TY - JOUR
T1 - Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer
AU - Hofste, Lisa S. M.
AU - Geerlings, Maartje J.
AU - von Rhein, Daniel
AU - Rütten, Heidi
AU - Westenberg, A. Helen
AU - Weiss, Marjan M.
AU - Gilissen, Christian
AU - Hofste, Tom
AU - van der Post, Rachel S.
AU - Klarenbeek, Bastiaan R.
AU - de Wilt, Johannes H. W.
AU - Ligtenberg, Marjolijn J. L.
AU - Garms, Linda
AU - Liem, Maite
AU - Rozema, Tom
AU - Wasowicz, Dareczka
AU - Burger, Pim
AU - Polat, Fatih
AU - Reijnders, Koen
AU - de Roos, Marnix
AU - Libic2 collaborators group
AU - Sietses, Colin
N1 - Funding Information: This work was supported by funding from Bergh in het Zadel Foundation and Sacha Swarttouw-Hijmans Foundation . The authors thank the Radboudumc Technology Center Genomics and the Netherlands Cancer Registry . Funding Information: 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.This work was supported by funding from Bergh in het Zadel Foundation and Sacha Swarttouw-Hijmans Foundation. The authors thank the Radboudumc Technology Center Genomics and the Netherlands Cancer Registry. Publisher Copyright: © 2023 The Authors
PY - 2023/7
Y1 - 2023/7
N2 - Introduction: 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. Materials and methods: 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. Results: 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). Conclusion: 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.
AB - Introduction: 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. Materials and methods: 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. Results: 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). Conclusion: 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.
KW - Circulating tumor DNA
KW - Liquid biopsies
KW - Neoadjuvant treatment
KW - Next-generation sequencing
KW - Rectal cancer
UR - http://www.scopus.com/inward/record.url?scp=85147411997&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejso.2023.01.026
DO - https://doi.org/10.1016/j.ejso.2023.01.026
M3 - Article
C2 - 36740555
SN - 0748-7983
VL - 49
SP - 1283
EP - 1290
JO - European Journal of Surgical Oncology
JF - European Journal of Surgical Oncology
IS - 7
ER -