PDF(Pubmed)
Abstract：
With approval of anti-PD-1/PD-L1, metastatic non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. Since immune-related adverse events (irAEs) occur commonly in patients receiving anti-PD-1/PD-L1, the landscape of death causes may have changed in metastatic NSCLC. We aim to compare patterns of death causes in metastatic NSCLC between the pre-immunotherapy and immunotherapy era to identify the consequent landscape transition of death causes.
In this cohort study, 298,48patients with metastatic NSCLC diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results Program. Unsupervised clustering with Bayesian inference method was performed for all patients\' death causes, which separated them into two death patterns: the pre-immunotherapy era group and the immunotherapy era group. Relative risk (RR) of each death cause between two groups was estimated using Poisson regression. Reduced death risk as survival time was calculated with locally weighted scatterplot smooth (Lowess) regression.
Two patterns of death causes were identified by unsupervised clustering for all patients. Thus, we separated them into two groups, the immunotherapy era (2015-2017, N=40,172) and the pre-immunotherapy era (2000-2011, N=166,321), in consideration of obscure availability to immunotherapy for patients diagnosed in 2012-2014, when the follow-up cutoff was set as three years. Although all-cause death risk had reduced (29.2%, 13.7% and 27.8% for death risks of lung cancer, non-cancer and other cancers), non-cancer deaths in the immunotherapy era (N=2,100, 5.2%; RR=1.155, 95%CI: 1.101-1.211, P<0.001) significantly increased than that in the pre-immunotherapy era (N=7,249, 5.0%), which included causes of chronic obstructive pulmonary disease, cerebrovascular disease, pneumonia and influenza, septicemia, infectious diseases, accidents and adverse effects, hypertension, and chronic liver disease and cirrhosis. However, cancer-caused deaths (excluding lung cancer) had no significant changes.
The real-world landscape of death causes has changed in metastatic NSCLC when entering the immunotherapy era, and the increased non-cancer diseases may contribute to the changes that may be associated with commonly occurring irAEs.
In this cohort study, 298,48patients with metastatic NSCLC diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results Program. Unsupervised clustering with Bayesian inference method was performed for all patients\' death causes, which separated them into two death patterns: the pre-immunotherapy era group and the immunotherapy era group. Relative risk (RR) of each death cause between two groups was estimated using Poisson regression. Reduced death risk as survival time was calculated with locally weighted scatterplot smooth (Lowess) regression.
Two patterns of death causes were identified by unsupervised clustering for all patients. Thus, we separated them into two groups, the immunotherapy era (2015-2017, N=40,172) and the pre-immunotherapy era (2000-2011, N=166,321), in consideration of obscure availability to immunotherapy for patients diagnosed in 2012-2014, when the follow-up cutoff was set as three years. Although all-cause death risk had reduced (29.2%, 13.7% and 27.8% for death risks of lung cancer, non-cancer and other cancers), non-cancer deaths in the immunotherapy era (N=2,100, 5.2%; RR=1.155, 95%CI: 1.101-1.211, P<0.001) significantly increased than that in the pre-immunotherapy era (N=7,249, 5.0%), which included causes of chronic obstructive pulmonary disease, cerebrovascular disease, pneumonia and influenza, septicemia, infectious diseases, accidents and adverse effects, hypertension, and chronic liver disease and cirrhosis. However, cancer-caused deaths (excluding lung cancer) had no significant changes.
The real-world landscape of death causes has changed in metastatic NSCLC when entering the immunotherapy era, and the increased non-cancer diseases may contribute to the changes that may be associated with commonly occurring irAEs.
摘要：
随着抗PD-1/PD-L1的批准，转移性非小细胞肺癌（NSCLC）已进入免疫治疗时代。由于免疫相关的不良事件（irAE）通常发生在接受抗PD-1/PD-L1的患者中，因此转移性NSCLC的死亡原因可能已经改变。我们旨在比较免疫治疗前和免疫治疗时代转移性NSCLC的死亡原因模式，以确定随后的死亡原因的景观转变。
在这项队列研究中，从监测中确定了2000年至2018年诊断的298,48例转移性NSCLC患者，流行病学,和最终结果计划。对所有患者的死因进行了贝叶斯推断方法的无监督聚类，将它们分为两种死亡模式：免疫疗法前时代组和免疫疗法时代组。使用泊松回归估计两组之间每种死亡原因的相对风险（RR）。使用局部加权散点图平滑（Lowess）回归计算随着生存时间而降低的死亡风险。
通过对所有患者的无监督聚类确定了两种死亡原因模式。因此，我们把他们分成两组,免疫治疗时代（2015-2017，N=40,172）和免疫治疗前时代（2000-2011，N=166,321），考虑到2012-2014年确诊患者的免疫治疗有效性模糊,当时将随访截止时间设定为3年.尽管全因死亡风险降低了(29.2%，肺癌的死亡风险分别为13.7%和27.8%，非癌症和其他癌症)，免疫治疗时代的非癌症死亡（N=2,100，5.2％；RR=1.155，95CI：1.101-1.211，P<0.001）比免疫治疗前时代（N=7,249，5.0％）显着增加，其中包括慢性阻塞性肺疾病的病因，脑血管疾病，肺炎和流感，败血症,传染病,事故和不利影响，高血压,慢性肝病和肝硬化.然而,癌症导致的死亡(不包括肺癌)无显著变化.
进入免疫治疗时代后，转移性NSCLC的死亡原因的现实世界格局发生了变化，和增加的非癌症疾病可能有助于可能与常见的irAE相关的变化。
在这项队列研究中，从监测中确定了2000年至2018年诊断的298,48例转移性NSCLC患者，流行病学,和最终结果计划。对所有患者的死因进行了贝叶斯推断方法的无监督聚类，将它们分为两种死亡模式：免疫疗法前时代组和免疫疗法时代组。使用泊松回归估计两组之间每种死亡原因的相对风险（RR）。使用局部加权散点图平滑（Lowess）回归计算随着生存时间而降低的死亡风险。
通过对所有患者的无监督聚类确定了两种死亡原因模式。因此，我们把他们分成两组,免疫治疗时代（2015-2017，N=40,172）和免疫治疗前时代（2000-2011，N=166,321），考虑到2012-2014年确诊患者的免疫治疗有效性模糊,当时将随访截止时间设定为3年.尽管全因死亡风险降低了(29.2%，肺癌的死亡风险分别为13.7%和27.8%，非癌症和其他癌症)，免疫治疗时代的非癌症死亡（N=2,100，5.2％；RR=1.155，95CI：1.101-1.211，P<0.001）比免疫治疗前时代（N=7,249，5.0％）显着增加，其中包括慢性阻塞性肺疾病的病因，脑血管疾病，肺炎和流感，败血症,传染病,事故和不利影响，高血压,慢性肝病和肝硬化.然而,癌症导致的死亡(不包括肺癌)无显著变化.
进入免疫治疗时代后，转移性NSCLC的死亡原因的现实世界格局发生了变化，和增加的非癌症疾病可能有助于可能与常见的irAE相关的变化。
