Characteristics and outcomes of elderly patients with primary central nervous system lymphoma

BACKGROUND:

Approximately 50% of all patients with primary central nervous system lymphoma (PCNSL) are aged ≥65 years; however, this group is relatively understudied, and to the authors's knowledge, optimal treatment for older patients is not well defined.

METHODS:

This was a retrospective review of PCNSL patients aged ≥65 years who were treated at Memorial Sloan‐Kettering Cancer Center between 1986 and 2008. A multivariate analysis of demographic and clinical variables on prognosis and receipt of treatment was performed.

RESULTS:

One hundred seventy‐four patients between the ages of 65 and 89 years were identified; there was a slight predominance of women (52.9%). One hundred forty‐eight patients were treated with chemotherapy at the time of diagnosis (98% with methotrexate‐based therapy) and 31 of these patients also received whole‐brain radiotherapy (WBRT). Sixteen patients received WBRT alone. A radiographic response to chemotherapy was noted in 76% of patients. Ninety patients developed disease progression after initial treatment; 74 received salvage therapy and 48% of these patients responded to salvage treatment. The median overall survival was 25 months (range, 18‐33 months), and the 3‐year survival rate was 36%. Approximately 20.1% of patients were alive for ≥11 years. WBRT was delivered more frequently before 1998, and patients with a history of prior malignancy were less likely to receive WBRT. Age and performance status were identified as the most important predictors of survival. Treatment‐related neurotoxicity at 2 years was strongly associated with receipt of WBRT (P = .0002).

CONCLUSIONS:

PCNSL in the elderly remains sensitive to methotrexate‐based chemotherapy and aggressive treatment may be warranted both at the time of diagnosis and disease recurrence. Cancer 2010. © 2010 American Cancer Society.     

Patterns of treatment in older adults with primary central nervous system lymphoma

BACKGROUND: The incidence of primary central nervous system lymphoma (PCNSL) has increased in recent decades and is highest in people aged >or=65 years. Radiotherapy (XRT) and systemic chemotherapy (CTX), alone or in combination, are reported to extend survival, but treatment-related toxicity is a particular concern in the elderly. The objective of the current study was to identify factors associated with the receipt and type of treatment in a population-based cohort of older PCNSL patients. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims, the authors identified PCNSL cases in adults aged >or=65 years who were diagnosed between 1994 and 2002. Initial treatment was defined as XRT alone, CTX alone, combined CTX and XRT, or no treatment, based on Medicare claims in the 6 months after diagnosis. The authors assessed the effects of age, comorbidity, and sociodemographic characteristics on the odds of receiving treatment. RESULTS: Of 579 PCNSL patients, 464 (80%) received any treatment. XRT alone was the most common modality (46%), followed by combined therapy (33%) and CTX alone (22%). The type of treatment varied by age (P < .0001). The use of CTX alone or in combination with XRT decreased with increasing age, whereas the use of XRT alone increased with age. In adjusted analysis, younger age (P < .01) was found to be predictive of the receipt of any treatment. The use of CTX decreased with age (P < .0001). The median survival was 7 months (95% confidence interval, 6-8 months); no significant time trends were observed. CONCLUSIONS: Although the majority of older PCNSL patients received treatment, most did not receive optimal therapy. Age was found to have the greatest influence on treatment selection. Overall survival in elderly PCNSL patients appears to be poor.     

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。     

利妥昔单抗联合大剂量甲氨蝶呤在原发性中枢神经系统淋巴瘤患者中的应用效果

目的 探讨利妥昔单抗联合大剂量甲氨蝶呤在原发性中枢神经系统淋巴瘤患者中的应用效果.方法 按照入院顺序将84例原发性中枢神经系统淋巴瘤患者分为对照组和观察组,每组42例,对照组接受大量甲氨蝶呤治疗,观察组患者接受利妥昔单抗联合大剂量甲氨蝶呤治疗.比较两组患者的临床疗效、不良反应、生存期和生活质量.结果 观察组患者的治疗总...     

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...     

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.     

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma:a prospective phase Ⅱ trial

Objective: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone(R-FPD) regimen followed by whole-brain radiotherapy(WBRT) for patients with primary central nervous system lymphoma(PCNSL).Methods: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen cons...     

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.     

Association of transcobalamin c. 776C>G with overall survival in patients with primary central nervous system lymphoma

Background:

Chemotherapy for primary central nervous system lymphoma (PCNSL) is based on methotrexate (MTX), which interferes with both nucleic acid synthesis and methionine metabolism. We have reported previously that genetic variants with influence on methionine metabolism are associated with MTX side effects, that is, the occurrence of white matter lesions as a sign of MTX neurotoxicity. Here, we investigated whether such variants are associated with MTX efficacy in terms of overall survival in MTX-treated PCNSL patients.

Methods:

We analysed seven genetic variants influencing methionine metabolism in 68 PCNSL patients treated with systemic and facultative intraventricular MTX-based polychemotherapy (Bonn protocol).

Results:

Median age at diagnosis was 59 years (range: 28–77), 32 patients were female. Younger age (Wald=8.9; P=0.003) and the wild-type C (CC) allele of the genotype transcobalamin c (Tc2). 776C>G (Wald=6.7; P=0.010) were associated with longer overall survival in a multivariate COX regression analysis.

Conclusion:

This observation suggests that the missense variant Tc2. 776C>G influences both neurotoxicity and efficacy of MTX in the Bonn PCNSL protocol.     

Clinical Studies on Primary Central Nervous System Lymphoma： A Report of 31 Cases

OBJECTIVE To analyze the clinical manifestations, neuroimaging and pathological characteristics of primary central nervous system lymphoma （PCNSL） with a normal immunity, and to explore the methods of treatment and diagnosis. METHODS The clinical, laboratory, imaging data and pathological findings and therapeutic efficacy of 31 cases with pathologically proved PCNSL, during a period from July 1995 to June 2006, were analyzed retrospectively. The method of surgery, used in combination with chemotherapy and radiotherapy, was evaluated in 18 cases versus a simple surgical procedure used in 5. Among the total cases, a CHOP regimen was employed in 11 and Teniposide （VM26） plus Semustine （me-CCUN） was used in 7 cases. RESULTS PCNSL had a variety of clinical features, so that its misdiagnosis rate was high. The main clinical findings of PCNSL included intracranial hypertension and （focal） neurologic impairment. No positive result was found in the CSF cellular examination. All of the 31 cases were B-cell lymphoma. Twenty-four of the 31 cases were followed-up, with a follow-up period from 6 to 98 months. The median period of survival of the group who underwent surgery in combination with chemotherapy and radiotherapy was 20 months, while the group with simple surgical therapy was 10 months. CONCLUSION Specific clinical manifestations were usually absent in the patients with PCNSL, giving an uncertain preoperative diagnosis and a poor prognosis. Pathological examination is the only reliable method for a final diagnosis of the disease. The main objective of surgical therapy is to relieve the intracranial hypertension caused by the tumor. Recurrence may occur in a short period following the simple operation. Therefore combined therapy, i.e. surgery plus additional radiotherapy and chemotherapy, should be adopted. This is the key point for extending survival time and improving the quality of life.     

原发性中枢神经系统淋巴瘤35例临床及预后分析

目的：探讨原发中枢神经系统淋巴瘤（PCNSL）临床特点、诊治方案及临床疗效。方法：总结2001年1月-2008年1月收治的35例PCNSL患者,均经病理证实为B细胞来源非霍奇金淋巴瘤并接受放疗,其中25例放疗后接受化疗。结合文献对原发性中枢神经系统淋巴瘤患者的临床特点、病理学检查、影像学表现、治疗及预后进行回顾性分析。结果：本病以中老年人多见,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、MRI增强扫描病灶多呈均匀明显强化,可单发或多发。35例患者中位生存时间23月,1年生存率74．3％,3年生存率25．7％,5年生存率5．71％。肿瘤全切及局部切除者,生存率未见明显统计学差异（P=0．053）,加化疗疗效优于不加化疗（P=0．012）。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,最佳治疗方案是手术加放疗、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、一般状态有关。     

Hyperbaric oxygen therapy for radiation‐induced brain necrosis in a patient with primary central nervous system lymphoma

A 45‐year‐old man who developed brain radionecrosis in the right frontal and left temporoparietal lobes after receiving whole brain radiotherapy and stereotactic radiosurgery for primary central nervous system lymphoma. Since high dose steroid treatment failed and he declined to undergo surgery, he was referred to hyperbaric oxygen (HBO) therapy. Both clinical and radiological findings improved after HBO therapy. Steroid requirements were also reduced. HBO therapy may have a potential value in treatment of brain radionecrosis. J. Surg. Oncol. 2009;100:732–735. © 2009 Wiley‐Liss, Inc.     

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.     

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35例临床及预后分析

目的:探讨原发中枢神经系统淋巴瘤(PCNSL)临床特点、诊治方案及临床疗效。方法:总结2001年1月-2008年1月收治的35例PCNSL患者,均经病理证实为B细胞来源非霍奇金淋巴瘤并接受放疗,其中25例放疗后接受化疗。结合文献对原发性中枢神经系统淋巴瘤患者的临床特点、病理学检查、影像学表现、治疗及预后进行回顾性分析。结果:本病以中老年人多见,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、MRI增强扫描病灶多呈均匀明显强化,可单发或多发。35例患者中位生存时间23月,1年生存率74.3%,3年生存率25.7%,5年生存率5.71%。肿瘤全切及局部切除者,生存率未见明显统计学差异(P=0.053),加化疗疗效优于不加化疗(P=0.012)。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,最佳治疗方案是手术加放疗、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、一般状态有关。     

R-FPD方案治疗初治原发中枢神经系统淋巴瘤的前瞻性研究

目的:评估利妥昔单抗联合福莫司汀、培美曲塞、地塞米松方案(R-FPD)治疗原发中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)的安全性、有效性和可行性,初步探索生物标志物在PCNSL治疗中的意义。方法:本研究为前瞻性、单中心、单臂Ⅱ期临床试验。分析2018年7月至2019年7月郑州大学第一附属医院确诊的初治PCNSL患者。全组患者均接受R-FPD方案一线化疗。主要研究终点为客观缓解率(objective response rate,ORR),疾病控制率(disease control rate,DCR),无进展生存期(progression free survival,PFS),总生存期(overall survival,OS)。次要研究终点为不良反应(adverse reaction,ADR)。结果:共12例患者纳入此研究,4个周期治疗后疗效评估为完全缓解(complete response,CR)6例,部分缓解(partial response,PR)2例,疾病稳定(stable disease,SD)1例,疾病进展(...