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来源：桓兴医讯 原发性中枢神经系统淋巴瘤是一种具有独特临床行为的侵袭性肿瘤，对化疗和放疗高度敏感，中枢神经系统以外很少侵及，但局部复发率高。尽管目前治疗有进步、生存数据明显改善，但原发性中枢神经系统淋巴瘤患者的预后仍不佳，嘿嘿，数据为证，5年生存率20-30%，10年10-20%，临床试验所报告的治疗结果与临床实际工作中所观察到的结果之间有巨大的差异（你知道为啥很多肿瘤大咖建议自己的患者尽可能参加临床试验了吧，不仅仅是为了省钱。注意，此试验非彼实验也）。这个领域的临床研究主要集中在甄别新的有效药物和治疗组合，以增加诱导化疗的疗效和耐受性，还集中在巩固治疗策略的改进、优化放疗耐受性、寻找有效的全脑放疗的替代方法 《柳叶刀血液病学分册》2017年10月17日在线先发 http:///journals/lanhae/article/PIIS2352-3026(17)30174-6/fulltext 原发性中枢神经系统淋巴瘤患者大剂量甲氨喋呤为基础的化疗免疫治疗后用全脑放疗或者自体干细胞移植作为巩固治疗策略：“国际结外淋巴瘤研究组32”2期临床试验的第二个随机化结果 背景 “国际结外淋巴瘤研究组32（IELSG32）”试验是一项国际性随机化2期研究，要在新诊断出的原发性中枢神经系统淋巴瘤患者的治疗中，阐明两个重要临床问题，第一个随机化结果表明，与所检测的其它联合诱导方案相比，甲氨蝶呤、阿糖胞苷、噻替哌和利妥昔单抗（称为MATRix治疗方案）是与更好的转归相关的联合诱导方案。在此，我们报告第二个随机化结果，这个结果要阐明大剂量以甲氨喋呤为基础的化疗免疫治疗以后，在自体干细胞移植（ASCT）支撑下的根治性化疗的疗效，以作为全脑放疗的替代方法。 方法 将HIV阴性、ECOG体能状态评分0-3分、新诊断的原发性中枢神经系统淋巴瘤患者（年龄18-70岁）随机分组，一组接受4个疗程的第一天甲氨喋呤3.5mg/m2、第二天第三天每天两次的阿糖胞苷2g/m2（A组），第二组接受相同的联合用药再加-5、0天时两个剂量的利妥昔单抗375mg/m2（B组），第三组接受相同的甲氨喋呤-阿糖胞苷-利妥昔单抗的联合用药再加第四天噻替哌30mg/m2（C组），这三组的治疗每三周一重复。诱导治疗后缓解或肿瘤稳定、充分采集了自体外周血干细胞、且没有医源性副作用的患者符合第二次随机化条件，随机化进行全脑放疗（4-10兆电子伏的光子，每周5次分割，分割大小为180 cGy，自最后一个疗程的诱导后4周内开始全脑放疗；D组）或卡莫司汀-噻替哌有条件的自体干细胞移植（ASCT）（-6天卡莫司汀400mg/m2、-5天和-4天噻替哌每12小时一次5mg/kg，随后再输注自体外周血干细胞；E组）。对两种随机化分组均采用序列区组随机化设计，每一分层采用计算机生成的随机化列表，分组后揭盲。主要终点为2年无进展生存，诱导组和对诱导化疗有缓解作为分层指标。在修订的意向性治疗基础上进行分析。这项研究已在ClinicalTrials.gov网站注册，注册号NCT01011920。 结果 2010年2月19日至2014年8月27日，从5个国家的53家医疗中心招募了227名患者，227名患者入组，其中219名可评价。符合第二次随机化条件的122名患者中，118名随机分组到了全脑放疗组和自体干细胞移植组（每组各59名患者），从而构成本研究的患者群。全脑放疗和自体干细胞移植均有效，均获得了事先确定的疗效阈值，即D、E两组头52名患者中2年时至少有40名无进展生存者。全脑放疗组和自体干细胞移植组之间2年无进展生存率无明显差异：D组80%（95%CI，70-90）、E组69%（59-79）（风险比1.50，95%CI，0.83-2.71，p=0.17）。两种巩固治疗均可耐受。正如所预期的，4级非血液学毒性少见，自体干细胞移植治疗的患者比全脑放疗的患者血液学毒性更多。记录到两名毒副作用死亡，均为接受自体干细胞移植的患者。 解释 年龄≤70岁的原发性中枢神经系统淋巴瘤患者大剂量甲氨喋呤为基础的化疗免疫治疗后，用全脑放疗和自体干细胞移植作为巩固治疗均可行、有效。在进行治疗决策时应考虑全脑放疗后认知障碍的风险和并发症。 Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial Background The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. Methods HIV-negative patients (aged 18–70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0–3 were randomly assigned to receive four courses of methotrexate 3·5 g/m2 on day 1 plus cytarabine 2 g/m2 twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m2 on days −5 and 0 (group B); or the same methotrexate–cytarabine–rituximab combination plus thiotepa 30 mg/m2 on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4–10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine–thiotepa conditioned ASCT (carmustine 400 mg/m2 on day −6, and thiotepa 5 mg/kg every 12 h on days −5 and −4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer-generated randomisation list was used within each stratum. No masking after assignment to intervention was adopted. The primary endpoint was 2-year progression-free survival, with induction group and response to induction chemotherapy as stratification parameters. Analyses were done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01011920. Findings Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited from 53 centres in five countries. 219 of 227 enrolled patients were assessable. Of the 122 patients eligible for the second randomisation, 118 patients were randomly assigned to WBRT or ASCT (59 patients per group) and constitute the study population. WBRT and ASCT were both effective, and achieved the predetermined efficacy threshold of at least 40 progression-free survivors at 2 years among the first 52 patients in both groups D and E. There were no significant differences in 2-year progression-free survival between WBRT and ASCT: 80% (95% CI 70–90) in group D and 69% (59–79) in group E (hazard ratio 1·50, 95% CI 0·83–2·71; p=0·17). Both consolidation therapies were well tolerated. Grade 4 non-haematological toxicity was uncommon; as expected, haematological toxicity was more common in patients treated with ASCT than in those who received WBRT. Two toxic deaths (infections) were recorded, both in patients who received ASCT. Interpretation WBRT and ASCT are both feasible and effective as consolidation therapies after high-dose methotrexate-based chemoimmunotherapy in patients aged 70 years or younger with primary CNS lymphoma. The risks and implications of cognitive impairment after WBRT should be considered at the time of therapeutic decision. 责任编辑：肿瘤资讯-Ruby |
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