Kim Jong Yeob, Lee Keum Hwa, Kang Jeonghyun, Borcoman Edith, Saada-Bouzid Esma, Kronbichler Andreas, Hong Sung Hwi, de Rezende Leandro Fórnias Machado, Ogino Shuji, Keum Nana, Song Mingyang, Luchini Claudio, van der Vliet Hans J, Shin Jae Il, Gamerith Gabriele
Yonsei University College of Medicine, Seoul 03722, Korea.
Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea.
Cancers (Basel). 2019 Nov 1;11(11):1699. doi: 10.3390/cancers11111699.
Hyperprogressive disease (HPD) is a recently acknowledged pattern of rapid tumor progression after the initiation of immune checkpoint inhibitors. HPD has been observed across various types of tumors and has been associated with poor survival. We performed a meta-analysis to identify baseline (i.e., prior to programmed cell death 1 [PD-1, PDCD1] / programmed cell death 1 ligand 1 [PD-L1, CD274] inhibitor therapy) patient factors associated with risks of developing HPD during PD-1/PD-L1 inhibitor therapy. We searched eight databases until 6 June 2019. We calculated the summary odds ratio (OR) and its 95% confidence interval (CI) using the random-effects model and explored between-study heterogeneity and small-study effects. A total of nine articles was eligible (217 HPD cases, 1519 cancer patients) for meta-analysis. There was no standard definition of HPD, and the incidence of HPD ranged from 1 to 30%. We identified twenty-three baseline patient factors, of which five factors were statistically significantly associated with HPD. These were serum lactate dehydrogenase (LDH) above the upper normal limit (OR = 1.89, 95% CI = 1.02-3.49, = 0.043), more than two metastatic sites (OR = 1.86, 1.34-2.57, < 0.001), liver metastases (OR = 3.33, 2.07-5.34, < 0.001), Royal Marsden Hospital prognostic score of 2 or above (OR = 3.33, 1.96-5.66, < 0.001), and positive PD-L1 expression status that was inversely correlated with HPD (OR = 0.60, 0.36-0.99, = 0.044). Between-study heterogeneity was low. Evidence of small-study effect was found in one association (PD-L1 expression). Subset analyses of patients with non-small cell lung cancer showed similar results. Future studies are warranted to identify underlying molecular mechanisms and to test their roles as predictive biomarkers of HPD.
超进展性疾病（HPD）是免疫检查点抑制剂开始使用后最近才被认识到的一种肿瘤快速进展模式。HPD已在各种类型的肿瘤中被观察到，并且与生存率低有关。我们进行了一项荟萃分析，以确定基线（即程序性细胞死亡蛋白1[PD-1，PDCD1]/程序性细胞死亡蛋白1配体1[PD-L1，CD274]抑制剂治疗前）患者因素与在PD-1/PD-L1抑制剂治疗期间发生HPD风险的相关性。我们检索了八个数据库直至2019年6月6日。我们使用随机效应模型计算汇总比值比（OR）及其95%置信区间（CI），并探讨研究间异质性和小研究效应。共有九篇文章符合荟萃分析的条件（217例HPD病例，1519例癌症患者）。HPD没有标准定义，HPD的发生率在1%至30%之间。我们确定了23个基线患者因素，其中五个因素与HPD在统计学上显著相关。这些因素包括血清乳酸脱氢酶（LDH）高于正常上限（OR = 1.89，95%CI = 1.02 - 3.49，P = 0.043）、转移部位超过两个（OR = 1.86，1.34 - 2.57，P < 0.001）、肝转移（OR = 3.33，2.07 - 5.34，P < 0.001）、皇家马斯登医院预后评分2分或以上（OR = 3.33，1.96 - 5.66，P < 0.001）以及与HPD呈负相关的PD-L1阳性表达状态（OR = 0.60，0.36 - 0.99，P = 0.044）。研究间异质性较低。在一个关联（PD-L1表达）中发现了小研究效应的证据。非小细胞肺癌患者的亚组分析显示了相似的结果。有必要进行进一步的研究以确定潜在的分子机制，并测试它们作为HPD预测生物标志物的作用。
