Proton Craniospinal Irradiation for Patients With Leptomeningeal Metastasis: A Randomized Clinical Trial.

Photon involved-field radiotherapy (IFRT) is the most common radiotherapy treatment for patients with LM from solid tumors.

光子涉及野放疗（IFRT）是治疗实体瘤患者脑膜下转移（LM）最常用的放疗方法。

Background

To assess whether proton craniospinal irradiation (pCSI) would result in superior central nervous system progression-free survival(CNS-PFS) compared with IFRT.

评估质子颅脊髓放疗（pCSI）是否能与全身放疗（IFRT）相比，带来更优越的中枢神经系统无进展生存（CNS-PFS）。

DESIGN, SETTING, AND PARTICIPANTS: A randomized, phase 2 trial of pCSI vs IFRT was conducted between April 16, 2020, and October 11, 2021, and included patients with non-small cell lung cancer and breast cancer with LM.

设计、环境和参与者：2020年4月16日至2021年10月11日进行了一项pCSI与IFRT的随机、II期试验，包括非小细胞肺癌和有脑转移的乳腺癌患者。

Patients with other solid tumors were also enrolled in an exploratory pCSI cohort.

其他实体瘤患者也被纳入了探索性 pCSI 队列。

intervention

For the randomized groups, after stratifying by histology and systemic disease status, patients were assigned (2:1) to pCSI or IFRT.

对于随机分组的患者，在按组织学和系统性疾病状态分层后，按2:1的比例分配至 pCSI 或 IFRT。

main_outcomes_and_measures

The primary end point was CNS-PFS.

主要终点是中枢神经系统无进展生存期(CNS-PFS)。

Secondary end points included overall survival(OS).

次要终点包括总生存(OS)。

Results

Of 98 total patients, 72 individuals (73.5%) were female, and the median (IQR) age was 59 (50-65) years.

在98名患者中，有72名（73.5%）为女性，年龄中位数（四分位数间距）为59（50-65）岁。

A total of 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively.

共有42名和21名患者分别随机分配至pCSI和IFRT治疗组。

At planned interim analysis, a significant benefit in CNS-PFS was observed with pCSI compared with IFRT, leading to the early discontinuation of the trial. In this final analysis, a significant benefit was continually observed in CNS-PFS with pCSI (median, 8.2 months; 95% CI, 6.6-15.3) vs IFRT (median, 2.3 months; 95% CI, 1.2-4.0; P < .001).

在计划的中期分析中，与IFRT相比，pCSI在中枢神经系统无进展生存期（CNS-PFS）上显示出显著的益处，导致试验提前终止。在这次最终分析中，与IFRT相比，pCSI在CNS-PFS上仍然显示出显著的益处（中位生存期，8.2个月；95%置信区间，6.6-15.3）vs IFRT（中位生存期，2.3个月；95%置信区间，1.2-4.0；P < .001）。

A statistically significant and clinically meaningful OS benefit with pCSI (median, 11.3 months; 95% CI, 7.5-18.3) vs IFRT (median, 4.9 months; 95% CI, 3.9-15.0; P = .04) was also observed.

与IFRT相比，pCSI在总生存（OS）上也显示出统计学上显著且具有临床意义的益处（中位生存期，11.3个月；95%置信区间，7.5-18.3）vs IFRT（中位生存期，4.9个月；95%置信区间，3.9-15.0；P = .04）。

For the exploratory pCSI cohort (n = 35), the median CNS-PFS was 5.8 months (95% CI, 4.4-9.1) and OS was 7.0 months (95% CI, 5.4-10.6).

在探索性 pCSI 队列（n = 35）中，中位中枢神经系统无进展生存期（CNS-PFS）为5.8个月（95% 置信区间，4.4-9.1），总生存期（OS）为7.0个月（95% 置信区间，5.4-10.6）。

conclusions_and_relevance

This randomized clinical trial that assessed the optimal radiotherapy treatment for LM found improved CNS-PFS and OS with pCSI compared with IFRT.

这项评估 LM 最佳放射治疗的随机临床试验发现，与 IFRT 相比，pCSI 改善了中枢神经系统无进展生存期（CNS-PFS）和总生存期（OS）。

The results suggest that pCSI should be considered when available.

结果表明，应考虑在可行的情况下使用pCSI。

trial_registration

ClinicalTrials.gov Identifier: NCT04343573.

ClinicalTrials.gov注册号：NCT04343573。