Michiel Zeeuw J, Kemna Ruby, Ali Mahsoem, van Eck Sophie, Wesdorp Nina J, Roor Joran, van Waesberghe Jan Hein T M, van den Bergh Janneke E, Nota Irene M G C, Moos Shira I, van Dieren Susan, van Amerongen Martinus J, Bond Marinde J G, Chapelle Thiery, van Dam Ronald M, Engelbrecht Marc R W, Gerhards Michael F, Grunhagen Dirk J, van Gulik Thomas M, Hermans John J, de Jong Koert P, Klaase Joost M, Kok Niels F M, Leclercq Wouter K G, Liem Mike S L, van Lienden Krijn P, Quintus Molenaar I, Patijn Gijs A, Rijken Arjen M, Ruers Theo M, Verhoef Cornelis, de Wilt Johannes H W, Buffart Tineke E, Swijnenburg Rutger-Jan, Punt Cornelis J A, Verpalen Inez M, Stoker Jaap, Huiskens Joost, Kazemier Geert
Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands; Cancer Center, Amsterdam, the Netherlands.
Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands; Cancer Center, Amsterdam, the Netherlands.
Eur J Cancer. 2025 Oct 1;228:115738. doi: 10.1016/j.ejca.2025.115738. Epub 2025 Aug 21.
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.
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=0.017).
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.
本研究旨在评估在结直肠癌肝转移（CRLM）患者的治疗反应评估中，总肿瘤体积（TTV）是否优于RECIST1.1，并研究TTV作为初始不可切除CRLM个体患者最佳全身治疗方案的预测生物标志物。
纳入来自3期CAIRO5试验（NCT02162563）的初始不可切除的单纯肝转移CRLM患者。所有患者均接受诱导全身治疗。使用全身治疗前和首次随访时的CT扫描计算基线TTV以及TTV和RECIST1.1对全身治疗的反应变化，并通过多变量Cox回归模型评估其预后和预测价值。结果共纳入425例患者。在多变量分析中，基线TTV（100 mL与10 mL的调整后HR [aHR]，2.44 [95% CI，1.25 - 4.76]；P = 0.006）和TTV的相对变化是总生存期（OS）的最强预测因素（0%变化与50%降低的aHR，2.57 [1.83 - 3.60]；P < 0.0001）。相比之下，RECIST1.1与OS无独立相关性（部分缓解与疾病进展的aHR，0.63 [95% CI，0.33 - 1.20]）。较高的基线TTV预测FOLFOX - /FOLFIRI - 贝伐单抗与FOLFOX - /FOLFIRI - 帕尼单抗相比对OS有更强的治疗益处（P = 0.017）。
本研究表明，TTV（i）在OS预后方面优于传统危险因素，并且（ii）与目前用于初始不可切除CRLM患者的RECIST1.1系统相比，可能是一种更准确、更敏感的治疗反应评估方法。此外，TTV评估是在贝伐单抗和帕尼单抗之间进行个体化临床决策的一种有前景的方法。
