Prognostic value of tumor markers and ctDNA in patients with resectable gastric cancer receiving perioperative treatment: results from the CRITICS trial

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DOI

  • Astrid E. Slagter, Netherlands Cancer Institute
  • ,
  • Marieke A. Vollebergh, Netherlands Cancer Institute
  • ,
  • Irene A. Caspers, Netherlands Cancer Institute, University of Amsterdam
  • ,
  • Johanna W. van Sandick, Netherlands Cancer Institute
  • ,
  • Karolina Sikorska, Netherlands Cancer Institute
  • ,
  • Pehr Lind, Karolinska Institutet
  • ,
  • Marianne Nordsmark
  • Hein Putter, Leiden University
  • ,
  • Jeffrey P.B.M. Braak, Leiden University
  • ,
  • Elma Meershoek-Klein Kranenbarg, Leiden University
  • ,
  • Cornelis J.H. van de Velde, Leiden University
  • ,
  • Edwin P.M. Jansen, Netherlands Cancer Institute
  • ,
  • Annemieke Cats, Netherlands Cancer Institute
  • ,
  • Hanneke W.M. van Laarhoven, University of Amsterdam
  • ,
  • Nicole C.T. van Grieken, University of Amsterdam
  • ,
  • Marcel Verheij, Netherlands Cancer Institute, Radboud University Nijmegen

Aim: To evaluate the prognostic value of tumor markers in a European cohort of patients with resectable gastric cancer. Methods: We performed a post hoc analysis of the CRITICS trial, in which 788 patients received perioperative therapy. Association between survival and pretreatment CEA, CA 19-9, alkaline phosphatase, neutrophils, hemoglobin and lactate dehydrogenase were explored in uni- and multivariable Cox regression analyses. Likelihoods to receive potentially curative surgery were investigated for patients without elevated tumor markers versus one of the tumor markers elevated versus both tumor markers elevated. The association between tumor markers and the presence of circulating tumor DNA (ctDNA) was explored in 50 patients with available ctDNA data. Results: In multivariable analysis, in which we corrected for allocated treatment and other baseline characteristics, elevated pretreatment CEA (HR 1.43; 95% CI 1.11–1.85, p < 0.001) and CA 19-9 (HR 1.79; 95% CI 1.42–2.25, p < 0.001) were associated with worse OS. Likelihoods to receive potentially curative surgery were 86%, 77% and 60% for patients without elevated tumor marker versus either elevated CEA or CA 19-9 versus both elevated, respectively (p < 0.001). Although both preoperative presence of ctDNA and tumor markers were prognostic for survival, no association was found between these two parameters. Conclusion: CEA and CA 19-9 were independent prognostic factors for survival in a large cohort of European patients with resectable gastric cancer. No relationship was found between tumor markers and ctDNA. These factors could potentially guide treatment choices and should be included in future trials to determine their definitive position. Trial registration: ClinicalTrial.gov identifier: NCT00407186. EudraCT number: 2006-00413032.

OriginalsprogEngelsk
TidsskriftGastric Cancer
Vol/bind25
Nummer2
Sider (fra-til)401-410
Antal sider10
ISSN1436-3291
DOI
StatusUdgivet - mar. 2022

Bibliografisk note

Funding Information:
We thank all the patients, treating physicians, and research support staff in all the participating centers. This research was supported by the Dutch Cancer Society, the Dutch Clorectal Cancer Group and Hoffmann La Roche. The funding source had no role in the design, collection, analysis and interpretation of the data.

Funding Information:
N.C.T. van Grieken reported receiving grants from the Dutch Cancer Society and The Netherlands Organisation for Health Research and Development, and serving on an advisory board for Bristol-Myers Squibb and Merck Sharp and Dohme. H.W.M. van Laarhoven reported receiving grants/medication support from Bayer, BMS, Celgene, Janssen, Lilly, Merck, Nordic Pharma, Philips, Roche, Servier, and serving on an advisory board for BMS, Lilly, MSD, Nordic Pharma, Novartis, Servier E.P.M. Jansen, A. Cats and M. Verheij reported receiving grants from the Dutch Cancer Society, the Dutch Colorectal Cancer Group and Hoffmann La Roche.

Publisher Copyright:
© 2021, The Author(s).

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