Wijetunga N Ari, Boire Adrienne, Young Robert J, Yamada Yoshiya, Wolden Suzanne, Yu Helena, Kris Mark, Seidman Andrew, Betof-Warner Allison, Diaz Maria, Reiner Anne, Malani Rachna, Pentsova Elena, Yang Jonathan T
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Neurooncol Adv. 2021 Dec 4;3(1):vdab181. doi: 10.1093/noajnl/vdab181. eCollection 2021 Jan-Dec.
Leptomeningeal metastasis (LM) involves cerebrospinal fluid (CSF) seeding of tumor cells. Proton craniospinal irradiation (pCSI) is potentially effective for solid tumor LM. We evaluated whether circulating tumor cells (CTCs) in the CSF (CTC), blood (CTC), and neuroimaging correlate with outcomes after pCSI for LM.
We describe a single-institution consecutive case series of 58 patients treated with pCSI for LM. Pre-pCSI CTCs, the change in CTC post-pCSI (Δ ), and MRIs were examined. Central nervous system progression-free survival (CNS-PFS) and overall survival (OS) from pCSI were determined using Kaplan Meier analysis, Cox proportional-hazards regression, time-dependent ROC analysis, and joint modeling of time-varying effects and survival outcomes.
The median CNS-PFS and OS were 6 months (IQR: 4-9) and 8 months (IQR: 5-13), respectively. Pre-pCSI CTC < 53/3mL was associated with improved CNS-PFS (12.0 vs 6.0 months, < .01). Parenchymal brain metastases ( = 34, 59%) on pre-pCSI MRI showed worse OS (7.0 vs 13 months, = .01). Through joint modeling, CTC was significantly prognostic of CNS-PFS ( < .01) and OS ( < .01). A Δ ≥37 cells/3mL, the median Δ at nadir, showed improved CNS-PFS (8.0 vs 5.0 months, = .02) and further stratified patients into favorable and unfavorable subgroups (CNS-PFS 8.0 vs 4.0 months, < .01). No associations with CTC were found.
We found the best survival observed in patients with low pre-pCSI CTC and intermediate outcomes for patients with high pre-pCSI CTC but large Δ . These results favor additional studies incorporating pCSI and CTC measurement earlier in the LM treatment paradigm.
软脑膜转移（LM）涉及肿瘤细胞在脑脊液（CSF）中的播散。质子颅脊柱照射（pCSI）对实体瘤LM可能有效。我们评估了脑脊液中的循环肿瘤细胞（CSF-CTC）、血液中的循环肿瘤细胞（CTC）以及神经影像学检查结果与pCSI治疗LM后的预后是否相关。
我们描述了一个单机构连续病例系列，共58例接受pCSI治疗LM的患者。对pCSI治疗前的CSF-CTC、pCSI治疗后CSF-CTC的变化（Δ）以及MRI进行了检查。使用Kaplan-Meier分析、Cox比例风险回归、时间依赖性ROC分析以及时变效应和生存结局的联合模型，确定了pCSI治疗后的中枢神经系统无进展生存期（CNS-PFS）和总生存期（OS）。
中位CNS-PFS和OS分别为6个月（IQR：4-9）和8个月（IQR：5-13）。pCSI治疗前CSF-CTC<53/3mL与改善的CNS-PFS相关（12.0对6.0个月，P<.01）。pCSI治疗前MRI显示的脑实质转移瘤（n=34，59%）的OS较差（7.0对13个月，P=.01）。通过联合模型，CSF-CTC对CNS-PFS（P<.01）和OS（P<.01）具有显著的预后价值。Δ≥37个细胞/3mL（最低点时的中位Δ）显示出改善的CNS-PFS（8.0对5.0个月，P=.02），并进一步将患者分为预后良好和不良亚组（CNS-PFS 8.0对4.0个月，P<.01）。未发现与血液中CTC相关的关联。
我们发现pCSI治疗前CSF-CTC水平低的患者生存期最佳，而pCSI治疗前CSF-CTC水平高但Δ大的患者预后中等。这些结果支持在LM治疗模式中更早地纳入pCSI和CSF-CTC测量的进一步研究。
