Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
PROMISE (Precision Radiation for OligoMetastatIc and MetaStatic DiseasE) Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Neuro Oncol. 2021 Jan 30;23(1):134-143. doi: 10.1093/neuonc/noaa152.
Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors.
We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS).
We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months.
Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.
脑膜转移（LM）与有限的生存和治疗选择相关。虽然受累野放疗对局部缓解有效，但缺乏持久性。我们评估了质子颅脑脊柱照射（CSI）的毒性，这是一种涵盖整个中枢神经系统（CNS）区域的治疗方法，用于治疗来自实体瘤的 LM 患者。
我们招募了 LM 患者接受分次质子 CSI 的这项 I 期前瞻性试验。主要终点是描述与治疗相关的毒性，根据不良事件常用术语标准，根据不良事件常用术语标准，剂量限制毒性（DLT）定义为质子 CSI 期间或完成后 4 周内发生的任何与放射相关的 3 级非血液学毒性或 4 级血液学毒性。次要终点包括 CNS 无进展生存期（PFS）和总生存期（OS）。
我们在 2018 年 6 月至 2019 年 4 月期间招募了 24 名患者。他们的中位随访时间为 11 个月。20 名患者可评估方案治疗相关毒性，21 名患者可评估 CNS PFS 和 OS。剂量扩展队列中的 2 名患者发生 DLT，包括 4 级淋巴细胞减少症、4 级血小板减少症和/或 3 级疲劳。所有 DLT 均无需医疗干预而解决。中位 CNS PFS 为 7 个月（95%CI：5-13），中位 OS 为 8 个月（95%CI：6 至未达到）。4 名患者（19%）在 CNS 中无疾病进展超过 12 个月。
使用质子治疗的分次质子 CSI 是治疗来自实体瘤的 LM 患者的一种安全治疗方法。我们在一些患者中看到了持久的疾病控制。
