原发中枢神经系统淋巴瘤放疗作用观察

目的 探索放疗在原发中枢神经系统淋巴瘤治疗中的作用。方法 回顾分析2010年9月至2017年12月确诊的免疫功能正常的原发中枢神经系统淋巴瘤60例资料,其中50例经由手术或立体定向活检后病理诊断,10例影像学临床诊断。52例患者接受了化疗,其中45例为大剂量甲氨喋呤为主方案,25例为含利妥昔单抗方案。27例患者行计划性放疗,33例未行计划性放疗,其中治疗失败后9例接受了挽救性放疗。结果 中位随访时间28个月(5~70个月)。全组中位生存、中位无进展生存期分别为22个月(5~65个月)、13个月(5~55个月),4年总生存率、无进展生存率分别为61%、33%。计划性放疗组、非计划性放疗组4年总生存率分别为68%、54%(P=0.083),无进展生存率分别为47%、20%(P=0.014)。挽救性放疗组与计划性放疗组4年总生存率差异无统计学意义(P=0.398),全脑放疗≤36Gy、>36Gy组4年总生存率差异也无统计学意义(P=0.136)。结论 放疗是原发中枢神经系统淋巴瘤的综合治疗的一部分,计划性放疗可能使患者在综合治疗中获益,较高的照射剂量不能使患者获益。     

原发性中枢神经系统淋巴瘤的放射治疗进展

原发性中枢神经系统淋巴瘤(PCNSL)是指发生在脑、脊髓、脑膜或眼的罕见侵袭型非霍奇金淋巴瘤,以弥漫大B细胞淋巴瘤占绝大多数,其中又以Non-GCB亚型多见。未经治疗的患者中位生存期仅为3个月,单纯的手术切除肿瘤并没有明显的生存获益。早期单独使用全脑放疗(WBRT),缓解率高,但持续时间短,且延迟性神经系统不良反应是一...     

Potential of chemo-immunotherapy and radioimmunotherapy in relapsed primary central nervous system (CNS) lymphoma

Five patients with relapsed PCNSL were given chemo-immunotherapy (rituximab followed by carboplatin and methotrexate) with osmotic blood-brain barrier (BBB) opening. Four patients achieved CR and one patient had stable disease. Two patients (2/5) had durable responses (survival: 230+, 122+, 82, 42, 38 weeks). One patient later received Indium-111-ibritumomab tiuxetan and Yttrium-90-ibritumomab tiuxetan intravenous, without BBB opening. There was good uptake of Indium-111 ibritumomab tiuxetan in tumor on SPECT scan after 48 h. Estimated radiation doses to brain around and distant from tumor were within safe limits. After Ytrium-90 ibritumomab tiuxetan there was CR in enhancing tumor where the BBB was leaky, but lesions occurred in other brain regions, where the BBB was intact during Yttrium-90 ibritumomab tiuxetan infusion. Imaging and dosimetry with Indium-111 ibritumomab tiuxetan and efficacy with Yttrium-90 ibritumomab tiuxetan suggest the need for future enhanced CNS delivery when using monoclonal or radiolabeled antibodies, as intravenous delivery alone may provide modest clinical benefit due to limited BBB permeability.     

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.     

A new prognostic model using absolute lymphocyte count in patients with primary central nervous system lymphoma

PurposePrimary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma (NHL). Absolute lymphocyte count (ALC) has been suggested to have a prognostic value in several subtypes of NHL. We evaluated the prognostic significance of clinical factors, including ALC, in patients with PCNSL to develop a new prognostic model.MethodsWe analysed prognostic factors, including ALC, at diagnosis in 81 PCNSL patients receiving high-dose methotrexate-based therapy.ResultsThe median ALC at diagnosis was 1210 × 10⁶/L (range, 210–3610), with lymphopenia (≤875 × 10⁶/L) being detected in 27 (33.3%) patients. In the multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) >1 (hazard ratio [HR] 3.18, P = 0.003), age >50 years (HR 4.23, P = 0.012), and lymphopenia at diagnosis (HR 2.83, P = 0.008) remained independent prognostic factors for low overall survival (OS). Lymphopenia was also a significant prognostic factor for progression-free survival (HR 3.17, P = 0.001). By means of a new three-factor prognostic model using ECOG PS >1, age >50 years, and presence of lymphopenia, with 1 point assigned to each factor, we successfully classified the patients into three risk groups: low (0 and 1), intermediate (2), and high (3). The 5-year OS rates of the patients in the low-, intermediate-, and high-risk groups were 74.3%, 21.7%, and 12.5%, respectively (P < 0.001).ConclusionsLow ALC is a useful indicator of poor prognosis in patients with PCNSL. The proposed three-factor model should be validated in large-scale studies.     

Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly

Background Treatment for primary CNS lymphoma (PCNSL) in the elderly is associated with lower response rates and higher risks of acute and late delayed toxicity as compared to younger patients. Temozolomide has emerged as a new alternative treatment for PCNSL and constitutes an attractive option for the elderly because of its favorable toxicity profile. In this study we report outcomes of a consecutive series of PCNSL elderly patients initially treated with an innovative regimen combining methotrexate and temozolomide without radiotherapy or intra-thecal chemotherapy. Methods Histologically confirmed newly-diagnosed PCNSL patients older than 60 years were included. An induction chemotherapy was initially given (methotrexate 3 g /m² on days 1, 10, and 20, and temozolomide 100 mg/m² on days 1–5). Patients achieving a partial or complete response proceeded to a maintenance phase (up to 5 monthly cycles of methotrexate 3 g/m² on day 1, and temozolomide 100 mg/m² days 1–5). Non-responders were treated on an individual basis. Results Among the 23 included patients, a complete response was observed in 55%, and disease progressed in the other 45%. Median event-free survival was 8 months, and median overall survival was 35 months. Grades 3 or 4 toxicities included nephrotoxicity in three patients, and hematotoxicity in five; no neurotoxicity has been observed to date. One patient died while on treatment from complications of intestinal obstruction. Conclusion Our efficacy results are comparable to other reported regimens, with the advantages of a favorable toxicity profile, and absence of intra-thecal chemotherapy. Prospective, controlled studies are warranted to confirm such results.     

Prognostic implication of p27 expression in primary central nervous system lymphoma

To clarify the role of p27/Kip1 (p27) in primary central nervous system lymphomas (PCNSLs), we examined p27 expression by immunohistochemical methods in a series of 22 patients with PCNSL. We attempted to correlate the expression of p27 with proliferation potential and prognosis. Although the MIB-1 labeling index (LI) was lower in tumors with low p27 expression (26.7% ± 17.2% vs 38.1% ± 16.3%), it was not significantly different from that of tumors with high p27 expression (P = 0.1253). Survival analysis revealed that high p27 expression was significantly associated with poorer overall prognosis (P = 0.0011); however, the MIB-1 LI were not associated with prognosis. Our results suggest p27 as a predictor of prognosis in patients with PCNSL.     

原发中枢神经系统恶性淋巴瘤的诊断及治疗

目的：探讨原发中枢神经系统恶性淋巴瘤（PCNSL）的临床、影像学表现,治疗方案选择和预后。方法：对24例PCNSL的诊断、治疗过程、预后进行回顾性分析。结果：PCNSL的临床表现以颅内压增高、局灶占位性病变损伤症状为主,肿瘤可单发或多发;肿瘤影像学缺乏特异性,确诊依靠病理学诊断。结论：PCNSL恶性度高,预后不良,手术全切率低;对确诊病例采用个体化的手术方案结合术后放、化疗是治疗本病的关键,可显著延长患者生存时间。     

原发性睾丸淋巴瘤及原发性中枢神经系统淋巴瘤研究进展：第19届欧洲血液学会年会报道

原发性睾丸淋巴瘤（PTL）是一类少见的结外淋巴瘤,进展迅速,预后不良.对于早期局限性病变,可联合应用以蒽环类为基础的化疗、利妥昔单抗、鞘内注射甲氨蝶呤后行对侧睾丸放疗等.中枢神经系统复发风险极高,鞘内注射甲氨蝶呤可能是最好的防治方法.原发性中枢神经系统淋巴瘤（PCNSL）是一种侵袭性淋巴瘤,预后较差,对现有非霍奇金淋巴瘤标准治疗方案均不敏感,甲氨蝶呤联合阿糖胞苷是目前的标准诱导方案.抗CD20单克隆抗体虽然脑脊液含量低,但仍有治疗效果.高剂量化疗联合自体造血干细胞移植缓解率高,3年总生存率可达87％.     

42例原发性中枢神经系统淋巴瘤患者预后影响因素分析

背景与目的：原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）是发生在脑、脊髓、脑膜或眼的罕见侵袭型非霍奇金淋巴瘤,无CNS之外的部位累及。PCNSL与其他类型淋巴瘤相比,患者生存期短,预后差,且复发率高,未经治疗的患者的中位生存期仅为3个月。近年来研究发现C-MYC、BCL-2、BCL-6、Ki-67等指标在一定程度上影响PCNSL患者预后。因此,通过分析PCNSL相关蛋白表达、治疗方式及其他临床因素对患者预后的影响, 希望为该病的临床治疗及预后评价进一步积累资料。方法：回顾性分析自2013年6月—2021年5月于大连医科大学附属第二医院治疗的42例经病理学检查明确诊断为原发性中枢神经系统弥漫大B细胞淋巴瘤患者的临床资料,包括性别、年龄、病灶数量、美国东部肿瘤协作组（Eastern Cooperative Oncology Group,ECOG）评分、血清乳酸脱氢酶（lactate dehydrogenase,LDH）、病灶是否累及深部脑组织、治疗方案、病理学Hans分型及C-MYC、BCL-2、BCL-6、Ki-67等生物标志物,结合随访调查,了解患者生存时间及生存状况,应用Kaplan-Meier法及log-rank检验分析影响患者无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）的预后相关因素,多因素分析采用COX回归模型。结果：42例PCNSL患者中位发病年龄61岁,男女比例为1.33∶1.00,颅脑增强MRI病灶多呈均匀明显强化。所有患者均接受含有大剂量甲氨蝶呤（high-dose methotrexate,HD-MTX）方案化疗,治疗后评价完全缓解（complete response,CR）20例、部分缓解（partial response,PR）5例,疾病稳定（stable disease,SD）11例,疾病进展（progressive disease,PD）6例。中位PFS为21个月,中位OS为34个月,1年PFS率为63.7%,2年PFS率为47.0%;1年OS率为70.8%,2年OS率为55.6%。单因素分析结果显示,影响PFS的因素是HD-MTX多药联合化疗、鞘内化疗及联合利妥昔单抗。影响OS的因素是ECOG评分≥2、C-MYC（+）、BCL-2及C-MYC双表达、HD-MTX多药联合化疗、鞘内化疗及联合利妥昔单抗。多因素分析结果显示：利妥昔单抗治疗是影响PFS的独立预后因素（P=0.020）,ECOG评分、利妥昔单抗是影响OS的独立预后因素（P=0.007;P=0.046）。与未接受巩固治疗的患者相比,接受巩固治疗患者的中位PFS及OS较高;进一步的亚组分析显示,自体干细胞移植（autologous stem cell transplantation,ASCT）组的中位PFS及OS较全脑放疗（whole brain radiation therapy,WBRT）组高,但差异无统计学意义。结论：PCNSL多发于中老年人,男性多于女性,影像学缺乏特异性。ECOG评分≥2与PCNSL患者较差的OS相关。C-MYC（+）、BCL-2及C-MYC双表达可作为指导危险分层的预后标志物。以HD-MTX为基础的多药联合化疗已经成为PCNSL的首选治疗手段,利妥昔单抗的应用可延长生存期。在全身化疗的基础上,联合局部鞘内化疗可以改善预后。进一步的巩固治疗主要包括ASCT及WBRT,可延长PFS及OS,ASCT可以取得与WBRT相似的疗效,且可避免WBRT的晚期神经毒性,但本研究中因样本量及随访时间的限制,未得出明确的统计学结果。     

原发中枢神经系统恶性淋巴瘤的诊断及治疗

目的:探讨原发中枢神经系统恶性淋巴瘤(PCNSL)的临床、影像学表现,治疗方案选择和预后. 方法: 对24例PCNSL的诊断、治疗过程、预后进行回顾性分析. 结果: PCNSL的临床表现以颅内压增高、局灶占位性病变损伤症状为主,肿瘤可单发或多发;肿瘤影像学缺乏特异性,确诊依靠病理学诊断. 结论: PCNSL恶性度高,预后不良,手术全切率低;对确诊病例采用个体化的手术方案结合术后放、化疗是治疗本病的关键,可显著延长患者生存时间.     

Second malignancies in patients with primary central nervous system lymphoma

Background

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma with distinctive biological behaviors. The evolving treatment of PCNSL has greatly improved the outcome for patients with this disease and has stimulated interest in second malignancies (SMs) in patients diagnosed with PCNSL.

Methods

The records of 129 cases of PCNSL at Mayo Clinic, diagnosed between January 1, 1988, and November 26, 2012, were reviewed. Data on clinical characteristics, laboratory parameters, treatments, outcomes, and SMs were collected. The mean follow-up time was 44.8 months (range, 0.5–240 months; median, 28.0 months).

Results

Altogether, 28 cases with 30 (23.26%) SMs were identified. Twenty (15.50%) patients had prior or synchronous SM. Ten (7.76%) patients developed a subsequent primary cancer after PCNSL. The most common sites of prior or synchronous SMs were prostate (4/20), skin (4/20), and gastrointestinal (3/20). The most common site of the subsequent SM was skin (4/10). Two cases were identified with both prior SM and subsequent SM.

Conclusions

Second malignancies in cases with PCNSL were not uncommon and occurred in nearly a quarter of our cohort. Nonmelanoma skin cancers were frequently seen. Therefore, screening for SMs should also be considered in long-term follow-up of patients with PCNSL. In addition, the high incidence of subsequent cancer, synchronous cancer, and frequently seen nonmelanoma skin cancers may all indicate an immunosuppressed state in patients with PCNSL.     

原发中枢神经系统淋巴瘤诊疗进展

原发中枢神经系统淋巴瘤是一种少见的中枢神经系统恶性肿瘤,以大剂量甲氨蝶呤为基础方案诱导化疗是目前一线治疗,随后全脑放疗作为巩固治疗.迟发神经认知功能障碍出现,尤其是老年人,使缓解患者是否需要全脑放疗或减量放疗需要进一步明确.利妥昔单抗治疗PCNSL,初步研究表明美罗华可能给患者带来获益,但研究证据水平较低.HDC/ASCT对于治疗复发性或难治性PCNSL虽有疗效但毒副作用较大,临床价值尚存争议.     

71例原发颅内中枢神经系统DLBCL预后分析

目的 探讨原发颅内中枢神经系统弥漫性大B细胞淋巴瘤(DLBCL)的预后因素。 方法 回顾分析1991—2015年间收治的经病理和临床证实的 71例原发颅内中枢神经系统DLBCL临床资料。全组患者均进行了化疗,59例进行了放疗,化疗方案以HD-MTX (HD-MTX,66/71)为主,放疗方案以全脑放疗 ±局部推量为主。Kaplan-Meier法计算生存率,Logrank法检验和单因素预后分析,Cox模型多因素预后分析。 结果 放化疗结束时 58例CR, 10例PR,3例PD。5年生存率为43%;5年无疾病进展率为34%。单因素分析显示年龄、KPS评分、单发与多发、是否放疗、放化疗完成时评价、有无复发是影响OS的因素(P=0.000~0.047),多因素分析显示年龄、KPS评分、有无复发是影响OS的因素(P=0.000~0.022)。单因素分析化疗方案、是否放疗、总放疗剂量、全脑剂量、放化疗完成时评价、有无复发是影响PFS的因素(P=0.000~0.028);多因素分析KPS评分、有无复发是影响PFS的因素(P=0.000~0.011)。 结论 年轻、KPS评分高、无复发患者总生存更好,单发、接受放疗、放化疗后疗效好的患者可能更好;KPS评分高、放化疗后疗效好、无复发患者PFS更好,接受含HD-MTX化疗、接受放疗、总的放疗剂量和全脑剂量越高患者PFS可能更好。化疗达CR后是否还放疗及放疗靶区、剂量需进一步研究。     

Relapse of primary central nervous system lymphoma: clinical features, outcome and prognostic factors

Data on relapsed primary central nervous system lymphoma (PCNSL) are limited. We have evaluated the clinical characteristics and outcome of relapsed PCNSL patients from two German trials. Patients with relapsed disease after primary treatment were studied. Primary therapy consisted of high-dose methotrexate-based chemotherapy in all patients. Treatment for relapse was not predetermined. After a median follow-up of 22.5 months, 52 (36%) patients with relapse were identified among 143 patients with complete remission (CR) after primary treatment. The median disease-free survival was 10.25 (3–47.5) months. The median age at relapse was 59 years. Forty-four of 51 evaluable patients relapsed within the CNS, 6 systemically and one both cerebrally and systemically. The median survival time after first relapse was 4.5 (0.5–40.5) months. Karnofsky performance status (KPS) at relapse (P = 0.004), site of relapse (isolated systemic versus other, P = 0.049) and treatment for relapse (versus no treatment, P = 0.001) were independent prognostic factors for survival after relapse in multivariate analysis. Survival of patients with relapsed PCNSL is poor despite high response rates to salvage therapy. Good KPS, isolated systemic relapse and treatment for relapse were significantly associated with longer survival.     

CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma

BackgroundThe diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL.MethodsWe retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion.ResultsCSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively.ConclusionAssessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these results.     

Proton magnetic resonance spectroscopy in immunocompetent patients with primary central nervous system lymphoma

Background: Magnetic resonance spectroscopy imaging (MRSI) non-invasively evaluates the metabolic profile of normal and abnormal brain tissue. Primary central nervous system lymphoma (PCNSL) is a highly aggressive tumor responsive to high-dose methotrexate based regimens. Patients often have complete responses but relapses are common. We characterized the MR spectra of PCNSL patients, correlated MRSI with MRI and evaluated whether early recurrence could be detected by MRSI.Methods: Patients with PCNSL had multi-voxel MRSI before, during, and after treatment. The region of interest was defined using axial FLAIR images. Metabolites assessed were N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), lipid, and lactate. Ratios of Cho/Cr, NAA/Cho, and NAA/Cr were calculated and correlated with MRI. Overall survival (OS), progression free survival (PFS), and relative risks of each of the ratios were determined.Results: MRSI was performed on 11 men and seven women; median age of 59. Sixty-seven MRSI studies were performed, 17 baseline and 48 follow-up studies. Median ratios in 16 pretreated patients were Cho/Cr-1.90, NAA/Cho-0.39, and NAA/Cr-1.27. Two patients had lipid at baseline, five had lactate and two had both. MRSI correlated with tumor response or progression on MRI; in three patients MRSI suggested disease progression prior to changes on MRI. Univariate analysis of metabolite ratios, lipid, and lactate revealed that none significantly affected PFS or OS. Kaplan–Meier analysis of the presence or absence of lipid, lactate or both revealed a trend for increased PFS.Conclusion: MRSI and MRI correlate with tumor response or progression and may allow early detection of disease recurrence. The presence or absence of lipid and/or lactate may have prognostic significance. Further research using MRSI needs to be done to validate our findings and determine the role of MRSI in PCNSL.Presented in part at the 1999 Annual Meeting of the American Academy of Neurology; April 12, 1999.     

原发性中枢神经系统淋巴瘤患者预后的影响因素分析

目的 探讨原发性中枢神经系统淋巴瘤(PCNSL)患者预后的影响因素.方法 收集82例PCNSL患者的临床资料,包括性别、年龄、病灶数量、病灶部位、病灶直径、治疗方法、意识状态、体力状况(PS)评分等一般资料,以及脑脊液(CSF)常规检测指标(CSF蛋白质、CSF氯化物)和生化检测指标[血清乳酸脱氢酶(LDH)、β2微球...     

Prolonged remission of primary central nervous system lymphoma after discontinuation of steroid therapy

Summary The case of a 63-year old man is presented in whom remission of a primary central nervous system lymphoma was achieved by corticosteroids only. After discontinuation of steroid therapy the remission persisted for two and a half years. Recurrences appeared at other sites of the brain, and were steroid resistant.     

原发性中枢神经系统淋巴瘤临床及预后分析

目的:总结原发性中枢神经系统淋巴瘤(PCNSL)的临床特点、诊治方案及临床疗效.方法:回顾收活的21例PCNSL患者,均为病理确诊的B细胞来源非霍奇金淋巴瘤,其中5例接受单纯放疗,16例接受放化疗.对病理学检查、影像学表现、治疗及预后进行总结分析.结果:PCNSL以中老年人多见,发病急,病程短,病情进展快.临床表现复杂,颅内高压为主要表现之一.CT、MR增强扫描病灶多呈均匀明显强化,可单发或多发.21例患者中位生存时间22个月,1、3和5年生存率分别为76.2％、28.6％和4.76％.放化疗疗效优于单纯放疗,P=0.029.结论:PCNSL临床表现多样,影像学缺乏特异性,极易误诊,确诊需要依靠病理学检查,其最佳治疗方案是三维立体定向穿刺活检加放疗、化疗的联合治疗.PCNSL侵袭性强,生存期短,其预后主要与发病年龄、多灶性和体力状况有关.