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

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 (P_interaction=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.