新诊断的原发性中枢神经系统淋巴瘤(PCNSL)的治疗包括给予基于大剂量甲氨蝶呤的方案,然后进行巩固治疗,以最大程度地降低复发风险。然而,最佳巩固策略(自体造血细胞移植[auto-HCT]与全脑放疗[WBRT])是有争议的。因此,我们对所有随机对照试验进行了系统评价和荟萃分析,比较了一线治疗后PCNSL患者的auto-HCT与WBRT巩固治疗.主要结果是总生存期(OS),而次要结局包括无进展生存期(PFS),缓解率(总体缓解率[ORR]和完全缓解率[CR]),复发率,治疗相关死亡率(TRM),和神经心理学不良事件。我们对纳入自动HCT或WBRT巩固的单臂研究进行了汇总分析,并评估了神经认知结果。只有两项研究符合纳入标准(n=240)。OS差异无统计学意义(HR=1.50;95%CI=0.95-2.36),PFS(HR=0.99;95%CI=0.44-2.22),ORR(RR=1.48;95%CI=0.90-2.44),CR率(RR=1.21;95%CI=0.90-1.63),复发率(RR=0.46;95%CI=0.05-4.28),和TRM(RR=5.67;95%CI=1.01-31.91)。在两项研究中,用于评估神经认知领域的神经心理学测试是不同的,并且报告不一致,因此我们无法进行荟萃分析,但提供了描述性评估。两项研究均显示,与自动HCT相比,接受WBRT的人的注意力/执行功能(基于跟踪测试A和跟踪测试B)显着下降。我们发现了9项单臂II期研究,报告了与自动HCT(5项研究)或WBRT(4项研究)合并相关的结果数据。其中,两项研究(n=43)报道了自动HCT巩固后神经认知功能下降的数据。在这些研究中,接受auto-HCT的神经认知能力下降患者的合并比例为6%(95%CI,0%-17%),并且研究之间没有异质性(I2=0%)。三项研究(n=122)报道了WBRT巩固后神经认知能力下降的数据。在这些研究中,接受WBRT的神经认知能力下降患者的合并比例为43%(95%CI,11%-78%),并且研究之间存在高度异质性(I2=94%)。亚组之间存在显著异质性(p=0.035)。接受自动HCT或WBRT巩固治疗的PCNSL患者的结果没有显着差异。然而,与自动HCT巩固相比,与WBRT相关的神经认知能力下降程度更高.选择整合策略的决定需要根据年龄进行个性化,脆弱,和合并症。
The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high-dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto-HCT] vs. whole-brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic
review and meta-analysis of all randomized controlled trials that compared auto-HCT versus WBRT consolidation for patients with PCNSL after first-line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment-related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single-arm studies that incorporated auto-HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95-2.36), PFS (HR = 0.99; 95% CI = 0.44-2.22), ORR (RR = 1.48; 95% CI = 0.90-2.44), CR rate (RR = 1.21; 95% CI = 0.90-1.63), relapse rate (RR = 0.46; 95% CI = 0.05-4.28), and TRM (RR = 5.67; 95% CI = 1.01-31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta-analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto-HCT. We found 9 single-arm phase II studies that reported data on outcomes associated with either auto-HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto-HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%-17%) for those receiving auto-HCT and there was no heterogeneity between studies (I2 = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%-78%) for those receiving WBRT and there was high heterogeneity between studies (I2 = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto-HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto-HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co-morbidities.