Iwadate Yasuo, Suganami Akiko, Ikegami Shiro, Shinozaki Natsuki, Matsutani Tomoo, Tamura Yutaka, Saeki Naokatsu, Yamanaka Ryuya
Department of Neurological Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8670, Japan,
J Neurooncol. 2014 Apr;117(2):261-8. doi: 10.1007/s11060-014-1379-4. Epub 2014 Feb 1.
The survival of patients with primary CNS lymphoma (PCNSL) has been improved by high-dose methotrexate (HD-MTX). Since the combination therapy of HD-MTX and whole-brain radiotherapy (WBRT) carries a significant risk for delayed neurotoxicity, it is important to know the therapeutic potential and prognostic factors for HD-MTX without WBRT. We retrospectively reviewed 46 consecutive patients with PCNSL treated with a HD-MTX (3.5 g/m(2)) and deferred WBRT. Patients who achieved complete response or partial response after three courses of HD-MTX were cautiously followed-up without additional treatment. Patients who had either stable disease, progressive disease, or disease relapse were offered salvage therapy. The median progression-free survival period was 10 months and the median overall survival period was 52 months, with a 5-year survival rate of 39 %. Nineteen patients (49 % of the evaluable patients) achieved a complete response at the initial response assessment. Involvement of deep structures of the brain (corpus callosum, basal ganglia and brainstem) was significantly associated with the worse progression-free survivals (p = 0.0058) and overall survivals (p = 0.0177). Gene expression profiling analysis by microarray was compared in eight patients between PCNSLs located in the deep structures of the brain and non-deep-seated tumors. The result showed that up-regulation of signal transduction-related genes and down-regulation of catalytic activity-related genes in the non-deep-seated PCNSL compared with the deep-seated tumors. The present study shows that PCNSL located in non-deep structures of the brain responds better to HD-MTX alone than those involved deep-structures.
大剂量甲氨蝶呤（HD-MTX）改善了原发性中枢神经系统淋巴瘤（PCNSL）患者的生存率。由于HD-MTX与全脑放疗（WBRT）联合治疗存在显著的迟发性神经毒性风险，了解不进行WBRT时HD-MTX的治疗潜力和预后因素很重要。我们回顾性分析了46例连续接受HD-MTX（3.5 g/m²）治疗且推迟WBRT的PCNSL患者。在接受三个疗程的HD-MTX治疗后达到完全缓解或部分缓解的患者在不进行额外治疗的情况下接受密切随访。疾病稳定、进展或复发的患者接受挽救治疗。无进展生存期的中位数为10个月，总生存期的中位数为52个月，5年生存率为39%。19例患者（占可评估患者的49%）在初始缓解评估时达到完全缓解。脑深部结构（胼胝体、基底神经节和脑干）受累与较差的无进展生存期（p = 0.0058）和总生存期（p = 0.0177）显著相关。对8例脑深部结构PCNSL患者和非深部肿瘤患者的基因表达谱进行了微阵列分析比较。结果显示，与深部肿瘤相比，非深部PCNSL中信号转导相关基因上调，催化活性相关基因下调。本研究表明，位于脑非深部结构的PCNSL对单独使用HD-MTX的反应比深部结构受累的PCNSL更好。
