质子颅脊髓照射治疗软脑膜转移患者：一项随机临床试验。
Proton Craniospinal Irradiation for Patients With Leptomeningeal Metastasis: A Randomized Clinical Trial.
作者信息
Yang Jonathan T, Yerramilli Divya, Pentsova Elena, Wolden Suzanne, Young Robert J, Correa Denise D, Imber Brandon S, Wijetunga N Ari, Goglia Alexander G, Zhang Zhigang, Zheng Junting, Baser Raymond, Bernstein Ashley, Kratochvil Leah, Xiao Julie, Hattangadi-Gluth Jona, Miller Alexandra M, Wilcox Jessica A, Betof Warner Allison, Yu Helena, Kris Mark G, Seidman Andrew D, Powell Simon N, Boire Adrienne
机构信息
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Radiation Oncology, New York University Grossman School of Medicine, New York, New York.
出版信息
JAMA Oncol. 2025 Sep 4. doi: 10.1001/jamaoncol.2025.3007.
IMPORTANCE
Leptomeningeal metastasis (LM) is associated with limited survival and few treatment options. Photon involved-field radiotherapy (IFRT) is the most common radiotherapy treatment for patients with LM from solid tumors.
OBJECTIVE
To assess whether proton craniospinal irradiation (pCSI) would result in superior central nervous system progression-free survival (CNS-PFS) compared with IFRT.
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. Patients with other solid tumors were also enrolled in an exploratory pCSI cohort.
INTERVENTION
For the randomized groups, after stratifying by histology and systemic disease status, patients were assigned (2:1) to pCSI or IFRT.
MAIN OUTCOMES AND MEASURES
The primary end point was CNS-PFS. Secondary end points included overall survival (OS).
RESULTS
Of 98 total patients, 72 individuals (73.5%) were female, and the median (IQR) age was 59 (50-65) years. A total of 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively. 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). 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. 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).
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. The results suggest that pCSI should be considered when available.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04343573.
重要性
软脑膜转移（LM）与生存期有限及治疗选择较少相关。光子累及野放疗（IFRT）是实体瘤所致LM患者最常用的放疗治疗方法。
目的
评估质子全脑全脊髓照射（pCSI）与IFRT相比是否能带来更优的中枢神经系统无进展生存期（CNS-PFS）。
设计、设置和参与者：于2020年4月16日至2021年10月11日进行了一项pCSI与IFRT对比的随机2期试验，纳入了患有LM的非小细胞肺癌和乳腺癌患者。其他实体瘤患者也被纳入一个探索性pCSI队列。
干预措施
对于随机分组的各组，在按组织学和全身疾病状态分层后，患者按2:1分配至pCSI组或IFRT组。
主要结局和测量指标
主要终点为CNS-PFS。次要终点包括总生存期（OS）。
结果
在总共98例患者中，72例（73.5%）为女性，中位（IQR）年龄为59（50 - 65）岁。分别有42例和21例患者被随机分配至pCSI组和IFRT组。在计划中的中期分析时，观察到pCSI组与IFRT组相比在CNS-PFS方面有显著益处，导致试验提前终止。在本次最终分析中，持续观察到pCSI组在CNS-PFS方面有显著益处（中位值8.2个月；95%CI，6.6 - 15.3），而IFRT组为（中位值2.3个月；95%CI，1.2 - 4.0；P < 0.001）。还观察到pCSI组在OS方面有统计学显著且具有临床意义的益处（中位值11.3个月；95%CI，7.5 - 18.3），而IFRT组为（中位值4.9个月；95%CI，3.9 - 15.0；P = 0.04）。对于探索性pCSI队列（n = 35），中位CNS-PFS为5.8个月（95%CI，4.4 - 9.1），OS为7.0个月（95%CI，5.4 - 10.6）。
结论和相关性
这项评估LM最佳放疗治疗方法的随机临床试验发现，与IFRT相比，pCSI可改善CNS-PFS和OS。结果表明，如有条件应考虑使用pCSI。
试验注册
ClinicalTrials.gov标识符：NCT04343573。
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