Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
JCO Precis Oncol. 2024 Jan;8:e2300256. doi: 10.1200/PO.23.00256.
We aimed to investigate the prognostic role of baseline and longitudinal levels of neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy + bevacizumab (CT + B) or chemotherapy only. Additionally, we investigated whether treatment outcomes were mediated by the longitudinal biomarker.
Data from an Italian randomized phase III trial were used. The main end point was progression-free survival (PFS). To address research questions, a series of joint models of longitudinal and survival data were specified, and the direct and indirect treatment effects were quantified.
Data for 239 patients, 113 (47.3%) treated with CT + B and 126 (52.7%) with CT only, were included in the analyses. The effect of NLR seemed to be mediated by the longitudinal trajectory of the biomarker. Only in the patient subgroup treated with CT + B, the baseline NLR retained a direct effect on PFS. Regarding the effect of treatment on PFS, two scenarios were observed. In the subgroup of patients with low baseline, NLR bevacizumab showed a direct protective effect only (hazard ratio [HR], 0.66 [95% CI, 0.45 to 0.98]), whereas in the subgroup with high baseline NLR, there was evidence for an adverse direct effect (HR, 1.63 [95% CI, 1.03 to 2.57]) and a protective indirect-which is mediated by the longitudinal biomarker-effect (HR, 0.71 [95% CI, 0.55 to 0.90]).
In our study, inflammatory indexes collected longitudinally showed a significant adverse prognostic role, thus suggesting the collection and use of such data for better clinical decision making. In the specific setting, we considered this is particularly important as the treatment effect seemed to be modified by both the baseline and longitudinal inflammation statuses. However, further research is needed to understand the possible factors underlying these results.
本研究旨在探讨化疗联合贝伐珠单抗（CT+ B）或单纯化疗治疗转移性结直肠癌（mCRC）患者基线和纵向中性粒细胞与淋巴细胞比值（NLR）水平的预后价值，并探讨治疗结局是否受到纵向生物标志物的影响。
本研究使用了意大利一项随机 III 期临床试验的数据。主要终点为无进展生存期（PFS）。为了回答研究问题，我们专门制定了一系列纵向和生存数据的联合模型，并对直接和间接治疗效果进行了量化。
共纳入了 239 例患者的数据，其中 113 例（47.3%）接受 CT+ B 治疗，126 例（52.7%）接受 CT 治疗。NLR 的作用似乎受到生物标志物纵向轨迹的影响。仅在接受 CT+ B 治疗的患者亚组中，基线 NLR 对 PFS 仍有直接影响。关于治疗对 PFS 的影响，观察到了两种情况。在基线 NLR 较低的患者亚组中，贝伐珠单抗仅显示出直接保护作用（危险比[HR]，0.66 [95%置信区间，0.45 至 0.98]），而在基线 NLR 较高的患者亚组中，存在直接不利作用（HR，1.63 [95%置信区间，1.03 至 2.57]）和通过纵向生物标志物介导的保护间接作用（HR，0.71 [95%置信区间，0.55 至 0.90]）。
在本研究中，纵向收集的炎症指标显示出显著的不良预后作用，因此表明收集和使用此类数据可以更好地进行临床决策。在特定环境下，我们认为这一点尤为重要，因为治疗效果似乎受到基线和纵向炎症状态的共同影响。然而，需要进一步的研究来理解这些结果背后的可能因素。
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