原发性中枢神经系统淋巴瘤诊治进展

原发性中枢神经系统淋巴瘤(primarycentralnervoussystemlymphoma,PCNSL)是原发于脑、眼和脊髓的非霍奇金氏淋巴瘤,临床上较罕见,近数十年来发病率逐渐上升。PCNSL多见于老年患者,病理类型、预后因素和治疗方案有别于全身性非霍奇金淋巴瘤(NHL)。PCNSL病理类型以弥漫大B细胞为主,年龄和(performancestatus)PS是最重要的预后因素,预后较全身性NHL差。目前PCNSL尚无标准治疗方法,一般采用化疗和放疗联合的治疗措施。手术仅起到诊断作用。PCNSL对放疗高度敏感,但单纯放疗有效维持时间短。化疗在治疗PCNSL中不可缺少,但CHOP方案对PCNSL无效。大剂量甲氨蝶呤(HD-MTX)是最有效的药物,大剂量阿糖胞苷(HD-AraC)是常用的药物之一。因此,现阶段PCNSL采用含HD-MTX或/和HD-AraC等的联合化疗,同时鞘内注射MTX、AraC和地塞米松(DXM)。放疗疗效差,放疗应在化疗结束后进行。联合化、放疗对60岁以上患者可造成严重的远期神经毒性,对老年患者可选择单纯化疗和延迟放疗的治疗方法。自体造血干细胞支持下超大剂量化疗疗效优于历史对照。新药Temozolomide、Temozolomide联合美罗华、Topotecan、放射免疫治疗药物Y90标记CD20单抗等对PCNSL取得一定效果,值得进一步研究。     

原发性中枢神经系统淋巴瘤治疗进展

原发性中枢神经系统淋巴瘤（PCNSL）恶性度高,预后较差。PCNSL目前无标准治疗方案,单纯手术或单纯放疗效果较差,以氨甲喋呤（HD-MTX）为基础的综合治疗可改善患者生存率。综合化疗后的放疗以全脑放疗为首选,但放疗可导致老年患者神经毒性。化疗后自体干细胞移植及靶向药物可改善患者预后,并可降低神经毒性发生率。     

原发性中枢神经系统淋巴瘤的治疗进展

原发性中枢神经系统淋巴瘤（PCNSL）是一种少见疾病,至今尚无标准治疗方案。单纯放疗复发率高,生存期短。放疗宜在化疗结束后进行。化疗联合标准放疗明显降低了复发率,并延长了生存期,但神经毒性发生率高。老年患者易出现神经毒性,不建议放疗,应首选单纯化疗;年轻患者可将放疗作为难治复发时的二线治疗。目前,以大剂量甲氨蝶呤为主的化疗已成为PCNSL的一线治疗,大剂量阿糖胞苷为最常联合的药物。年轻患者可选用包含一些新药如甲基苄肼、替莫唑胺的化疗方案。替莫唑胺为老年患者一种有前途的新药。预防性鞘内化疗的必要性尚未达成共识。自体造血干细胞支持下的大剂量化疗对年轻的初发及复发PCNSL患者均有效。手术通常用于PCNSL诊断。糖皮质激素不宜在取得病理组织前使用。      

原发中枢神经系统淋巴瘤的治疗进展

原发中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）是仅累及脑实质、脊髓、眼、颅神经及脑膜 ,无中枢神经（central nervous system,CNS）以外部位受累的一类结外非霍奇金淋巴瘤。目前,治疗主要是以大剂量甲氨蝶呤为基础的化疗,联合大剂量化疗/自体干细胞移植（autologous stem cell transplantation,auto-HSCT）或减量的全脑放疗。但缓解率较低,不良反应较大。研究显示,10%～15%的患者对诱导化疗原发耐药,即使治疗有效,仍有50%的患者复发。近年来,PCNSL遗传学和分子的研究极大地促进了生物学机制的理解。小分子药物和靶向药物治疗的前景可观,有望减少不良反应的同时,提高患者缓解率、延长寿命。本文主要对目前PCNSL的新治疗方向进行综述。      

原发性中枢神经系统淋巴瘤的治疗进展

原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma ,PCNSL ）是一种罕见的结外淋巴瘤,其病理类型多为弥漫性大B 细胞淋巴瘤,影像学多表现为单发的脑实质深部病变,MRI 可有多种强化形态。目前,以大剂量甲氨蝶呤为主的化疗已成为PCNSL 的一线治疗。放、化疗的结合可延长患者的生存期,但神经毒性发生率较高。大剂量化疗联合自体干细胞移植对复发/ 难治性PCNSL 有效。替莫唑胺和利妥昔单抗不良反应小、耐受性好,可作为PCNSL 治疗的选择。PCNSL 的预后受血清LDH浓度、年龄、ECOG 评分/KPS 评分、脑脊液蛋白浓度、肿瘤定位等多种因素的影响。      

原发性中枢神经系统淋巴瘤的预后因素和治疗进展

原发性中枢神经系统淋巴瘤(PCNSL)是原发于脑和脊髓的非霍奇金氏淋巴瘤(NHL)，临床上较罕见，仅占脑肿瘤的1％和结外NHL的1％-2％。近数十年来发病率逐渐上升。由于部位特殊，现有NHL的预后因素和治疗原则不适用于PCNSL。PCNSL发病率低，目前尚无标准的预后因素和一线标准治疗方案，但随着临床治疗经验的不断积累，在治疗上已取得一定的共识，使PCNSL中位生存期由早年单纯放疗的13-16个月增加到目前综合治疗的30-36个月，疗效有较明显提高。本文着重于评述近年来在免疫功能正常的PCNSL预后因素的确立和临床治疗方面取得的进展。目前PCNSL一般采用化疗和放疗联合的治疗措施，手术仅起到诊断作用。化疗在治疗PCNSL中不可缺少，但CHOP方案对PCNSL几乎无效。大剂量甲氨蝶呤(HD—MTX)是最有效的药物，大剂量阿糖胞苷(HD—Ara—C)是另一个常用的有效药物，鞘内给药有助于预防脑脊髓膜的肿瘤种植。PCNSL对放疗高度敏感，但单纯放疗复发率高，远期疗效差，放疗应在化疗完成后进行，多常用全颅加侵犯野放疗。为降低化放疗的远期神经毒性，有人尝试采用单纯化疔治疗PCNSL，对于获得完全缓解的患者放疗延迟至复发后再进行，远期疗效有待确定。自体造血干细胞移植支持下超大剂量化疗和抗CD20单克隆抗体也试用于治疗PCNSL，取得一定效果。目前全身HD—MTX、化疗后放疗的次序、年龄和PS是PCNSL最重要的预后因素。因此，采用含HD—MTX或／和HD—Ara—C等的联合化疔，同时鞘内注射MTX、Ara—C和地塞米松(DXM)，结合颅脑放疗是现阶段治疗PCNSL最常用的治疗模式。     

34例原发性中枢神经系统恶性淋巴瘤临床分析

目的：分析免疫功能正常的中国人原发性中枢神经系统淋巴瘤（PCNSL）的临床资料,探讨PCNSL的临床特征,评价大剂量甲氨蝶呤（HD-MTX）加全脑放疗（WBRT）治疗PCNSL的疗效.方法：回顾性分析34例经病理证实的PCNSL患者的临床资料以及治疗效果,Kaplan-Meier法分析患者生存期.结果：34例PCNSL患者中B细胞淋巴瘤31例（91.2%）,T细胞淋巴瘤3例（8.8%）;所有患者治疗后评价完全缓解率（CR）41.2%,2年生存率60.2%;病理类型和是否接受HD-MTX加放疗是影响PCNSL生存期的主要原因（P＜0.05）.结论：PCNSL以颅内高压为主要表现,B细胞亚型占绝对优势,具有独特的预后因素,HD-MTX联合放疗是PCNSL有效的治疗方法.     

原发中枢神经系统淋巴瘤(二)

单纯放疗以前是PCNSL的主要治疗手段，目前的主要治疗原则为化疗和放疗综合治疗。大剂量MTX化疗加全脑照射是目前公认的PCNSL有效治疗方法，能明显改善患者的生存率，但长期神经毒性发生率明显增多。为改善生活质量，减少并发症，20世纪90年代初开始应用单纯化疗作为一线治疗方案，完全缓解后复发的患者再考虑放疗(延迟放疗)。     

原发性中枢神经系统淋巴瘤的治疗

原发性中枢神经系统淋巴瘤(PCNSL)是一种较少见的中枢神经系统恶性肿瘤,总体预后欠佳,主要治疗方法包括手术、放疗和化疗.立体定向活检术以其微创、便捷的优点,已经成为确诊PCNSL的常规方法.全脑放疗是多病灶性PCNSL的标准化治疗方法,可短期内延缓肿瘤进展.以大剂量甲氨蝶呤为基础的治疗方案大大改善了PCNSL的治疗效果,成为PCNSL的有效治疗措施.有效的综合治疗是延长PCNSL患者生存期和改善生命质量的关键.     

原发中枢神经系统淋巴瘤研究进展

原发中枢神经系统淋巴瘤(PCNSL)是原发于颅内的结外非霍奇金淋巴瘤,是一种罕见的高侵袭性淋巴瘤,预后较差.近年来,关于PCNSL的治疗方案尚无定论,以往的治疗包括手术、放疗、化疗等.目前大多认为综合治疗可以提高患者的生存率,而联合化疗药物的选择和预防性鞘内注射化疗药物在其治疗中占有重要地位.     

原发性中枢神经系统淋巴瘤研究进展

原发性中枢神经系统淋巴瘤（Primary Central Nervous System Lymphoma,PCNSL）是一种比较罕见的结外淋巴瘤.好发于免疫缺陷的人群中.但近年来在免疫力正常人群中发病率不断增加,目前其发病机制仍有争论.其病理形态与颅外淋巴瘤相似,病理类型一般为中高度恶性非霍奇金淋巴瘤（NHL）,多为弥漫型大B细胞来源,来源于T细胞的比较少见.影像学表现为单发或多发的深部脑实质或血管周围病变及脑膜等处的病变.CT平扫呈圆形或卵圆形等密度占位病变,边界相对清楚,周围有水肿带,应与胶质瘤、脑膜瘤、转移瘤鉴别.脑脊液淋巴细胞亚群的流式分析能够对诊断脑膜淋巴瘤有所帮助.在临床表现方面与其它颅内肿瘤无明显差异.放化疗综合治疗有可能提高治愈率.化疗采用以MTX为主的化疗,全脑放疗已被公认为治疗PCNSL的有效手段.放、化疗的顺序在一定程度上可能影响患者的生存期,目前推荐采用先放后化的治疗方法.预后取决于多种因素如年龄、确诊时间、病变部位、肿瘤组织类型、治疗措施的选择、患者有否免疫抑制状态等.     

Advances for the treatment of primary central nervous system lymphoma (review)

Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin's lymphoma arising in the CNS. This review will focus on the recent advances in the treatment of PCNSL. Combined methotrexate-based chemotherapy and radiation therapy is the standard treatment for PCNSL. A median overall survival of 40-60 months is obtained, however, neurotoxicity is a major problem. Preservation of cognitive function appears better after chemotherapy alone, therefore, there are increasing reports that radiotherapy is deferred after chemotherapy. At the moment, the findings of multicenter randomized trials should be awaited to clarify whether deferring radiotherapy in patients responding to chemotherapy allows them to maintain a better quality of life without increasing the risk of local recurrence. The well-designed, multicenter and randomized trials will elucidate the issues, such as best chemotherapy regimen, no brain irradiation in responder and second-line treatment.     

Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10.

PURPOSE: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We prospectively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL. PATIENTS AND METHODS: We enrolled 102 newly diagnosed, immunocompetent patients with PCNSL; 98 were assessable. Patients first received five cycles of methotrexate 2.5 g/m(2), vincristine, procarbazine, and intraventricular methotrexate (12 mg). Whole-brain radiotherapy (RT) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT. RESULTS: Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36% had a partial (> 50%) response, for a 94% response rate. Median progression-free survival was 24.0 months and overall survival was 36.9 months. Age was an important prognostic factor; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older (P <.001). Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy, half of which was hematologic. However, 12 patients (15%) experienced severe delayed neurologic toxicity, eight of whom died. CONCLUSION: This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone. A high-dose methotrexate-based regimen produced a high response rate before RT was administered. High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL, but neurotoxicity is a delayed risk of this approach.     

Is There a Role for Radiotherapy in the Primary Management of Primary Central Nervous System Lymphoma? A Single-centre Case Series

AimsIn recent years, the optimum primary management of primary central nervous system lymphoma (PCNSL) has evolved from combined modality chemoradiotherapy to chemotherapy alone. We describe a single-centre case series of PCNSL with a view to assessing the role of radiotherapy in primary disease management.Materials and methodsWest of Scotland PCNSL cases between 2001 and 2010 were identified by neuropathology. Observational data were collected retrospectively from case notes and electronic systems.ResultsForty-nine patients fulfilled the eligibility criteria. The median age was 61 years. Chemotherapy with a view to consolidation radiotherapy on completion was delivered to 61% (n = 30). Regimens varied, but were generally methotrexate-based. Chemotherapy was discontinued prematurely in 80% (n = 24) due to progressive disease (n = 12), intolerable toxicity (n = 7) or death (n = 4). In all patients who progressed or did not tolerate chemotherapy, treatment was changed to immediate salvage radiotherapy; modal irradiation was 40 Gy. Radiotherapy alone was delivered to those not suitable for chemotherapy (18%, n = 9) and best supportive care to those with poor performance status (18%, n = 9). The overall median survival was 8 months. In those receiving single modality radiotherapy or chemotherapy, the median survival was 5 and 8 months, respectively. For those completing chemoradiotherapy in its entirety, 3 year survival was 100%; in groups receiving salvage radiotherapy despite progressive disease or chemotherapy toxicity, moderate survival was maintained with immediate radiotherapy with 3 year survival rates of 33 and 60%, respectively.ConclusionsAlthough chemotherapy alone remains the optimal treatment of PCNSL, out with clinical trials only a minority of patients complete chemotherapy due to toxicity and disease progression; in such patients, immediate salvage radiotherapy provides an effective and safe alternative with maintenance of good outcomes.     

原发性中枢神经系统淋巴瘤的临床特征分析

 目的　分析原发性中枢神经系统淋巴瘤（PCNSL）的临床特征,探讨影响疾病的预后因素,并对不同的治疗方案进行评价。方法　回顾性分析初发PCNSL患者的临床资料、治疗经过及随访结果,应用Log-rank进行单因素分析,应用COX回归模型进行生存资料的多因素分析。结果　共收集PCNSL初发病例64例,中位年龄54.9岁,男性多于女性,肿瘤单发62 %（40／64）,深部病变占54 %（33／61）。在我科诊治的具有完整治疗资料的患者26例,其中19例患者初始治疗为单纯化疗,6例为全颅放疗（WBRT）后1个月进行化疗,1例患者初治时仅行WBRT。中位生存时间为17个月,血红蛋白≥9 g／L患者的生存时间长于血红蛋白＜9 g／L患者。年龄>60岁、性别、体能状态、病变部位等因素对预后无明显影响。应用含大剂量甲氨蝶呤（HD-MTX）或替尼泊苷的方案化疗者的预后优于未使用者,化疗联合放疗可能有助于改善患者的预后（χ2＝3.24,P＝0.07）,应用CHOP方案（环磷酰胺、多柔比星、长春新碱、泼尼松）、利妥昔单抗、鞘内注射化疗药物等与预后关系不大;多因素分析提示HD-MTX是影响PCNSL患者生存时间的独立有利因素,颅内病灶部位、病灶的多少、是否联合放化疗等均不是影响预后的独立因素。结论　PCNSL预后较差,应用HD-MTX、替尼泊苷等药物可改善患者的预后,贫血尤其中重度贫血患者预后不良。     

Primary central nervous system lymphoma: biological aspects and controversies in management

INTRODUCTION: This review was produced from the workshop on primary central nervous system lymphoma (PCNSL) at the European Cancer Conference (ECCO 13) in Paris in 2005. It covers the presentation and biological features of the disease (Professor Khe Hoang-Xuan). The role of chemotherapy, including the management of intraocular lymphoma and the use of high dose chemotherapy followed by autologous stem cell transplantation for PCNSL, is discussed (Dr. Andres Ferreri) as well as controversies in the use of whole brain radiotherapy (WBRT) after chemotherapy (Dr. Michele Reni). The topics covered with discussants at the workshop are also summarised. CONCLUSION: The imaging of the brain and the histopathology including detailed immunohistochemistry is of vital importance in making an accurate diagnosis of the disease and understanding the extent of spread of the disease in the CNS. The importance of high dose methotrexate (HDMTX; dose > or = 1g/m(2)), as the most active drug in the treatment of PCNSL, is stressed. The authors recommend that HDMTX alone or in combination with other active chemotherapy agents should be used to treat PCNSL followed by whole brain radiotherapy (WBRT) unless contraindicated because of the advanced age of the patient and existing cognitive impairment. Only published protocols should be used unless the patient is to be offered a trial that has either national or international support. Baseline neuropsychological tests should be carried out before treatment and repeated during and after treatment. The risks of cognitive impairment associated with the disease, with methotrexate - containing chemotherapy and with whole brain radiotherapy should be explained to patients and relatives when obtaining informed consent. Long-term survival, with current treatment regimes, is possible with PCNSL but this appears limited to patients less than 60 years of age at presentation (mostly patients less than 50 years of age).     

Chemo-radiotherapy for malignant brain tumors

I) Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. II) Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. III) Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. IV) Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors.