Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60153, USA.
J Neurooncol. 2019 Jun;143(2):337-347. doi: 10.1007/s11060-019-03169-0. Epub 2019 Apr 13.
Stereotactic radiosurgery (SRS) can enhance immune activation and improve disease control through stimulation of anti-tumor immunity. However, patients with cancer receiving chemotherapy are often immunosuppressed, which may impact the efficacy of SRS. Here we investigate the relationship between systemic lymphopenia and response to SRS in patients with brain-metastatic lung cancer.
We reviewed 125 patients with lung cancer brain metastases treated with SRS between January 2014 and May 2017. Complete blood counts from the time of SRS were reviewed, and lymphopenia was defined as absolute lymphocyte count < 1×10 cells/L. Kaplan-Meier survival analysis and cox proportional-hazards models were used to evaluate risks of progression and death.
The median age was 65 years (range 43-86), with 54% female patients. Lymphopenia was present in 60 patients. In univariate analysis, lymphopenic patients had significantly shorter PFS (HR = 2.995, p < 0.0001) and OS (HR = 3.928, p < 0.0001). When accounting for age, gender, smoking history, ECOG score, surgery, and tumor histology in a multivariate model, lymphopenia remained significantly predictive of worse PFS (HR = 1.912, p = 0.002) and OS (HR = 2.257, p < 0.001). Patients who received immunotherapy within 3 months of SRS demonstrated significantly shorter PFS (HR = 3.578, p = 0.006) and OS (HR = 6.409, p = 0.001) if lymphopenic.
Brain-metastatic lung cancer patients with lymphopenia treated with SRS had significantly worse PFS and OS. The effect of lymphopenia was even more pronounced in patients receiving immunotherapy. These data demonstrate the significant impact of deficient immunity on disease control and survival. Lymphopenic patients may benefit from interventions to improve immune function prior to SRS for brain metastases.
立体定向放射外科（SRS）可以通过刺激抗肿瘤免疫来增强免疫激活并改善疾病控制。然而，接受化疗的癌症患者通常会出现免疫抑制，这可能会影响 SRS 的疗效。在这里，我们研究了全身淋巴细胞减少与肺癌脑转移患者 SRS 反应之间的关系。
我们回顾了 2014 年 1 月至 2017 年 5 月期间接受 SRS 治疗的 125 例肺癌脑转移患者。回顾 SRS 时的全血细胞计数，将淋巴细胞减少定义为绝对淋巴细胞计数<1×10 个细胞/L。使用 Kaplan-Meier 生存分析和 Cox 比例风险模型评估进展和死亡的风险。
中位年龄为 65 岁（范围 43-86 岁），女性占 54%。60 例患者存在淋巴细胞减少。在单因素分析中，淋巴细胞减少的患者 PFS（风险比[HR] = 2.995，p<0.0001）和 OS（HR = 3.928，p<0.0001）明显更短。当在多变量模型中考虑年龄、性别、吸烟史、ECOG 评分、手术和肿瘤组织学时，淋巴细胞减少仍然是 PFS（HR = 1.912，p = 0.002）和 OS（HR = 2.257，p<0.001）较差的显著预测因素。在 SRS 后 3 个月内接受免疫治疗的患者，如果淋巴细胞减少，PFS（HR = 3.578，p = 0.006）和 OS（HR = 6.409，p = 0.001）明显更短。
接受 SRS 治疗的肺癌脑转移伴淋巴细胞减少的患者 PFS 和 OS 明显更差。淋巴细胞减少对接受免疫治疗的患者的影响更为明显。这些数据表明，免疫缺陷对疾病控制和生存有显著影响。淋巴细胞减少的患者可能受益于在 SRS 治疗脑转移之前改善免疫功能的干预措施。
