Prognostic value of total tumor volume in patients with colorectal liver metastases: A secondary analysis of the randomized CAIRO5 trial with external cohort validation

J. Michiel Zeeuw*, Nina J. Wesdorp, Mahsoem Ali, Anne Joëlle J.J. Bakker, Kelly R. Voigt, Martijn P.A. Starmans, Joran Roor, Ruby Kemna, Jan Hein T.M. van Waesberghe, Janneke E. van den Bergh, Irene M.G.C. Nota, Shira I. Moos, Susan van Dieren, Martinus J. van Amerongen, Marinde J.G. Bond, Thiery Chapelle, Ronald M. van Dam, Marc R.W. Engelbrecht, Michael F. Gerhards, Thomas M. van GulikJohn J. Hermans, Koert P. de Jong, Joost M. Klaase, Niels F.M. Kok, Wouter K.G. Leclercq, Mike S.L. Liem, Krijn P. van Lienden, I. Quintus Molenaar, Gijs A. Patijn, Arjen M. Rijken, Theo M. Ruers, Johannes H.W. de Wilt, Inez M. Verpalen, Jaap Stoker, Dirk J. Grunhagen, Rutger Jan Swijnenburg, Cornelis J.A. Punt, Joost Huiskens, Cornelis Verhoef, Geert Kazemier

*Corresponding author for this work

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Abstract

Background: This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment. Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. Results: In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.

Original languageEnglish
Article number114185
JournalEuropean Journal of Cancer
Volume207
Early online date23 Jun 2024
DOIs
Publication statusPublished - Aug 2024

Keywords

  • Colorectal cancer
  • Liver metastases
  • Systemic therapy
  • Local treatment tumor volume
  • Prognostic marker

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