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  • [Clin Cancer Res.] Prognostic Impact of Residual HPV ctDNA Detection after Chemoradiotherapy for Anal Squamous Cell Carcinoma.

    Institut Curie / Luc Cabel*

  • 출처
    Clin Cancer Res.
  • 등재일
    2018 Nov 15
  • 저널이슈번호
    24(22):5767-5771. doi: 10.1158/1078-0432.CCR-18-0922. Epub 2018 Jul 27.
  • 내용

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    Abstract
    Purpose: Chemoradiotherapy (CRT) is the current standard of care for patients diagnosed with locally advanced anal squamous cell carcinoma (ASCC), but some patients develop local and/or distant relapse during follow-up. This study was designed to monitor human papillomavirus (HPV) circulating tumor DNA (ctDNA) levels during CRT in patients with ASCC.Experimental Design: We analyzed samples from patients with HPV16- or HPV18-positive locally advanced ASCC. Blood samples were collected before and after CRT. HPV16 or HPV18 ctDNA detection was performed by droplet digital-PCR.Results: HPV ctDNA was detected before CRT in 29 of 33 patients with stages II-III ASCC [sensitivity: 88%; 95% confidence interval (CI), 72-95]; ctDNA positivity rate was associated with tumor stage (64% and 100% in stages II and III, respectively; P = 0.008). Among ctDNA-positive patients at baseline, ctDNA levels were higher in N+ than in N- tumors (median 85 copies/mL, range = 8-9,333 vs. 32 copies/mL, range = 3-1,350; P = 0.03). ctDNA detection at baseline had no significant prognostic impact. After CRT, three of 18 (17%) patients displayed residual detectable HPV ctDNA; ctDNA detection after CRT was strongly associated with shorter disease-free survival (P < 0.0001).Conclusions: This is the first proof-of-concept study assessing the prognostic value of ctDNA after CRT in locally advanced ASCC. In most patients, HPV ctDNA can be detected before CRT and becomes undetectable during CRT. In this study, we show that residual ctDNA levels after CRT are associated with very poor outcome.

     


    Author information

    Cabel L#1,2, Jeannot E#3, Bieche I3, Vacher S3, Callens C3, Bazire L4, Morel A5, Bernard-Tessier A3, Chemlali W3, Schnitzler A3, Lièvre A6, Otz J4, Minsat M4, Vincent-Salomon A3, Pierga JY5,7, Buecher B5, Mariani P8, Proudhon C9, Bidard FC1,2,9, Cacheux W5.
    1
    Department of Medical Oncology, Institut Curie, PSL Research University, Paris, Saint Cloud, France. luc.cabel@curie.fr fcbidard@curie.fr.
    2
    UVSQ, Paris-Saclay University, Saint Cloud, France.
    3
    Department of Pathology and Genetics, Institut Curie, PSL Research University, Paris, Saint Cloud, France.
    4
    Department of Radiotherapy, Institut Curie, PSL Research University, Paris, Saint Cloud, France.
    5
    Department of Medical Oncology, Institut Curie, PSL Research University, Paris, Saint Cloud, France.
    6
    Department of Gastroenterology, CHU Pontchaillou, Rennes 1 University, Rennes, France.
    7
    Paris Descartes University, Paris, France.
    8
    Department of Surgery, Institut Curie, PSL Research University, Paris, France.
    9
    Circulating Tumor Biomarkers Laboratory, Institut Curie, PSL Research University, Paris, France.
    #
    Contributed equally

  • 편집위원

    항문암에서 HPV ctDNA가 항암방사선치료 후 예후를 예측할 수 있음을 증명함

    2018-12-14 16:46:03

  • 편집위원

    HPV16 or HPV18 (+) anal cancer에서 CCRT 후 HPV circulating tumor DNA가 poor prognosis와 연관된다는 첫 연구결과이다.

    2018-12-14 17:00:40

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