田しず佳
  • Organizer: 第6回婦人科バイオマーカー研究会学術集会