Analysis of chemoradiotherapy for lung cancer using liquid biopsy

• Project/Area Number: 19K17174
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kitagawa Mio 札幌医科大学, 医学部, 助教 (30608922)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 肺癌 / 放射線治療 / リキッドバイオプシー

Outline of Research at the Start

近年、放射線治療と併用する機会が増加している免疫チェックポイント阻害剤の治療効果のモニタリングや、放射線肺障害の発現予測において、リンパ球のRNA発現変化やリキッドバイオプシーを応用することで、肺がんに対する個別化放射線治療の実現を目指すため、
①放射線治療前後の血清中のエクソソーム内mRNA/miRNA発現を解析し、
②DNA損傷修復に関わるタンパクや免疫チェックポイントに関わるタンパク発現との関連
性を検討し、放射線治療効果や放射線性肺障害を予測することを目的とする。

Outline of Final Research Achievements

The aim of this study was to predict individualized radiotherapy response and radiation lung injury in patients with stage III unresectable non-small cell lung cancer treated with chemoradiotherapy and immunotherapy. 10 ml of peripheral blood was drawn in 10 patients before the start of treatment, at the end of chemoradiotherapy and 2 weeks after the first immunotherapy administration. PBMC fractions were isolated and RNA TCR sequences were analyzed to confirm changes over time.
The results showed that the mean observation period from the start of treatment exceeded 15 months, with 6 cases of CR and 4 cases of PD in the chemoradiotherapy plus immunotherapy group, and that the change in TCR lepatore over time tended to be greater in the CR cases than in the PD cases.

Academic Significance and Societal Importance of the Research Achievements

切除不能Ⅲ期肺癌の化学放射線療法および免疫療法を行った症例において、化学放射線療法前後および免疫療法前後でのTCRレパトアを調べることで、放射線治療の効果予測に利用できる可能性を示した。今後症例数を増やして、より高い精度での治療効果を予測する方法の確立を目指す。

Research Products

• [Journal Article] Combined chemoradiotherapy and programmed cell death-ligand 1 blockade leads to changes in the circulating T-cell receptor repertoire of patients with non-small-cell lung cancer. (2022)
  • Author(s): Someya M, Tokita S, Kanaseki T, Kitagawa M, Hasegawa T, Tsuchiya T, Fukushima Y, Gocho T, Kozuka Y, Mafune S, Ikeuchi Y, Takahashi M, Moniwa K, Matsuo K, Hasegawa T, Torigoe T, Sakata KI.
  • Journal Title: Cancer Sci. Volume: 113(12) Issue: 12 Pages: 4394-4400
  • DOI: 10.1111/cas.15566
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Radiotherapy for HPV-related cancers: prediction of therapeutic effects based on the mechanism of tumor immunity and the application of immunoradiotherapy (2022)
  • Author(s): Someya Masanori、Fukushima Yuki、Hasegawa Tomokazu、Tsuchiya Takaaki、Kitagawa Mio、Gocho Toshio、Mafune Shoh、Ikeuchi Yutaro、Kozuka Yoh、Hirohashi Yoshihiko、Torigoe Toshihiko、Iwasaki Masahiro、Matsuura Motoki、Saito Tsuyoshi、Sakata Koh-ichi
  • Journal Title: Japanese Journal of Radiology Volume: - Issue: 5 Pages: 458-465
  • DOI: 10.1007/s11604-021-01231-4
  • NAID: 210000178430
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy (2021)
  • Author(s): Someya Masanori、Tsuchiya Takaaki、Fukushima Yuki、Hasegawa Tomokazu、Hori Masakazu、Kitagawa Mio、Gocho Toshio、Mafune Shoh、Ikeuchi Yutaro、Hirohashi Yoshihiko、Torigoe Toshihiko、Iwasaki Masahiro、Matsuura Motoki、Saito Tsuyoshi、Matsumoto Yoshihisa、Sakata Koh-ichi
  • Journal Title: Medical Molecular Morphology Volume: 54 Issue: 3 Pages: 245-252
  • DOI: 10.1007/s00795-021-00290-w
  • Peer Reviewed
• [Journal Article] Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer (2020)
  • Author(s): Someya Masanori、Hasegawa Tomokazu、Tsuchiya Takaaki、Kitagawa Mio、Gocho Toshio、Fukushima Yuuki、Hori Masakazu、Miura Katsutoshi、Takada Yu、Nakata Kensei、Sakata Koh-ichi
  • Journal Title: Journal of Radiation Research Volume: 61 Issue: 2 Pages: 265-274
  • DOI: 10.1093/jrr/rrz099
  • Peer Reviewed / Open Access
• [Journal Article] Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy. (2020)
  • Author(s): Tsuchiya T, Someya M, Takada Y, Hasegawa T, Kitagawa M, Fukushima Y, Gocho T, Hori M, Nakata K, Hirohashi Y, Torigoe T, Saito T, Sakata KI.
  • Journal Title: Strahlenther Onkol. Volume: - Issue: 8 Pages: 725-735
  • DOI: 10.1007/s00066-019-01571-1
  • Peer Reviewed
• [Journal Article] Evaluation of the urethral α/β ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy. (2020)
  • Author(s): Gocho T, Hori M, Fukushima Y, Someya M, Kitagawa M, Hasegawa T, Tsuchiya T, Hareyama M, Takagi M, Hashimoto K, Masumori N, Sakata KI.
  • Journal Title: Brachytherapy Volume: Epub ahead of print Issue: 3 Pages: 290-297
  • DOI: 10.1016/j.brachy.2020.02.007
  • Peer Reviewed
• [Journal Article] Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy (2019)
  • Author(s): Kitagawa M, Someya M, Hasegawa T, Mikami T, Asaishi K, Hasegawa T, Matsumoto Y, Kutomi G, Takemasa I, Sakata K
  • Journal Title: Strahlentherapie und Oncologie Volume: - Issue: 7 Pages: 1-11
  • DOI: 10.1007/s00066-019-01468-z
  • Peer Reviewed
• [Journal Article] Efficacy of combined radiotherapy and anti‐programmed death 1 therapy in acral and mucosal melanoma (2019)
  • Author(s): Kato Junji、Hida Tokimasa、Someya Masanori、Sato Sayuri、Sawada Masahide、Horimoto Kohei、Fujioka Mao、Minowa Tomoyuki、Matsui Yoshiyuki、Tsuchiya Takaaki、Kitagawa Mio、Nakata Kensei、Sakata Koh‐ichi、Torigoe Toshihiko、Uhara Hisashi
  • Journal Title: The Journal of Dermatology Volume: 46 Issue: 4 Pages: 328-333
  • DOI: 10.1111/1346-8138.14805
  • Peer Reviewed / Open Access
• [Presentation] 末梢血リンパ球TCRレパトア解析を用いた3期NSCLCのCRT+ICI治療効果予測 (2023)
  • Author(s): 染谷正則、長谷川智一、北川未央、土屋正旭、福島悠希、後町俊夫、眞船翔、金関貴之、時田芹奈、坂田耕一
  • Organizer: 第82回日本医学放射線学会総会
• [Presentation] 局所進行非小細胞肺癌に対する化学放射線療法およびデュルバルマ ブ維持療法の初期経験 (2021)
  • Author(s): 北川未央、三浦勝利、佐々木文博、中野聡
  • Organizer: 日本放射線腫瘍学会第34回学術大会
• [Presentation] 根治放射線治療を行った進行期子宮頸癌症例における腫瘍免疫と予後との関連 (2020)
  • Author(s): 染谷 正則 土屋 高旭 福島 悠希 長谷川智一 北川 未央 後町 敏夫 堀 正和 坂田耕一
  • Organizer: 第32回日本放射線腫瘍学会学術大会