Kim Joseph M, Miller Jacob A, Kotecha Rupesh, Xiao Roy, Juloori Aditya, Ward Matthew C, Ahluwalia Manmeet S, Mohammadi Alireza M, Peereboom David M, Murphy Erin S, Suh John H, Barnett Gene H, Vogelbaum Michael A, Angelov Lilyana, Stevens Glen H, Chao Samuel T
School of Medicine, Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA.
Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.
J Neurooncol. 2017 Jun;133(2):357-368. doi: 10.1007/s11060-017-2442-8. Epub 2017 Apr 22.
To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.
目的在于研究新诊断的脑转移瘤患者在接受立体定向放射外科治疗（SRS）时联合或不联合全脑放疗（WBRT）及全身治疗后的晚期毒性反应。1997年至2015年期间在一家三级医疗机构接受SRS治疗的新诊断脑转移瘤患者符合纳入标准。收集每位患者所有全身治疗的类型和时间。主要结局指标为影像学放射性坏死（RN）的累积发生率。采用多变量竞争风险回归分析来调整混杂因素。在研究期间，1650例患者出现2843个颅内转移瘤。其中，445例患者（27%）接受了SRS及全身联合治疗。治疗后222个（8%）病灶出现影像学RN，其中120个（54%）有症状。接受和未接受联合治疗的病灶12个月RN累积发生率分别为6.6%和5.3%（p = 0.14）。在接受 upfront SRS和WBRT治疗的病灶中，联合全身治疗与RN发生率显著增加相关（8.7%对3.7%，p = 0.04）。特别是，联合靶向治疗显著增加了12个月RN累积发生率（8.8%对5.3%，p < 0.01）。在这些治疗中，观察到血管内皮生长因子受体（VEGFR）酪氨酸激酶抑制剂（TKIs）（14.3%对6.6%，p = 0.04）和表皮生长因子受体（EGFR）TKIs（15.6%对6.0%，p = 0.04）使RN发生率显著增加。大多数类型的全身治疗在新诊断脑转移瘤的治疗中可与SRS安全联合应用。然而，在SRS和WBRT基础上加用联合全身治疗会使影像学RN发生率显著增加。
