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 ¹, Mahsoem Ali ¹

¹Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands; Cancer Center, Amsterdam, the Netherlands.
²Department of Health, SAS Institute B.V., Huizen, the Netherlands.
³Cancer Center, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands.
⁴Cancer Center, Amsterdam, the Netherlands; Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands.
⁵Department of Radiology, Sint Maartenskliniek, Nijmegen, the Netherlands.
⁶Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
⁷Department of Hepatobiliary, Transplantation, and Endocrine Surgery, Antwerp University Hospital, Antwerp, Belgium.
⁸Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands.
⁹Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands.
¹⁰Department of Surgery, OLVG Hospital, Amsterdam, the Netherlands.
¹¹Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
¹²Department of Medical Imaging, Radboud University Medical Center, Radboud University Nijmegen, Nijmegen, the Netherlands.
¹³Department of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, the Netherlands.
¹⁴Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands.
¹⁵Department of Surgery, Máxima Medical Center, Veldhoven, the Netherlands.
¹⁶Department of Surgery, Medical Spectrum Twente, Enschede, the Netherlands.
¹⁷Department of Interventional Radiology, St Antonius Hospital, Nieuwegein, the Netherlands.
¹⁸Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St Antonius Hospital, Nieuwegein, the Netherlands.
¹⁹Department of Surgery, Isala Hospital, Zwolle, the Netherlands.
²⁰Department of Surgery, Amphia Hospital, Breda, the Netherlands.
²¹Department of Surgery, Radboud University Medical Center, Radboud University Nijmegen, Nijmegen the Netherlands.
²²Department of Medical Oncology, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands.
²³Cancer Center, Amsterdam, the Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Medical Oncology, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands.
²⁴Cancer Center, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands.
²⁵Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands.

⁰Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands; Cancer Center, Amsterdam, the Netherlands.

European Journal of Cancer +

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September 5, 2025

View abstract on PubMed

Summary

Total tumor volume (TTV) is a superior predictor of overall survival (OS) and treatment response in colorectal liver metastases (CRLM) compared to RECIST1.1. TTV also helps personalize treatment selection for unresectable CRLM patients.

Area Of Science

Oncology
Medical Imaging
Clinical Trials

Background

Colorectal liver metastases (CRLM) present a significant clinical challenge, particularly when unresectable.
Current treatment response assessment relies on RECIST1.1, which may have limitations in accurately predicting outcomes.
Personalized treatment strategies are crucial for improving survival in CRLM patients.

Purpose Of The Study

To evaluate if total tumor volume (TTV) is a better measure than RECIST1.1 for assessing treatment response in unresectable CRLM.
To investigate TTV's potential as a predictive biomarker for selecting optimal systemic treatment regimens.
To compare the prognostic and predictive value of TTV and RECIST1.1 in the CAIRO5 trial.

Main Methods

Analysis of 425 patients with initially unresectable liver-only CRLM from the CAIRO5 phase 3 trial.
Calculation of baseline TTV and changes in TTV and RECIST1.1 from CT scans.
Multivariable Cox regression models were used to assess prognostic and predictive values.

Main Results

Baseline TTV and its relative change were the strongest independent predictors of overall survival (OS).
RECIST1.1 was not independently associated with OS in multivariable analyses.
Higher baseline TTV predicted a greater OS benefit from bevacizumab-based regimens over panitumumab-based regimens.

Conclusions

Total tumor volume (TTV) outperforms traditional risk factors and RECIST1.1 in predicting OS for unresectable CRLM.
TTV is a more accurate and sensitive method for treatment response assessment in CRLM.
TTV assessment shows promise for individualizing treatment decisions, particularly between bevacizumab and panitumumab.

Keywords:

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