Minneapolis Radiation Oncology and University of Minnesota Gamma Knife Center, Minneapolis, MN.
MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2020 Nov 10;38(32):3773-3784. doi: 10.1200/JCO.20.01255. Epub 2020 Sep 15.
Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility.
A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively.
Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation ( < .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non-small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively.
Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient > 0.50).
由于担心较差的生存率可能掩盖有前途的治疗方法的益处，传统观念使患有脑转移的患者没有资格参加临床试验。我们的小组先前发表了特定于诊断的分级预后评估（GPA）。使用分子标志物和新确定的预后因素更新了更大的当代队列，并已发表。这项工作的目的是在一份报告中介绍所有更新的指标，以指导治疗选择、分层研究并定义扩展资格的资格系数。
一个包含 6984 名新发脑转移患者的多机构数据库进行了与每个原发部位生存相关的预后因素和治疗的多变量分析。使用显著因素来定义更新的 GPA。GPA 为 4.0 和 0.0 分别与最佳和最差预后相关。
诊断相关的显著预后因素各不相同，并且确定了新的预后因素。这些因素被纳入更新的 GPA 中，亚组之间具有明显的分离（<0.01）。尽管生存情况有所改善，但对于患有非小细胞肺癌、乳腺癌、黑色素瘤、胃肠道和肾癌的脑转移患者，生存情况仍有很大差异，分别为 7-47 个月、3-36 个月、5-34 个月、3-17 个月和 4-35 个月。
中位生存时间差异很大，我们估计脑转移患者生存的能力有所提高。更新的 GPA（可在 brainmetgpa.com 上免费获得）提供了一种准确的工具，可以估计生存情况、个体化治疗和分层临床试验。不应该排除脑转移患者，应该鼓励他们参加临床试验，并根据 GPA 对这些试验进行分层，以确保这些试验进行适当的比较。此外，我们建议扩大资格范围，以允许纳入有 50%或更高概率再生存一年的（资格系数>0.50）的既往脑转移患者。
