Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer.
Circulating tumor DNA
Liquid biopsies
Neoadjuvant treatment
Next-generation sequencing
Rectal cancer
Journal
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
ISSN: 1532-2157
Titre abrégé: Eur J Surg Oncol
Pays: England
ID NLM: 8504356
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
03
11
2022
revised:
30
12
2022
accepted:
24
01
2023
medline:
19
6
2023
pubmed:
6
2
2023
entrez:
5
2
2023
Statut:
ppublish
Résumé
Patients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices. Patients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured. Before treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression). These data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.
Identifiants
pubmed: 36740555
pii: S0748-7983(23)00093-8
doi: 10.1016/j.ejso.2023.01.026
pii:
doi:
Substances chimiques
Circulating Tumor DNA
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1283-1290Investigateurs
Linda Garms
(L)
Maite Liem
(M)
Tom Rozema
(T)
Dareczka Wasowicz
(D)
Pim Burger
(P)
Fatih Polat
(F)
Koen Reijnders
(K)
Marnix de Roos
(M)
Colin Sietses
(C)
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Prof. Marjolijn Ligtenberg received consulting fees from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Illumina, Janssen Pharmaceuticals, Lilly, Merck Sharp & Dohme and Roche. All these relations were not related to this study and were paid to the institution. Prof. Johannes de Wilt received research funding from Dutch Cancer Society, ZonMw and Metronic. These relations were not related to this study and were paid to the institution. All other authors declare that they have no conflict of interest.