Abstract

Background

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.

Methods

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).

Results

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.

Conclusion

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.

中文翻译：

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质子颅脊髓照射治疗软脑膜转移瘤的临床试验

 抽象的

 背景

软脑膜转移（LM）与有限的生存和治疗选择相关。虽然累及野放疗对局部姑息治疗有效，但缺乏持久性。我们评估了质子颅脊髓照射 (CSI) 对实体瘤 LM 患者的毒性，这是一种涵盖整个中枢神经系统 (CNS) 区室的治疗方法。

 方法

在这项 I 期前瞻性试验中，我们招募了 LM 患者接受大分割质子 CSI。主要终点是描述治疗相关毒性，剂量限制毒性 (DLT) 定义为根据治疗期间或期间发生的不良事件通用术语标准的任何与辐射相关的 3 级非血液毒性或 4 级血液毒性。质子 CSI 完成 4 周。次要终点包括中枢神经系统无进展生存期（PFS）和总生存期（OS）。

 结果

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。剂量扩展队列中的两名患者经历了 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 均在无需医疗干预的情况下得到解决。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%) 的中枢神经系统无进展超过 12 个月。

 结论

使用质子治疗的大分割质子 CSI 对于实体​​瘤 LM 患者来说是一种安全的治疗方法。我们看到一些患者的疾病得到了持久的控制。