Ryu Hyejo, Li Xue, Lee Tae Hoon, Kim Tae Min, Choi Seung Hong, Park Chul-Kee, Lee Soon Tae, Park Sung-Hye, Won Jae-Kyung, Jang Bum-Sup, Kim Il Han, Lee Joo Ho
Department of Radiation Oncology, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Gyeonggii-Do, Republic of Korea.
Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea.
J Neurooncol. 2025 May;173(1):95-104. doi: 10.1007/s11060-025-04965-7. Epub 2025 Feb 19.
Hippocampal injury from WBRT contributes to neurocognitive decline in brain malignancy patients. HA-WBRT may mitigate this by reducing hippocampal radiation exposure, but its feasibility in PCNSL remains unassessed regarding hippocampal involvement and failure rates. This study evaluates hippocampal involvement at diagnosis and after treatment in PCNSL patients.
We conducted a retrospective analysis of 278 immunocompetent PCNSL patients diagnosed between 2000 and 2021. Following high-dose methotrexate-based induction chemotherapy, patients either received consolidation therapy, including RT, cytarabine alone, or autologous stem cell transplantation or underwent observation. Hippocampus was outlined on T1 MRI images and expanded by a 5 mm margin to create the hippocampal avoidance region (HAR). Hippocampal failure was defined as recurrence or progression at HAR. The median follow-up was 38.7 months (range 3.1-239.4 months).
Of the 278 patients diagnosed with PCNSL, 39.9% presented initial lesions at HAR. After induction therapy, 212 evaluable patients received consolidation treatments or observation. Intracranial failures occurred in 47.6% (n = 101), with 66.3% (n = 67) occurring outside the HAR and 33.7% (n = 34) inside the HAR. Unifocal disease (HR 0.61, 95% CI 0.39-0.96, p = 0.025) was associated with a lower risk of hippocampal failures, while initial HAR involvement significantly increased the risk (HR 2.26, 95% CI 1.18-4.47, p = 0.018). Patients with unifocal disease outside the HAR had the lowest 3-year hippocampal failure rate (6.2%). RT that included the hippocampus did not significantly affect hippocampal failure rates in patients without initial HAR lesions (p = 0.282), with three-year rates of 9.2 vs. 14.6% for other treatments. However, among patients with initial HAR involvement, RT including the hippocampus significantly reduced hippocampal failure rates compared to other approaches (p = 0.002). Hippocampal failure rates were comparable, with conventional WBRT at 14.6% and HA-WBRT at 19% in patients without initial HAR lesions (p = 0.734).
The routine application of the HA-WBRT strategy is not supported due to the high risk of hippocampal failures in general and requires further investigation to establish its feasibility and safety in well-defined subgroups. Our results suggest that the HA-WBRT strategy could be evaluated for select PCNSL patients with unifocal lesions or those located outside the HAR.
全脑放疗（WBRT）所致海马损伤会导致脑恶性肿瘤患者出现神经认知功能下降。海马回避放疗（HA-WBRT）可能通过减少海马区的辐射暴露来减轻这种情况，但其在原发性中枢神经系统淋巴瘤（PCNSL）中的可行性，在海马受累情况和失败率方面仍未得到评估。本研究评估PCNSL患者诊断时及治疗后的海马受累情况。
我们对2000年至2021年间诊断的278例免疫功能正常的PCNSL患者进行了回顾性分析。在基于大剂量甲氨蝶呤的诱导化疗后，患者接受巩固治疗，包括放疗、单纯阿糖胞苷或自体干细胞移植，或进行观察。在T1加权磁共振成像（MRI）图像上勾勒出海马，并向外扩展5毫米边界以创建海马回避区域（HAR）。海马失败定义为HAR处复发或进展。中位随访时间为38.7个月（范围3.1 - 239.4个月）。
在278例诊断为PCNSL的患者中，39.9%在HAR处出现初始病变。诱导治疗后，212例可评估患者接受了巩固治疗或观察。颅内失败发生在47.6%（n = 101）的患者中，其中66.3%（n = 67）发生在HAR之外，33.7%（n = 34）发生在HAR之内。单灶性疾病（风险比[HR] 0.61，95%置信区间[CI] 0.39 - 0.96，p = 0.025）与海马失败风险较低相关，而初始HAR受累显著增加风险（HR 2.26，95% CI 1.18 - 4.47，p = 0.018）。HAR之外单灶性疾病的患者3年海马失败率最低（6.2%）。对于初始无HAR病变的患者，包含海马区的放疗对海马失败率无显著影响（p = 0.282），其他治疗的3年海马失败率分别为9.2%和14.6%。然而，在初始有HAR受累的患者中，与其他方法相比，包含海马区的放疗显著降低了海马失败率（p = 0.002）。在初始无HAR病变的患者中，传统WBRT的海马失败率为14.6%，HA-WBRT为19%，两者相当（p = 0.734）。
由于总体上海马失败风险较高，不支持常规应用HA-WBRT策略，需要进一步研究以确定其在明确亚组中的可行性和安全性。我们的结果表明，对于某些有单灶性病变或位于HAR之外的PCNSL患者，可以评估HA-WBRT策略。
