Adib Elio, Nassar Amin H, Bou Farhat Elias, Tanguturi Shyam K, Rahman Rifaquat M, Haas-Kogan Daphne A, Bi Wenya Linda, Arnaout Omar, Wen Patrick Y, Kwiatkowski David J, Awad Mark M, Aizer Ayal A
Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Medical Oncology, Yale New-Haven Cancer Center, New Haven, Connecticut.
JTO Clin Res Rep. 2025 Jan 17;6(4):100797. doi: 10.1016/j.jtocrr.2025.100797. eCollection 2025 Apr.
Patients with NSCLC and brain metastases have a poor prognosis. Combining brain-directed radiation therapy (RT) with immune checkpoint inhibitors (ICIs) may be synergistic. Nevertheless, predictors of response and toxicity are lacking.
This retrospective study conducted at Dana-Farber Brigham Cancer Center from 2015 to 2023 included patients with non- and non--altered NSCLC and newly diagnosed brain metastases starting ICI within 90 days of brain-directed RT. We assessed all-cause mortality, systemic and neurologic death, systemic and intracranial progression at the patient level, and local recurrence and radiation necrosis at the metastasis level.
Among the 178 patients with 536 brain metastases, the median age was 64 years, and 53% were female individuals. The median number of brain metastases detected at diagnosis was three. Most patients received pembrolizumab (93%) and were treated with stereotactic radiation (81%). Higher programmed death-ligand 1 (PD-L1) expression was associated with improved all-cause mortality (median survival: PD-L1 less than 1%: 10.7 mo, 1%-49%: 14.3 mo, more or equal to 50%: 29.5 mo), driven by longer time to systemic death. Higher PD-L1 was also associated with improved systemic progression-free survival ( = 0.02) and distant intracranial disease-free survival ( = 0.02). The rate of local recurrence was low across all groups (1%-4% at 2 y). Patients with higher PD-L1 had numerically higher radiographic radiation necrosis rates (2.3%, 5.5%, 9.3% at 2 y for PD-L1 <1%, 1%-49%, and ≥50%, respectively, = 0.08) and significantly higher symptomatic radiation necrosis rates ( = 0.04).
The combination of brain-directed RT and ICI is effective in treating patients with NSCLC and brain metastases. Although high PD-L1 levels are associated with longer survival and improved intracranial control, radiation necrosis occurs more frequently in patients with high PD-L1 expression. Clinicians should be aware of long-term treatment-related toxicities in this population.
非小细胞肺癌（NSCLC）合并脑转移患者的预后较差。将脑定向放射治疗（RT）与免疫检查点抑制剂（ICI）联合使用可能具有协同作用。然而，目前缺乏疗效和毒性的预测指标。
这项回顾性研究于2015年至2023年在丹娜法伯布列根和妇女癌症中心进行，纳入了非小细胞肺癌且无特定基因改变、新诊断为脑转移并在脑定向放疗90天内开始使用ICI的患者。我们在患者层面评估了全因死亡率、全身和神经系统死亡、全身和颅内进展情况，以及在转移灶层面评估了局部复发和放射性坏死情况。
在178例有536个脑转移灶的患者中，中位年龄为64岁，53%为女性。诊断时检测到的脑转移灶中位数为3个。大多数患者接受派姆单抗治疗（93%），并接受了立体定向放射治疗（81%）。更高的程序性死亡配体1（PD-L1）表达与全因死亡率改善相关（中位生存期：PD-L1低于1%：10.7个月，1%-49%：14.3个月，≥50%：29.5个月），这是由更长的全身死亡时间驱动的。更高的PD-L1水平还与全身无进展生存期改善（P = 0.02）和远处颅内无病生存期改善（P = 0.02）相关。所有组的局部复发率都很低（2年时为1%-4%）。PD-L1水平较高的患者影像学放射性坏死率在数值上更高（PD-L1<1%、1%-49%和≥50%在2年时分别为2.3%、5.5%和9.3%，P = 0.08），有症状的放射性坏死率显著更高（P = 0.04）。
脑定向放疗与ICI联合治疗NSCLC合并脑转移患者有效。虽然高PD-L1水平与更长生存期和更好的颅内控制相关，但高PD-L1表达的患者放射性坏死更频繁发生。临床医生应意识到该人群长期的治疗相关毒性。
