Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA.
Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Breast Cancer Res Treat. 2019 Jun;175(3):781-788. doi: 10.1007/s10549-019-05170-7. Epub 2019 Mar 11.
Leptomeningeal disease is a rare presentation of advanced metastatic breast cancer. The purpose of this study was to evaluate craniospinal progression between intrathecal (IT) trastuzumab, IT chemotherapy, and whole brain radiation therapy (WBRT) in leptomeningeal disease.
A total of 56 patients were identified with breast cancer leptomeningeal disease at our institution treated with IT trastuzumab (n = 18; 32%), single-agent IT chemotherapy (methotrexate n = 14 or thiotepa n = 1; 27%), or WBRT alone (n = 23; 41%). Patients were treated beginning November 2012 and followed until November 2018.
Median time from breast cancer diagnosis to development of leptomeningeal disease was 4.3 years. There were no significant differences noted between IT trastuzumab, IT chemotherapy, or WBRT groups in age (p = 0.4), Karnofsky Performance Status (KPS) (p = 0.07), or receipt of systemic therapy at time of leptomeningeal disease treatment (p = 0.47). Median follow-up of patients from leptomeningeal diagnosis was 5 months (range 0.2-81.1 months). Significant differences were noted in Kaplan-Meier (KM) craniospinal progression-free survival (CS-PFS) with 6-month rates of 44%, 18%, and 26% (p = 0.04) between IT trastuzumab, IT chemotherapy, and WBRT, respectively. Craniospinal control > 10 months was achieved in four patients treated with IT trastuzumab. Twelve-month KM OS rates were 54%, 10%, and 19% (p = 0.01) between IT trastuzumab, IT chemotherapy, and WBRT groups, respectively. IT therapy was adequately tolerated with three patients undergoing treatment-related hospitalizations.
In our institutional series, significant differences were noted in CS-PFS and OS by treatment modality. IT trastuzumab should be considered in the management HER2+ breast leptomeningeal disease.
脑膜疾病是晚期转移性乳腺癌的一种罕见表现。本研究旨在评估脑膜疾病中鞘内（IT）曲妥珠单抗、IT 化疗和全脑放疗（WBRT）之间的颅脊髓进展情况。
本研究共纳入 56 例在我院接受 IT 曲妥珠单抗（n=18；32%）、单药 IT 化疗（甲氨蝶呤 n=14 或噻替派 n=1；27%）或单独 WBRT（n=23；41%）治疗的乳腺癌脑膜疾病患者。患者于 2012 年 11 月开始接受治疗，并随访至 2018 年 11 月。
从乳腺癌诊断到脑膜疾病发展的中位时间为 4.3 年。在 IT 曲妥珠单抗、IT 化疗或 WBRT 组之间，年龄（p=0.4）、卡氏功能状态评分（KPS）（p=0.07）或脑膜疾病治疗时全身治疗的接受情况（p=0.47）均无显著差异。脑膜疾病诊断后患者的中位随访时间为 5 个月（范围 0.2-81.1 个月）。Kaplan-Meier（KM）颅脊髓无进展生存期（CS-PFS）有显著差异，6 个月时的累积无进展生存率分别为 44%、18%和 26%（p=0.04）。接受 IT 曲妥珠单抗治疗的患者中，有 4 例颅脊髓控制>10 个月。12 个月时的 KM 总生存率分别为 54%、10%和 19%（p=0.01）。IT 治疗的耐受性良好，有 3 例患者因治疗相关住院。
在本机构系列中，不同治疗方式的 CS-PFS 和 OS 存在显著差异。在 HER2+乳腺癌脑膜疾病的治疗中，应考虑使用 IT 曲妥珠单抗。
