The Significance of ctDNA as a Predictor of Recurrence in Surgical Resection Cases Using Next-Generation Sequencing
| Project/Area Number |
20K17764
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Kindai University |
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Principal Investigator |
Ohara Shuta 近畿大学, 大学病院, 助教 (20813926)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | circulating tumor DNA / liquid biopsy / reccurence / surgery / lung cancer / Signatera / CAPP-Seq / NSCLC / Circurating tumor DNA / 肺癌 / 手術 / 再発 / 予後因子 / recurrence / next-generation sequence |
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| Outline of Research at the Start |
手術可能な肺がん患者は最も治癒の可能性が高いにも関わらず、その治療成績は満足すべきものではない。これは臨床的に検出できない微小な残存病巣が存在しているにも関わらず、それに対して有効な治療が行われていないことに起因する。手術可能な肺がん患者において循環血漿中のDNAの癌関連遺伝子異常が微小残存病巣のマーカーとなるかを検討する。臨床病期II期以上の患者70例の内、再発した20例に対し、次世代シーケンサーで解析をおこない、変異遺伝子コピー数の変化と手術、術後アジュバント治療、再発までの時間経過との関係を検討する。この結果に基づき前向きな術後補助療法の臨床試験を立案することを念頭においている。
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| Outline of Final Research Achievements |
In this study, we used CAPP-Seq and Signatera to evaluate the relationship between postoperative prognostic and ctDNA status and recurrence on imaging studies.
In a landmark analysis (median 9 days postoperatively, range 2-53 days), 5 patients tested positive for ctDNA and all recurred, with ctDNA positivity associated with a significantly worse prognosis. Five more patients tested positive for ctDNA during follow-up, and all relapsed. The prognosis was significantly worse if ctDNA was detected at least once during follow-up. Overall, the median lead time for ctDNA-positive imaging was 2.8 (0-12.8) months. ctDNA negativity was associated with a favorable outcome, with a long-term negative predictive value of 83.3% (30/36 patients).
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍残存病変を検出するためのcirculating tumor DNA（ctDNA）のモニタリングは、様々ながん種において再発予測や薬物療法の個別化などの面でその有用性が示されている。しかし、非小細胞肺がんにおけるその有効性については、十分なデータはない。本研究ではCAPP-SeqやSignateraを用いて術後の予後予測やctDNAの状態と画像検査における再発の関係を評価し,術後の採血ポイントを術後早期だけでなく、6か月毎におこなうことで、術後の予後予測だけでなく、術後再発の早期発見にctDNA解析が有用であることが示された。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Dose-dependence in acquisition of drug tolerant phenotype and high RYK expression as a mechanism of osimertinib tolerance in lung cancer2021
Author(s)
Ohara S, Suda K, Fujino T, Hamada A, Koga T, Nishino M, Chiba M, Shimoji M, Takemoto T, Soh J, Mitsudomi T
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Journal Title
Lung Cancer
Volume: 154
Pages: 84-91
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Prognostic implications of preoperative versus postoperative circulating tumor DNA in surgically resected lung cancer patients: a pilot study2020
Author(s)
Shuta Ohara, Kenichi Suda, Kazuko Sakai, Masaya Nishino, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Toshio Fujino,Takamasa Koga, Akira Hamada, Junichi Soh, Kazuto Nishio, Tetsuya Mitsudomi
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Journal Title
Translational Lung Cancer Research
Volume: 9
Issue: 5
Pages: 1915-1923
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic value of plasma fibrinogen and D-dimer levels in patients with surgically resected non-small cell lung cancer2020
Author(s)
Ohara S, Suda K, Tomizawa K, Takemoto T, Fujino T, Hamada A, Koga T, Nishino M, Chiba M, Sato K, Shimoji M, Soh J, Mitsudomi T
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Journal Title
Surgery Today
Volume: 50
Issue: 11
Pages: 1427-1433
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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