Background: The neutrophil-lymphocyte ratio (NLR) is a well-known prognostic marker in various cancers. However, its role as a predictive marker for the effectiveness of nivolumab in patients with metastatic RCC (mRCC) remains unclear. We evaluated the relationships between the NLR and progression-free survival (PFS) or overall survival (OS) in mRCC patients treated with nivolumab. Methods: The data of 52 mRCC patients who received nivolumab therapy were collected from seven institutes and evaluated. The median follow-up period from treatment with nivolumab was 25.2 months (IQR 15.5-33.2). Results: The median duration of nivolumab therapy was 7.1 months (IQR 2.9-24.4). The objective response rate was 25% and the 1-and 2-year PFS rates were 46.2 and 25.2%, respectively. The median NLR values at baseline and 4 weeks were 3.7 (IQR 2.7-5.1) and 3.3 (IQR 2.4-5.7), respectively. In the multivariate analysis, an NLR of ≥3 at 4 weeks was an independent predictor of PFS (P = 0.013) and OS (P = 0.034). The 1-year PFS of patients with an NLR of < 3 at 4 weeks was better than that of those with an NLR of ≥3 (75% versus 29%, P = 0.011). The 1-year OS of patients with an NLR of < 3 at 4 weeks was also better than that of those with an NLR of ≥3 (95% versus 71%, P = 0.020). Conclusions: Although the baseline NLR was not associated with PFS or OS, an NLR of ≥3 at 4 weeks after the initiation of therapy might be a robust predictor of poor PFS and OS in mRCC patients undergoing sequential treatment with nivolumab.
Background:The neutrophil-lymphocyte ratio (NLR) is a well-known prognostic marker in various cancers. However, its role as a predictive marker for the effectiveness of nivolumab in patients with metastatic RCC (mRCC) remains unclear. We evaluated the relationships between the NLR and progression-free survival (PFS) or overall survival (OS) in mRCC patients treated with nivolumab. Methods: The data of 52 mRCC patients who received nivolumab therapy were collected from seven institutes and evaluated. The median follow-up period from treatment with nivolumab was 25.2 months (IQR 15.5-33.2). Results: The median duration of nivolumab therapy was 7.1 months (IQR 2.9-24.4). The objective response rate was 25% and the 1- and 2-year PFS rates were 46.2% and 25.2%, respectively. The median NLR values at baseline and 4 weeks were 3.7 (IQR 2.7-5.1) and 3.3 (IQR 2.4 -5.7), respectively. In the multivariate analysis, an NLR of ≥ 3 at 4 weeks was an independent predictor of PFS ( P = 0.013) and OS ( P = 0.034). The 1-year PFS of patients with an NLR of < 3 at 4 weeks was better than that of those with an NLR of ≥ 3 (75% versus 29%, P = 0.011). The 1-year OS of patients with an NLR of < 3 at 4 weeks was also better than that of those with an NLR of ≥ 3 (95% versus 71%, P = 0.020). Conclusions: Although the baseline NLR was not associated with PFS or OS, an NLR of ≥3 at 4 weeks after the initiation of therapy might be a robust predictor of poor PFS and OS in mRCC patients undergoing sequential treatment with nivolumab.
Backgrounds: For diagnosis of upper urinary tract urothelial carcinoma (UTUC), conventional ureteroscopic examinations are invasive, and selective urine cytology has insufficient sensitivity. We have developed a new anion-exchange column for high-performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. This method is expected to be very suitable for quantification of DNA methylation levels of cancer cells in urine samples with contamination of various cell lineages. Purpose: The aim of this study was to establish a less invasive and more accurate method for UTUC diagnosis based on DNA methylation quantification by our newly developed HPLC. Methods: Urine samples were collected by urinary catheterization during surgery for 218 urological cancer patients. Our previous studies have identified 4 CpG sites showing differences in DNA methylation levels between non-cancerous urothelium and UTUC based on genome-wide DNA methylation analysis using tissue specimens. In the present study, DNA methylation levels of these marker CpG sites were quantified by HPLC using the urine samples. Results: The thresholds have been set for the retention time by HPLC and the area under the chromatogram. Diagnostic criteria have been established to distinguish cases with current UTUC from non-urothelial cancer cases, bladder cancer cases and post-urothelial cancer treatment cases by combining marker CpG sites. The sensitivity and specificity were 90.9% and 87.0% respectively. Conclusions: Since HPLC-based DNA methylation diagnostic system was able to discriminate UTUC cells from blood cells and other contaminating cells in urine samples, application of our criteria will ultimately allow non-invasive diagnosis of UTUC in the clinical setting. It may be possible to at least partially replace highly invasive procedures such as ureteroscopy and to enable early initiation of treatment for UTUC resulting in improved prognosis. Citation Format: Mao Fujimoto, Eri Arai, Takuya Kikushima, Naotaka Nishiyama, Tomofumi Nakamura, Yuriko Yamada, Hiroaki Taira, Takuya Yotani, Hiroshi Kitamura, Yae Kanai. DNA methylation diagnostics for upper urinary tract urothelial carcinoma using newly developed high-performance liquid chromatography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6004.
Background: The neutrophil-lymphocyte ratio (NLR) is a well-known prognostic marker in various cancers. However, its role as a predictive marker for the effectiveness of nivolumab in patients with metastatic RCC (mRCC) remains unclear. We evaluated the relationships between the NLR and progression-free survival (PFS) or overall survival (OS) in mRCC patients treated with nivolumab. Methods: The data of 46 mRCC patients who received nivolumab therapy were collected from six institutes and evaluated. The median follow-up period from treatment with nivolumab was 12.5 months (IQR 10.0-16.7). Results: The median duration of nivolumab therapy was 6.5 months (IQR 3.3-13.7). The objective response rate was 22% and the 1- and 2-year PFS rates were 49.4% and 34.8%, respectively. The median NLR values at baseline and 4 weeks were 3.7 (IQR 2.7-5.2) and 3.7 (IQR 2.5-5.9), respectively. In the multivariate analysis, an NLR of ≥ 3 at 4 weeks was an independent predictor of PFS (P = 0.005) and OS (P = 0.031). The 1-year PFS of patients with an NLR of < 3 at 4 weeks was better than that of those with an NLR of ≥ 3 (83% versus 27%, P = 0.001). The 1-year OS of patients with an NLR of < 3 at 4 weeks was also better than that of those with an NLR of ≥ 3 (94% versus 71%, P = 0.002). Conclusions: Although the baseline NLR was not associated with PFS or OS, an NLR of ≥3 at 4 weeks after the initiation of therapy might be a robust predictor of poor PFS and OS in mRCC patients undergoing sequential treatment with nivolumab.
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