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Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.
Tie, Jeanne; Cohen, Joshua D; Lahouel, Kamel; Lo, Serigne N; Wang, Yuxuan; Kosmider, Suzanne; Wong, Rachel; Shapiro, Jeremy; Lee, Margaret; Harris, Sam; Khattak, Adnan; Burge, Matthew; Harris, Marion; Lynam, James; Nott, Louise; Day, Fiona; Hayes, Theresa; McLachlan, Sue-Anne; Lee, Belinda; Ptak, Janine; Silliman, Natalie; Dobbyn, Lisa; Popoli, Maria; Hruban, Ralph; Lennon, Anne Marie; Papadopoulos, Nicholas; Kinzler, Kenneth W; Vogelstein, Bert; Tomasetti, Cristian; Gibbs, Peter.
Afiliação
  • Tie J; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Cohen JD; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Lahouel K; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Lo SN; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Wang Y; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Kosmider S; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Wong R; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Shapiro J; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Lee M; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Harris S; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Khattak A; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Burge M; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Harris M; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Lynam J; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Nott L; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Day F; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Hayes T; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • McLachlan SA; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Lee B; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Ptak J; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Silliman N; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Dobbyn L; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Popoli M; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Hruban R; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Lennon AM; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Papadopoulos N; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Kinzler KW; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Vogelstein B; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Tomasetti C; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
  • Gibbs P; From the Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research (J.T., R.W., M.L., B.L., P.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre (J.T., B.L.), the Department of Medical Oncology, Western Health (J.T., S.K., M.L., P.G.), the Faculty of
N Engl J Med ; 386(24): 2261-2272, 2022 06 16.
Article em En | MEDLINE | ID: mdl-35657320
ABSTRACT

BACKGROUND:

The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.

METHODS:

We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 21 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use.

RESULTS:

Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not.

CONCLUSIONS:

A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quimioterapia Adjuvante / Neoplasias do Colo / DNA Tumoral Circulante / Antineoplásicos Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quimioterapia Adjuvante / Neoplasias do Colo / DNA Tumoral Circulante / Antineoplásicos Idioma: En Ano de publicação: 2022 Tipo de documento: Article