Dutta Sunil W, Mack Marie L, Aliotta Eric, Ward Kristin A, Muller Donald A, Larner James M, Fadul Camilo E, Hall Richard D, Gentzler Ryan D, Sheehan Jason P
Department of Radiation Oncology, University of Virginia, PO Box 800383, Charlottesville, VA, 22908, USA.
Department of Neurology, University of Virginia, Charlottesville, VA, USA.
J Neurooncol. 2020 Sep;149(2):357-366. doi: 10.1007/s11060-020-03615-4. Epub 2020 Sep 9.
PURPOSE/OBJECTIVE(S): Tyrosine kinase inhibitors (TKIs) are commonly employed for patients with brain metastases from lung cancer and specific driver mutations. We sought to identify the correlation between intracranial tumor burden and outcomes in patients with brain metastases treated with TKIs.
MATERIALS/METHODS: We identified and retrospectively reviewed cases of EGFR-mutant or ALK-rearranged lung cancer with brain metastases at any time during their cancer course. Clinical characteristics and treatment information were abstracted from the medical records. Brain metastases were contoured to calculate total volume of disease at diagnosis and after initial therapy. High intracranial burden was defined as either > 10 brain metastases, volume of brain metastases > 15 cc, or largest lesion > 3 cm. Intracranial response was determined according to Response Assessment in Neuro-Oncology (RANO) criteria on the patient level. We determined the correlation between clinical and imaging characteristics and intracranial progression free survival (IC-PFS) and overall survival (OS).
Fifty-seven patients with EGFR (n = 49) and ALK (n = 8) alterations were identified. Median follow-up from initial brain metastasis diagnosis was 17 months. Neurological symptoms were present in 54% at brain metastasis diagnosis. For those receiving TKIs alone or TKIs with radiation, at least a partial intracranial response (≥ 65% volume reduction) at 3 months from starting therapy was achieved in 94% and 58%. Progressive intracranial disease at 3 months occurred in 6.3% and 8.3%. Patients with high intracranial burden (n = 21) had a median 17 brain metastases, 6.5 cc volume, and 1.9 cm maximal tumor diameter. Median IC-PFS and OS for patients with high intracranial burden was 13.9 and 35.4 months. Patients with high intracranial burden and neurological symptoms at diagnosis had similar IC-PFS and OS compared to those with low burden and absence of neurological symptoms (p > 0.05 for each).
Most patients receiving TKIs as part of their initial therapy achieve an early and durable volumetric intracranial response, irrespective of presenting disease burden or neurologic symptoms.
酪氨酸激酶抑制剂（TKIs）常用于患有肺癌脑转移且具有特定驱动基因突变的患者。我们试图确定接受TKIs治疗的脑转移患者的颅内肿瘤负荷与预后之间的相关性。
我们识别并回顾性分析了在癌症病程中任何时间发生脑转移的EGFR突变或ALK重排肺癌病例。从病历中提取临床特征和治疗信息。对脑转移灶进行轮廓勾画，以计算诊断时和初始治疗后的疾病总体积。高颅内负荷定义为脑转移灶>10个、脑转移灶体积>15立方厘米或最大病灶>3厘米。根据神经肿瘤学反应评估（RANO）标准在患者层面确定颅内反应。我们确定了临床和影像学特征与颅内无进展生存期（IC-PFS）和总生存期（OS）之间的相关性。
共识别出57例EGFR（n = 49）和ALK（n = 8）改变的患者。从最初诊断脑转移起的中位随访时间为17个月。脑转移诊断时54%的患者存在神经症状。对于单独接受TKIs或接受TKIs联合放疗的患者，开始治疗3个月时至少达到部分颅内反应（体积减少≥65%）的比例分别为94%和58%。3个月时颅内疾病进展的比例分别为6.3%和8.3%。高颅内负荷患者（n = 21）的脑转移灶中位数为17个，体积为6.5立方厘米，最大肿瘤直径为1.9厘米。高颅内负荷患者的中位IC-PFS和OS分别为13.9个月和35.4个月。诊断时高颅内负荷且有神经症状的患者与低负荷且无神经症状的患者相比，IC-PFS和OS相似（每项p>0.05）。
大多数接受TKIs作为初始治疗一部分的患者，无论初始疾病负荷或神经症状如何，都能实现早期且持久的颅内体积反应。
