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Prediction of treatment effect of whole brain radiation therapy by plasma free DNA focused on genomic mutations

Research Project

Project/Area Number 21K15816
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionDokkyo Medical University

Principal Investigator

Hirano Yasuhiro  獨協医科大学, 医学部, 講師 (50593191)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords全脳照射 / 髄膜播種 / 血漿遊離腫瘍DNA / 中枢神経系転移 / 遺伝子変異
Outline of Research at the Start

肺癌の中枢神経系転移に対する放射線治療の効果は症例で異なる。
薬物療法耐性化後に生じた新たな遺伝子異常が放射線治療に対する交叉耐性に関与し、複数の遺伝子異常の組み合わせが予後に影響を及ぼすと想定されており、治療効果の違いを生む可能性があるが詳細は不明である。
本研究では肺癌中枢神経系転移例に対し、全脳照射前・後の血漿を用いた遺伝子パネルによるcirculating tumor DNA解析を行う。
肺癌診断時以降の治療経過中に獲得した様々なゲノム異常を捉え、その推移と治療効果・予後との関係を調べ、分子プロファイルと全脳照射の治療効果の関係を明らかにする。

Outline of Final Research Achievements

We studied the cases of whole-brain radiotherapy (WBRT) for leptomeningeal metastasis (LM) with lung adenocarcinoma. We retrospectively evaluated overall survival (OS) after WBRT and clinical variables, including EGFR/ALK status, in 80 consecutive patients who received WBRT for LM from lung adenocarcinoma at our institution between June 2013 and June 2021. We analyzed the following variables at the start of WBRT as the factors associated with OS and intracranial PFS: age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), EGFR/ALK status, presence of brain metastasis, presence of hydrocephalus, presence of extracranial metastasis, primary tumor control, and the number of systemic chemotherapy regimens (including central nervous system-penetrant EGFR and ALK tyrosine kinase inhibitors or immune checkpoint inhibitors) before WBRT. Multivariate analysis indicated that EGFR/ALK alterations and ECOG PS 0-1 were independent factors for favorable OS after WBRT.

Academic Significance and Societal Importance of the Research Achievements

肺癌中枢神経系転移は20~40%と高頻度であり、予後を決定する一因である。様々な背景因子が含まれ、放射線治療への反応性や予後が異なるが、全身状態や頭蓋外転移の有無などの既存の因子では全脳照射の効果予測は十分でない。
国立がん研究センター東病院で2013年6月から2021年6月までに肺腺癌の髄膜播種に全脳照射を施行した80症例の予後についての後方視的検討により、髄膜播種に対する全脳照射後の予後は不良であるが、パフォーマンスステータスが0-1、EGFR変異陽性またはALK転座陽性の患者において長期予後との関連が認められた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2023 2022

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Prognostic impact of EGFR/ALK alterations in leptomeningeal metastasis from lung adenocarcinoma treated with whole-brain radiotherapy2023

    • Author(s)
      Oyoshi Hidekazu、Hirata Hidenari、Hirano Yasuhiro、Zenda Sadamoto、Zhou Yuzheng、Tomizawa Kento、Fujisawa Takeshi、Nakamura Masaki、Hojo Hidehiro、Motegi Atsushi、Kageyama Shun-Ichiro、Zenke Yoshitaka、Goto Koichi、Ishihara Shunichi、Naganawa Shinji、Akimoto Tetsuo
    • Journal Title

      Clinical & Experimental Metastasis

      Volume: 40 Issue: 5 Pages: 407-413

    • DOI

      10.1007/s10585-023-10225-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] Prognosis after Whole-Brain Radiotherapy for Leptomeningeal Metastasis in Patients with Lung Adenocarcinoma with or without EGFR/ALK Alterations2022

    • Author(s)
      Hidekazu Oyoshi, Hidenari Hirata, Yasuhiro Hirano, Sadamoto Zenda, Takeshi Fujisawa, Masaki Nakamura, Hidehiro Hojo, Atsushi Motegi, Shun-ichiro Kageyama, Tetsuo Akimoto
    • Organizer
      American Society for Radiation Oncology ANNUAL MEETING 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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