Abstract：
The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS).
Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed.
We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS (p < 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2-3 versus 0-1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 vs 7.9 months; median OS (mOS): 33.7 vs 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39-0.75; p < 0.001, respectively), while the impact on PFS resulted in borderline significance.
Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.
Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed.
We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS (p < 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2-3 versus 0-1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 vs 7.9 months; median OS (mOS): 33.7 vs 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39-0.75; p < 0.001, respectively), while the impact on PFS resulted in borderline significance.
Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.
摘要：
背景：免疫检查点抑制剂（ICIs）的出现彻底改变了转移性肾细胞癌（mRCC）的治疗前景。然而，靶向血管内皮生长因子（VEGF）轴的酪氨酸激酶抑制剂（TKIs）仍然起着关键作用。本研究的目的是探索综合血液评分的预后表现，基于血红蛋白（Hb）浓度，平均红细胞体积（MCV），和红细胞分布宽度(RDW)，抗VEGFTKIs治疗的mRCC患者。主要终点是Hb，MCV,和RDW的无进展生存期（PFS）和总生存期（OS）。
方法：我们的多中心回顾性观察性研究纳入了2012年1月至2020年12月在9个意大利中心接受帕唑帕尼或卡博替尼治疗的mRCC患者。临床记录和实验室数据，包括Hb水平，MCV,和RDW,在基线时收集。进行描述性统计以及单变量和多变量分析。
结果：我们招募了301例mRCC患者，其中179例（59％）接受了帕唑帕尼治疗，和122（41%）卡博替尼。我们认为基线Hb≥12g/dL，MCV>87fL,RDW≤16%是良好的预后因素；因此，开发一个能够划分4个不同类别的多参数分数。良好预后因素的数量与显著延长的PFS和OS相关(两者p<0.001)。因此,我们通过将病例分为两组(2-3和0-1,良好因子),制定了基于红细胞的评分.对PFS和OS的影响甚至更显著（中位数PFS（mPFS）：16.3比7.9个月；中位数OS（mOS）：33.7比14.1个月），不管是什么TKI特工.当受到单变量和多变量分析的挑战时，就OS而言，血液评分保持其较高的预后意义（OS的多变量分析HR：0.53，95％CI0.39-0.75；p<0.001），而对PFS的影响则具有临界意义。
结论：我们的分析证明了基于易于利用的血液参数的多参数评分的预后作用，如Hb浓度，MCV,和RDW。基于红细胞的评分可能是HIF-1α途径和VEGF轴上调的基础，从而确定可能受益于TKI治疗的选定人群。
方法：我们的多中心回顾性观察性研究纳入了2012年1月至2020年12月在9个意大利中心接受帕唑帕尼或卡博替尼治疗的mRCC患者。临床记录和实验室数据，包括Hb水平，MCV,和RDW,在基线时收集。进行描述性统计以及单变量和多变量分析。
结果：我们招募了301例mRCC患者，其中179例（59％）接受了帕唑帕尼治疗，和122（41%）卡博替尼。我们认为基线Hb≥12g/dL，MCV>87fL,RDW≤16%是良好的预后因素；因此，开发一个能够划分4个不同类别的多参数分数。良好预后因素的数量与显著延长的PFS和OS相关(两者p<0.001)。因此,我们通过将病例分为两组(2-3和0-1,良好因子),制定了基于红细胞的评分.对PFS和OS的影响甚至更显著（中位数PFS（mPFS）：16.3比7.9个月；中位数OS（mOS）：33.7比14.1个月），不管是什么TKI特工.当受到单变量和多变量分析的挑战时，就OS而言，血液评分保持其较高的预后意义（OS的多变量分析HR：0.53，95％CI0.39-0.75；p<0.001），而对PFS的影响则具有临界意义。
结论：我们的分析证明了基于易于利用的血液参数的多参数评分的预后作用，如Hb浓度，MCV,和RDW。基于红细胞的评分可能是HIF-1α途径和VEGF轴上调的基础，从而确定可能受益于TKI治疗的选定人群。
