Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Oct 1:228:115738.
doi: 10.1016/j.ejca.2025.115738. Epub 2025 Aug 21.

Total tumor volume predicts overall survival and response to induction chemotherapy in patients with colorectal cancer liver metastases: An ancillary study of the phase 3 CAIRO5 trial

J Michiel Zeeuw  1 , Ruby Kemna  2 , Mahsoem Ali  3 , Sophie van Eck  3 , Nina J Wesdorp  3 , Joran Roor  4 , Jan Hein T M van Waesberghe  5 , Janneke E van den Bergh  5 , Irene M G C Nota  5 , Shira I Moos  5 , Susan van Dieren  6 , Martinus J van Amerongen  7 , Marinde J G Bond  8 , Thiery Chapelle  9 , Ronald M van Dam  10 , Marc R W Engelbrecht  11 , Michael F Gerhards  12 , Dirk J Grunhagen  13 , Thomas M van Gulik  6 , John J Hermans  14 , Koert P de Jong  15 , Joost M Klaase  15 , Niels F M Kok  16 , Wouter K G Leclercq  17 , Mike S L Liem  18 , Krijn P van Lienden  19 , I Quintus Molenaar  20 , Gijs A Patijn  21 , Arjen M Rijken  22 , Theo M Ruers  16 , Cornelis Verhoef  13 , Johannes H W de Wilt  23 , Tineke E Buffart  24 , Rutger-Jan Swijnenburg  3 , Cornelis J A Punt  25 , Inez M Verpalen  26 , Jaap Stoker  26 , Joost Huiskens  27 , Geert Kazemier  3 ; CAIRO5 research group
Affiliations
Free article
Clinical Trial

Total tumor volume predicts overall survival and response to induction chemotherapy in patients with colorectal cancer liver metastases: An ancillary study of the phase 3 CAIRO5 trial

J Michiel Zeeuw et al. Eur J Cancer. .
Free article

Abstract

Introduction: This study aimed to assess whether total tumor volume (TTV) outperforms RECIST1.1 for treatment response assessment in patients with colorectal liver metastases (CRLM), and to investigate TTV as a predictive biomarker for the optimal systemic treatment regimen for individual patients with initially unresectable CRLM.

Methods: Patients with initially unresectable liver-only CRLM from the phase 3 CAIRO5 trial (NCT02162563) were included. All patients received induction systemic treatment. Baseline TTV and changes in TTV and RECIST1.1 in response to systemic treatment were calculated using the CT scans before systemic treatment and at first follow-up, and were assessed for their prognostic and predictive value with multivariable Cox regression models. Results In total, 425 patients were included. In multivariable analyses, baseline TTV (adjusted HR [aHR] for 100 mL vs 10 mL, 2.44 [95 % CI, 1.25-4.76]; P = 0.006) and relative change in TTV were the strongest predictors for OS (aHR for 0 % change vs 50 % decrease, 2.57 [1.83-3.60]; P < 0.0001). In contrast, RECIST1.1 was not independently associated with OS (aHR for partial response vs progressive disease, 0.63 [95 % CI, 0.33-1.20]). Higher baseline TTV predicted a stronger treatment benefit of FOLFOX-/FOLFIRI-bevacizumab vs FOLFOX-/FOLFIRI-panitumumab on OS (Pinteraction=0.017).

Conclusion: This study demonstrates that TTV (i) outperforms traditional risk factors for OS prognostication, and (ii) may be a more accurate and sensitive treatment response assessment method compared to the currently used RECIST1.1 system in patients with initially unresectable CRLM. Moreover, TTV assessment is a promising approach for individualized clinical decision-making between bevacizumab and panitumumab.

Keywords: Colorectal cancer; Liver metastases; Prognostic value; RECIST1.1; Systemic treatment; Total tumor volume; Tumor response assessment.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors of this manuscript declare relationships with the following companies: C.J.A.P. has an advisory role for Nordic Pharma. This funding is not related to the current research. The remaining authors declare no potential conflicts of interest.

Publication types

MeSH terms

Supplementary concepts

LinkOut - more resources