Ito Keiichi, Masunaga Ayako, Tanaka Nobuyuki, Mizuno Ryuichi, Shirotake Suguru, Yasumizu Yota, Ito Yujiro, Miyazaki Yasumasa, Hagiwara Masayuki, Kanao Kent, Mikami Shuji, Momma Tetsuo, Masuda Takeshi, Nakagawa Ken, Oyama Masafumi, Asano Tomohiko, Oya Mototsugu
Department of Urology, National Defense Medical College, Saitama, Japan.
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Jpn J Clin Oncol. 2019 Jan 1;49(1):69-76. doi: 10.1093/jjco/hyy154.
Progression-free survival of first-line targeted therapy greatly influences the survival of patients with metastatic renal cell carcinoma. We evaluated whether post-treatment inflammatory markers and lactate dehydrogenase levels had impacts on progression-free survival prediction in addition to those of conventional predictors.
Two hundred and fifteen patients whose tumors were clear cell type and in whom first-line targeted therapies could be continued for >1 month were evaluated. Pretreatment clinical factors, pathological factors and laboratory data 1 month after targeted therapy initiation-including inflammatory markers (neutrophil count, neutrophil-to-lymphocyte ratio and C-reactive protein) and lactate dehydrogenase-were reviewed. To identify progression-free survival predictors, multivariate analyses were done.
The 1-year progression-free survival rate was 47%. Female gender, Karnofsky performance status <80%, time from diagnosis to systemic treatment <12 months, pretreatment C-reactive protein >3.0 mg/dl and post-treatment neutrophil-to-lymphocyte ratio >3.0 were independent predictors for progression-free survival. In contrast, neither C-reactive protein increase nor neutrophil-to-lymphocyte ratio increase after targeted therapy initiation were independent predictors. Pretreatment lactate dehydrogenase, post-treatment lactate dehydrogenase and lactate dehydrogenase decline were not independent predictors. When all patients were stratified by these independent factors into three groups (0 risk vs. 1 or 2 risks vs. 3 or more risks), there were significant differences in progression-free survival rates between the groups (P < 0.0001). Furthermore, there were also significant differences in overall survival rates between the groups (P < 0.0001).
Integration of post-treatment neutrophil-to-lymphocyte ratio value with pretreatment factors may lead to the establishment of effective predictive model for disease progression in patients with metastatic clear cell renal cell carcinoma who received first-line targeted therapies.
一线靶向治疗的无进展生存期对转移性肾细胞癌患者的生存有很大影响。我们评估了治疗后炎症标志物和乳酸脱氢酶水平除了传统预测指标外，是否对无进展生存期预测有影响。
评估了215例肿瘤为透明细胞型且一线靶向治疗可继续进行超过1个月的患者。回顾了治疗前的临床因素、病理因素以及靶向治疗开始后1个月的实验室数据，包括炎症标志物（中性粒细胞计数、中性粒细胞与淋巴细胞比值和C反应蛋白）和乳酸脱氢酶。为了确定无进展生存期的预测指标，进行了多变量分析。
1年无进展生存率为47%。女性、卡诺夫斯基功能状态<80%、从诊断到全身治疗的时间<12个月、治疗前C反应蛋白>3.0mg/dl以及治疗后中性粒细胞与淋巴细胞比值>3.0是无进展生存期的独立预测指标。相比之下，靶向治疗开始后C反应蛋白升高和中性粒细胞与淋巴细胞比值升高均不是独立预测指标。治疗前乳酸脱氢酶、治疗后乳酸脱氢酶和乳酸脱氢酶下降均不是独立预测指标。当所有患者根据这些独立因素分为三组（0个风险因素组 vs. 1个或2个风险因素组 vs. 3个或更多风险因素组）时，各组间的无进展生存率有显著差异（P<0.0001）。此外，各组间的总生存率也有显著差异（P<0.0001）。
将治疗后中性粒细胞与淋巴细胞比值与治疗前因素相结合，可能有助于为接受一线靶向治疗的转移性透明细胞肾细胞癌患者建立有效的疾病进展预测模型。
