Duke University, Durham, North Carolina.
MD Anderson Cancer Center, Houston, Texas.
Int J Radiat Oncol Biol Phys. 2022 Sep 1;114(1):60-74. doi: 10.1016/j.ijrobp.2022.03.020. Epub 2022 Mar 21.
Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly.
A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA.
Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies.
Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.
患有肺癌和脑转移的患者是一个明显异质的人群。准确的预后对于最佳个体化治疗至关重要。在之前的出版物中，我们描述了分级预后评估（GPA），但从未报道过小细胞肺癌（SCLC）的 GPA，在非小细胞肺癌（NSCLC）中，程序性死亡配体 1（PD-L1）的影响尚不清楚。这项工作的三个目的是提供 SCLC GPA 的初步报告，评估 PD-L1 对 NSCLC 患者生存的影响，并相应地更新 Lung GPA。
对 2015 年 1 月 1 日至 2020 年 12 月 31 日期间在 4183 名患有肺癌（3002 例腺癌、611 例非腺癌、570 例 SCLC）且新诊断为脑转移的患者进行了与生存相关的预后因素和治疗的多变量分析，使用了多机构回顾性数据库。使用有显著意义的变量来更新 Lung GPA。
肺腺癌、SCLC 和非腺癌的总体中位生存时间分别为 17、10 和 8 个月，但 GPA 为 2 至 52 个月的范围很广。在 SCLC 中，显著的预后因素是年龄、表现状态、颅外转移和脑转移的数量。在 NSCLC 中，肺腺癌患者的分子标志物分布和已知原发性肿瘤分子状态显示 PD-L1 50%至 100%、PD-L1 1%至 49%、表皮生长因子受体和间变性淋巴瘤激酶的改变/表达分别为 32%、31%、30%和 7%。肺腺癌和脑转移患者 PD-L1 表达为 0、1%至 49%和≥50%的中位生存时间分别为 17、19 和 24 个月（P<.01），证实 PD-L1 是一个预后因素。先前确定的 NSCLC 的预后因素（表皮生长因子受体和间变性淋巴瘤激酶状态、表现状态、年龄、脑转移数量和颅外转移）得到了再次证实。这些因素被纳入到更新的 Lung GPA 中，所有组织学的亚组之间都有稳健的分组。
患有肺癌和脑转移的患者的生存情况有所改善，但差异很大。目前报告了 SCLC 的 GPA。对于患有 NSCLC-腺癌和脑转移的患者，PD-L1 是一个新发现的重要预后因素，之前确定的因素得到了再次证实。更新后的指标为 SCLC、NSCLC-非腺癌和 NSCLC-腺癌（纳入 PD-L1）建立了独特的标准。更新的 Lung GPA 可在 brainmetgpa.com 上免费获得，为准确估计生存、个体化治疗和分层临床试验提供了一个工具。
