Incidence Of Primary Central Nervous System Lymphoma Research Articles

Primary central nervous system lymphoma with initial presentation of cerebral salt-wasting syndrome shifting to syndrome of inappropriate antidiuretic hormone secretion: A case report

Background. Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma which may affect brain parenchyma. Hyponatremia can be present as one of the complications, either due to neuronal injury arising from in-situ tumor and/or surgical resection (resulting in cerebral salt wasting syndrome/CSWS) or indolent, slowly progressing and often asymptomatic one as a consequence of ongoing chronic illness (so-called syndrome of inappropriate antidiuretic hormone/SIADH). Differentiating between the two is critical, since each diagnosis has a starkly different treatment approach which may exacerbate one another. Case presentation. Herein, we reported a case of a 48-year-old immunocompetent male who presented with diplopia, hallucination, imbalance, and dizziness, later to be diagnosed with PCNSL on multiple brain regions. He suffered from symptomatic hyponatremia post-surgically as a result of CSWS which in turn responding well to intensive dose of desmopressin acetate and fluid replenishment. However, as the disease progressed, hyponatremia also relapsed but was refractory to the same treatment approach. After subsequent investigations, patient was known to have SIADH. Treatments tailored to SIADH including fluid restriction and administration of hypertonic saline as well as tolvaptan lead to stabilization of sodium levels and significant clinical improvements. Conclusion. Post-operative hyponatremia in the setting of a PCNSL continues to be a complex issue. It underscores the importance of careful clinical assessment, monitoring, and the need for flexibility in diagnosis and management strategies. Furthermore, it highlights the challenges of distinguishing between CSWS and SIADH, two conditions with similar laboratory findings but divergent management approaches. Recognizing the subtleties in clinical presentation and responding appropriately can greatly influence patient outcomes. The rising incidence of PCNSL in immunocompetent individuals also needs a heightened awareness and understanding of its presentations and potential post-operative complications among clinicians.

Whole-Exome Sequencing Revealed the Mutational Profiles of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) is a highly aggressive type of extranodal non-Hodgkin lymphoma, of which approximately 90% of the cases are diffuse large B-cell lymphoma (DLBCL). In recent years, the incidence of PCNSL has significantly increased in women and older men. Although advanced treatments such as high-dose methotrexate (HD-MTX) and targeted agents have been introduced, the prognosis of these patients remains poorer than those with other forms of non-Hodgkin's lymphoma. Twelve cases of Chinese PCNSL were analyzed to detect their genetic alterations using whole-exome sequencing (WES). We identified 448 potential somatic single nucleotide variants (SNVs) with a median of 12 SNVs per PCNSL sample and 35 small indels with potentially protein-changing features in 9 PCNSL samples. We found that myeloid differentiation factor 88 (MYD88) had the highest mutation frequency, which affected the activity of the nuclear factor-κB (NF-κB) pathway. PCNSL samples with low-density lipoprotein receptor-related protein 1B (LRP1B) mutations had a higher mutation rate than samples with wild-type LRP1B. Polycystic kidney and hepatic disease 1 (PKHD1), the causal gene of autosomal recessive polycystic kidney disease (ARPKD), was identified in 2 PCNSL cases and exhibited missense mutations. Pathway analysis revealed enrichment in pathways associated with central carbon metabolism in cancer, renal cell carcinoma, nicotine addiction, bladder cancer, and long-term depression. WES revealed significantly mutated genes associated with the molecular mechanisms of PCNSL, which could serve as therapeutic targets to improve patient outcomes.

Zanubrutinib, Lenalidomide, Rituximab, Temozolomide and Methotrexate (RLZT±MTX) As First-Line Treatment for Newly Diagnosed PCNSL: A Prospective, Open-Lable, Multicenter Clinical Trial

Backgroud: Primary central nervous system lymphoma (PCNSL) represents approximately 2% of all primary central nervous system tumors and 4% to 6% of all extranodal lymphomas. The incidence of PCNSL has been increasing in recent years, and the median age at diagnosis was 65 years old. Most PCNSLs are diffuse large B-cell lymphoma (DLBCL; 90%-95%). PCNSL-DLBCL is a rare and highly aggressive lymphoma, due to its characteristics and special involved sites，previous treatment effect is disappointing with poor prognosis. Aim: This study aims to evaluate the clinical efficacy and safety of Zanubrutinib combined with Lenalidomide, Temozolomide and Rituximab monoclonal antibody ±Methotrexate (RLZT±MTX) as first-line treatment for primary central nervous system lymphoma, especially in elderly patients who cannot tolerance to intensive chemotherapy. Methods: The prospective, multicenter, open-label study planned to enroll 40 patients(Registration number:ChiCTR2000039485). Group A (RLZT+MTX) :eligible 20 young patients were ≤65 years, with normal kidney function. Patients in arm A were treated with regimen 1 and 2 alternately, each 3 courses, A total of 6 courses; Group B (RLZT) :eligible 20 elderly patients were >65 years or ≤65 years frail patients or patients with kidney dysfunction, regimen 2 was used for a total of 6 courses. Regimen 1: high-dose MTX (3.5g/m2) every 28 days; Regimen 2: RLZT (Rituximab 375mg/m2 IV D1, Lenalidomide 15mg/m2 D1-21, Zanubrutinib 160mg bid D1-21, Temozolomide 150mg/m2 Po D1-5) every 28 days. Note: 1. In group A, if patients who did not have a CR or PR after 6 cycles of the above regimen then the whole-brain radiotherapy (WBRT) was recommended; If patients achieved a CR or PR, auto-HSCT consolidation therapy was feasible; If the patient is not willing to transplant, enter single-agent oral Zanubrutinib to maintain until disease progression or intolerance.2. In group B, if patients who did not have a CR or PR after 6 cycles RLZT then the whole-brain radiotherapy (WBRT) was recommended, if patients achieved a CR or PR, maintain Zanubrutinib until diseaseprogression or intolerance. Results: The data cut-off date was June 30, 2022, totally 24 patients enrolled in this clinical trial，both groups had 12 patients(Table 1). The ORR in the 24 PCNSL pts was 79.2%, with 9 (37.5%) complete responses (CR) and 10 (41.7%) partial responses (PR), in addition, 2 (8.3%) stable disease (SD) and 3 (12.5%) progressive disease (PD) were observed. The ORR was 66.7% (CR:16.7%, PR 50%) in the RLZT+MTX group and 91.7% (CR:58.3%, PR 33.3%) in the RLZT group. The median PFS and OS were not achieved in total patients，and the estimated 18-months OS and PFS were 95.8% and 78.2%, respectively. Similarly, The median PFS and OS were not achieved in both groups，estimated 18-months OS was 91.7% in the RLZT+MTX group and 100% in the RLZT group. The estimated 18-months PFS was 81.5% in the RLZT+MTX group and 80% in the RLZT group (Figure1). Overall, 50%patients had experienced hematologic toxicity. Only 1 patient had grade ≥3 thrombocytopenia event and 1 patient had grade ≥3 leukopenia event. The overall incidence of non-hematologic toxicity was 50%, including gastrointestinal reactions, rash, liver and kidney damage, but only one patient had≥3 grade AE (rash). In addition, pneumonia was reported in 16.7% (4/24) of the patients, but no deaths were due to adverse events (Table 2). Conclusions: This study showed that RLZT+MTX was an effective and safety first-line treatment for PCNSL patients. It is worth noting that in elderly patients who cannot tolerate high-dose chemoradiotherapy, RLZT shows a promising prospect. Keywords: Primary central nervous system lymphoma, Zanubrutinib, first-line treatment Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Primary central nervous system lymphoma in the United States, 1975-2017.

Background:Primary central nervous system lymphoma (PCNSL) has received more attention because of an inferior prognosis. Less is known about the incidence rate, histological type, and survival rate of PCNSL, especially in the 2010s.Methods:Data of PCNSL from the Surveillance, Epidemiology, and End Results (SEER) registry database (SEER 9 registries and SEER 18 registries) were used. Incidence was estimated by age, gender, race, site, and histological type. Trends were analyzed using joinpoint regression and described as annual percent change (APC) and average annual percent change (AAPC). Five-year overall survival estimates were compared using log-rank tests.Results:Most PCNSL occurred in the brain, followed by the spinal cord. The most frequent histological type of PCNSL was diffuse large B-cell lymphoma, followed by marginal zone lymphoma. Incidence rate increased from 0.1/100,000 to 0.5/100,000 with an AAPC of 5.3% from 1975 to 2017. Incidence rates varied greatly between the younger and older age population. The 5-year overall survival rates in SEER 9 registries and SEER 18 registries were 30.5% and 37.4%, respectively. Even though the 5-year overall survival rate significantly increased from 27.9% for the 1975–1979 time period to 44.8% for the 2010–2017 time period, survival benefit could not be expected for patients ⩾60 years. The 5-year survival rate for elderly patients was about 30% in the 2010s.Conclusion:With aging, the incidence of PCNSL in the elderly is increased. Over the past decade, no advances have been made in the treatment of elderly PCNSL. Prospective trials with PCNSL are warranted to improve the survival of elderly patients.

Treatment of Primary CNS Lymphoma: Maximizing Clinical Benefit, Minimizing Neurotoxicity.

The optimal treatment for newly diagnosed and refractory or relapsed primary central nervous system lymphoma (PCNSL) is not fully defined. We review the epidemiology, clinical presentation, and current management strategies for newly diagnosed PCNSL as well as emerging treatments for refractory and relapsed disease. In recent decades, the incidence of PCNSL has increased in the elderly population. With advancements in chemotherapy for PCNSL, survival has improved. However, outcomes remain inferior when compared with other forms of extranodal lymphoma. Additionally, treatments can be associated with clinically significant neurotoxicities. Despite advances in the treatment of PCNSL, current treatment regimens remain suboptimal in terms of response rates and neurotoxicity. Well-tolerated agents, especially for the elderly, are still needed.

Diagnosis, prognosis and treatment of primary central nervous system lymphoma in the elderly population (Review).

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that is unique and different from systemic diffuse large B-cell lymphomas. The median age at diagnosis of PCNSL is 65 years and its incidence is rising rapidly in the elderly population. A total of ≥20% of all patients with PCNSL are ≥80 years old. Notably, age has been identified as an independent poor prognostic factor for PCNSL. Elderly patients have an inferior prognosis to that of younger patients and are more severely affected by iatrogenic toxicity; therefore, elderly patients represent a unique and vulnerable treatment subgroup. The present review summarized the available literature to provide an improved understanding of the epidemiology, clinical characteristics, diagnosis, prognosis and management of PCNSL in the elderly population. Notably, the incidence of PCNSL in immunocompetent elderly patients, predominantly in men, is increasing. For the diagnosis of CNSL, imaging-guided stereotactic biopsy is considered the gold standard. When stereotactic biopsy is not possible or conclusive, certain biomarkers have been described that can help establish a diagnosis. PCNSL has a very poor prognosis in the elderly, even though several prognostic scoring systems exist and several prognostic markers have been reported in patients with PCNSL. Furthermore, the treatment of elderly patients remains challenging; it is unlikely that a novel agent could be used as a curative monotherapy; however, a combination of novel agents with polychemotherapy or its combination with other novel drugs may have therapeutic potential.

Changing Incidence and Survival of Primary Central Nervous System Lymphoma in Australia: A 33-Year National Population-Based Study.

Primary central nervous system lymphoma (PCNSL) is a rare brain cancer that remains challenging to study. Epidemiology of PCNSL in the Australian population, which is racially and ethnically diverse, has not been examined previously. Using ICD-O-3.1 Morphology and Topography Codes to identify cases, we analyzed complete datasets from the comprehensive Australian Cancer Database (1982-2014, adults aged ≥ 20 years) to establish incidence rates and trends of PCNSL, and to define survival outcomes of individuals diagnosed with PCNSL, including the predominant diffuse large B-cell lymphoma (DLBCL) type. Age-standardized incidence of PCNSL increased by an average annual 6.8% percent over the study period, with current incidence of 0.43 (95% confidence interval, 0.41-0.46) per 100,000 person-years, in comparison to 21.89 (21.41-22.38) per 100,000 person-years for non-CNS lymphoma. Increase in incidence was characterized by an acute rise between 1996 and 1999, was more pronounced with increasing age, and was driven by increasing incidence of DLBCL. Overall survival for persons diagnosed with PCNSL improved significantly across the study period, with 5-year survival probability increasing from 0.21 (95% confidence interval, 0.16-0.26) to 0.33 (0.30-0.36), and median survival increasing from 318 to 600 days, between 1982-1999 and 2000-2014. Increase in survival was significantly higher for persons with DLBCL versus non-DLBCL PCNSL, but substantially lower than that for persons with non-CNS lymphoma, who had a 5-year survival probability of 0.62 (0.62-0.62) and a median survival of 3388 days in 2000-2014. This study links increasing incidence of PCNSL in Australia to increasing incidence of DLCBL, including in younger adults, and highlights the improving, but low, survival outcome of this cancer.

Hemorrhagic Attitude in Frameless and Frame-Based Stereotactic Biopsy for Deep-Seated Primary Central Nervous System Lymphomas in Immunocompetent Patients: A Multicentric Analysis of the Last Twenty Years

Primary central nervous system lymphoma (PCNSL) is a rare manifestation of aggressive extranodal non-Hodgkin lymphoma. In patients with deep-seated lesions, stereotactic brain biopsy (SBB) is an accepted diagnostic procedure to obtain histopathologic confirmation. The aim of this study was to assess the feasibility, diagnostic yield, safety, and complications of stereotactic procedures in midline and deep-seated PCNSLs. Patients selected had received a histopathologic diagnosis of PCNSL localized in deep-seated midline structures, obtained by SBB. The intraoperative frozen section was executed as an integral part of the procedure. Computed tomography scan was performed after surgery. A total of 476 SBBs were performed between January 2000 and December 2019 . Of these SBBs, 91 deep-seated lesions had a histologic diagnosis of PCNSL. A significant increase of the incidence of PCNSL compared with all other diseases was observed (P < 0.0001). Eight patients (8.7%) showed a symptomatic hemorrhage, 4 of whom required craniotomy. There were 4 deaths and 2 cases of permanent morbidity. The hemorrhage risk in the PCNSL group was statistically significant (P= 0.0003) compared with other histotypes. In suspected cases of PCNSL, a histopathologic diagnosis is necessary to distinguish it from glioblastoma or other, nonmalignant conditions. Deep-seated PCNSLs present a higher risk of biopsy-related morbidity and mortality. Intraoperative frozen section increases the diagnostic yield and reduces the number of sampling procedures. Postoperative computed tomography seems to be warranted in patients with suspected PCNSL.

IMMU-50. BBB CROSSING NANO-IMMUNOMEDICINE COMBINATION THERAPY TO TREAT BRAIN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

Abstract INTRODUCTION Lack of standard treatment of Primary Central Nervous System Lymphoma (PCNSL) was acknowledged in phase III intergroup study (HOVON 105/ALLG NHL 24). PCNSL incidence is increasing for unknown reasons, particularly among persons over 65 years. One of the major limitations of successful treatment of PCNSL is the blood-brain barrier (BBB), which prevents drug delivery into the brain. METHODS Polymer nanoconjugate based on biodegradable poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) was used for treatment of BALB/C mice with intracranially inoculated murine A20 lymphoma. PHPMA-based nanoconjugates have defined synthesis strategy for BBB transcytosis, tumor targeting, and cancer cell killing. Nano immunodrug PHPMA/AP-2/Fab’/c-Myc inhibitor/H6 conjugate contains multiple AP-2 peptides for efficient delivery across the BBB and Fab’ fragments of αCD20 mouse Ab for CD20 receptor crosslinking on PCNSL cells. c-Myc inhibitor bound via a disulfide bond is transferred to the cytoplasm followed by cleavage. The therapeutic efficacy and survival were evaluated together with spectral flow cytometry and RNA-seq bioinformatic analysis of tumor tissues. RESULTS Nanoconjugates were able to penetrate BBB and accumulate in brain parenchyma. The best survival results were obtained for the group where nanoconjugate with αCD20 Fab’ causing tumor cell apoptosis and c-Myc antisense inhibitor was combined with αPD-1 checkpoint inhibitor. Survival compared to PBS-treated controls was significant (P=0.0006 by ANOVA). Ex vivo analysis of A20 brain lymphoma tissue after treatment with nanoconjugates demonstrated reduction of Tregs, associated with downregulation of IL-10 and IL-1β in plasma. Spectral flow cytometry revealed activation of tumor infiltrating T lymphocytes and M1 macrophages in lead nanodrug treated groups. RNA-seq data correlated with flow cytometry results indicating the activation of genes linked to IFN-γ pathway important for anti-tumor response and M1 macrophage activation. Immunostaining confirmed a marked increase of M1-specific iNOS expression in the nanodrug-treated tumors. Support: NIH grants: R01 CA188743, R01 CA206220, R01 CA209921

Abstract 2869: Nano-immuno combination therapy to treat brain primary central nervous system lymphoma

Abstract Purpose: Lack of standard treatment of Primary Central Nervous System Lymphoma (PCNSL) was acknowledged in phase III intergroup study (HOVON 105/ALLG NHL 24). PCNSL incidence is increasing for unknown reasons, particularly among persons over 65 years of age. The major limitation of successful treatment of PCNSL is the blood-brain barrier (BBB), which prevents drug delivery into the brain. Our novel treatment employs nano immunoconjugates (NICs) that cross BBB and activate brain lymphoma immunity. These NICs specifically block c-Myc expression and induce CD20 crosslinking. The NICs, in combination with αPD1, were systemically delivered to the lymphoma mice and this treatment led to a local and systemic broad-spectrum immune response by activation of IFN-γ that is an important anti-tumor M1 macrophage activator. Methods: Polymer nanoconjugate based on biodegradable poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA)-P was used for treatment of BALB/C mice with intracranially inoculated murine A20 lymphoma. PHPMA-based nanoconjugates have defined synthesis strategy for BBB transcytosis, tumor targeting, and cancer cell killing. Nano-immunodrug P/AP-2/CD20 Fab'or c-Myc inhibitor (anti-sense oligonucleotides)/H6 conjugate contains multiple AP-2 peptides for efficient delivery across the BBB and Fab' fragments of αCD20 Ab (mouse specific) for CD20 receptor crosslinking on PCNSL cells. c-Myc inhibitor bound via a disulfide bond is transferred to the cytoplasm followed by cleavage; this is facilitated by (His)6 peptide-mediated endosome disruption. The nanoconjugate was examined for the ability to cross BBB in vivo by live imaging. The therapeutic efficacy and survival were evaluated together with spectral flow cytometry (FC) and RNA-seq bioinformatic analysis of tumor tissues. Results: NIC was able to penetrate BBB and accumulate in brain parenchyma. The best survival results were obtained from the combination groups with CD20 Fab' crosslinking CD20 receptors resulting in apoptosis and c-Myc antisense inhibition in combination with αPD-1 checkpoint inhibitor. Survival compared to PBS-treated controls was significant (P=0.0006, P=0.0034, respectively, by ANOVA). FC analysis of A20 brain lymphoma tissue after treatment with NICs demonstrated reduction of Tregs, associated with downregulation of IL-10 and IL-1β in plasma. Spectral flow cytometry revealed activation of tumor infiltrating T lymphocytes and the M1 macrophages in lead treatment groups. RNA-seq data correlated with flow cytometry results indicating the activation of genes linked to IFN-γ pathway important for anti-tumor response and M1 macrophage activation. Immunostaining confirmed a marked increase of M1-specific iNOS expression in the nanodrug-treated tumors. Conclusion: The PCNSL treatment results demonstrate for the first time that the BBB delivery of NICs modified brain tumor microenvironment and activated brain local immune system though modulation of T cells and IFN-γ pathway. Support: NIH grants: R01 CA188743, R01 CA206220, R01 CA209921 Citation Format: Tao Sun, Ekaterina Shatalova, Oliver Braubach, Dmytro Klymyshyn, Eggehard Holler, Jiawei Wang, Lian Li, Jiyuan Yang, Jindrich Kopecek, Julia Y. Ljubimova. Nano-immuno combination therapy to treat brain primary central nervous system lymphoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2869.

Primary central nervous system lymphoma: status and advances in diagnosis, molecular pathogenesis, and treatment

Primary central nervous system lymphoma (PCNSL) is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes. This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients. The authors retrieved information from the PubMed database up to September 2019. The annual incidence of PCNSL increased over the last four decades. The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate, which is now the backbone of all first-line treatment polychemotherapy regimens. Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-κB, B cell antigen receptor, and Janus kinases/signal transducer and activator of transcription proteins signal pathways. Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy. In particular, lenalidomide and ibrutinib have demonstrated durable efficiency. Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups, but there is still room to improve outcome by optimizing current chemotherapy and novel agents.

Current status and progress in treatment of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare extranodal aggressive non-Hodgkin lymphoma (NHL) that differs from other NHL in terms of morbidity, diagnosis, and treatment. PCNSL accounts for 1%-6% of all central nervous system tumors, and 4%-6% of extranodal lymphomas. The incidence of PCNSL has increased gradually in the past 10 years, from 0.15/100 000 to 0.48/100 000. The pathological diagnosis is the only method for definite diagnosis. Stereotactic puncture is the currently preferred invasive procedure. Magnetic resonance imaging is the gold standard for diagnosis and follow-up of PCNSL. The chemotherapy based on large doses of methotrexate (≥3 g/m2) is currently the main treatment. For patients who are suitable for autologous hematopoietic stem cell transplantation, autologous transplantation can improve the short-term and long-term survival. New drug treatment and clinical research are encouraged for patients with relapsed and refractory PCNSL. This review will briefly introduce the current status and progress in treatment of PCNSL. Key words: Lymphoma; Central nervous system; Drug therapy, combination

Increased Serum Beta-2 Microglobulin during Induction Chemotherapy Associated with Poor Prognosis in Primary Central Nervous System Lymphoma

Introduction Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma that exclusively involves the brain, leptomeninges, eyes, or spinal cord. Due to the rare incidence of PCNSL, therapeutic decisions and predictions of outcomes rely on phase 2 clinical trials and retrospective studies. Indeed, it is important to continuously search potential prognostic factors. Serum beta-2 microglobulin (B2MG) is thought to be associated with prognosis in several lymphomas and multiple myeloma. Previous study in our center showed that increased serum B2MG of ≥ 1.8 μg/mL at diagnosis was associated with poor prognosis in PCNSL. In this study, we investigated association of serum B2MG level changes with survival outcomes in PCNSL patients during induction chemotherapy who had elevated serum B2MG level at diagnosis.Methods We retrospectively reviewed prospectively collected PCNSL registry data for patients treated from March 1993 to May 2017 at Asan Medical Center in Seoul, Korea. Patients with serum B2MG of ≥ 1.8 μg/mL at diagnosis who had at least two or more measurement of serum B2MG including at diagnosis, 6 weeks, and 3 months from the initiation of induction chemotherapy were included in the analysis. Two weeks of window period was allowed for measured B2MG at 6 weeks and 3 months from the beginning of treatment. Overall survival (OS) was defined as the time from the initiation of induction treatment to death from any cause, and progression-free survival (PFS) was defined as the time from the initiation of induction treatment to disease progression or death. Univariate analyses were performed to compare survival outcomes using log-rank tests. Multivariate analyses were performed to identify independent prognostic factors for PFS and OS using a Cox proportional hazards model.Results Among 241 patients with diagnosis of PCNSL, 42 patients were included in the study. Median follow-up period was 4.0 years (range, 0.1-9.7). Median OS and PFS was 2.3 years (95% CI 1.9-2.6), and 1.2 years (95% CI 0.6-1.8), respectively. Median age was 67 years old (range, 28-85) and 26 patients (61.9%) were male. All patients received methotrexate-based combination chemotherapy as induction treatment and 31 patients (88.6%) showed complete response or partial response as best responses. Ten patients (23.8%) received consolidation treatment with high-dose chemotherapy followed-by autologous stem cell transplantation. Patients were classified into two groups according to serum B2MG level difference compared to B2MG level at diagnosis with the B2MG level at 6 weeks and 3 months from the initiation of induction treatment. Median B2MG at diagnosis, 6 weeks, and 3 months was 2.4 μg/mL (range, 1.9-11.7), 2.5 μg/mL (range, 1.3-8.7), and 2.6 μg/mL (range, 1.4-8.7), respectively. There was no statistically significant difference in terms of OS between patients with increased B2MG level at 6 weeks (16 patients) and patients with no increment (10 patients) with median OS of 1.4 years (95% CI 0.1-2.8) and 3.0 years (95% CI 1.1-4.9), respectively (P = 0.065). Patients with increased B2MG level at 3 months (23 patients) significantly poor prognosis in terms of OS compared to patients with same or decreased level (13 patients). Median OS was 1.4 years (95% 0.6-2.3) for the increased patients and not reached in patients with no increment (P < 0.001). Multivariate analysis with other factors showed significantly poor outcomes in patients with increased serum B2MG level at 3 months from the initiation of induction treatment in terms of OS with hazard ratio of 14.3 (95% CI 2.1-100.0, P = 0.007).Conclusion Among PCNSL patients who had serum B2MG level of ≥ 1.8 μg/mL at diagnosis, which was associated with poor prognosis in our previous study, patients with no increment of serum B2MG level at 3 months from the initiation of induction chemotherapy was associated with better survival outcomes in terms of OS compared to those with increased level. DisclosuresNo relevant conflicts of interest to declare.

Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000-2013.

This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000-2013 in Sweden. Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100000 person-years and 95% confidence intervals (CI) were calculated, and PCNSL-specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison. With 359 identified PCNSL cases (median age 66years), overall incidence was 0.26 (95% CI: 0.24-0.29) and the average annual increase 4% (P=.002). The increasing trend was primarily observed among elderly individuals (70+years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6years after diagnosis. The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population-based setting, although the presence of long-term survivors among fit patients is encouraging.

The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades.

There has been significant improvement in treatment outcomes of primary central nervous system lymphoma (PCNSL) at specialized centers over the past several decades; however, it is unclear if these changes have translated to benefits in the general population. In this study, we utilized 2 national databases to examine survival trends over time for PCNSL: the Central Brain Tumor Registry of the United States (CBTRUS, 2000-2013) and 18 registries from the Surveillance, Epidemiology, and End Results program (SEER, 1973-2013). The annual incidence of PCNSL in 2013 was 0.4 per 100000 population (CBTRUS/SEER). Incidence increased from 0.1 per 100000 in the 1970s to 0.4 per 100000 in the 1980s, correlating with an increase in the diagnosis of patients ≥70 years (1973: 0.2 vs 2013: 2.1 [SEER]). Incidence rates differed greatly between young and elderly patients (age 20-29 y: 0.08 vs 70-79 y: 4.32 [CBTRUS]). Even though the median overall survival of all patients doubled from 12.5 months in the 1970s to 26 months in the 2010s, this survival benefit was limited to patients <70 years. Survival in the elderly population has not changed in the last 40 years (6 mo in the 1970s vs 7 mo in the 2010s, P = 0.1). The poor outcome seen in the particularly vulnerable elderly patient population highlights the need for clinical trials targeting the elderly in hopes of improving treatment strategies and survival.

Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients.

Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed human immunodeficiency virus-infected people. Using data from the US transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288 029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio=65.1; N=168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N=2043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio [aIRR]=0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR=2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non-Hispanic whites (aIRR=2.09); after induction immunosuppression with alemtuzumab (aIRR=3.12), monoclonal antibodies (aIRR=1.83), or polyclonal antibodies (aIRR=2.03); in recipients who were Epstein-Barr virus-seronegative at the time of transplant and at risk of primary infection (aIRR=1.95); and within the first 1.5years after transplant. Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio [aHR]=11.79) or graft failure/retransplantation (aHR=3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR=1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis.

Changes in survival of primary central nervous system lymphoma based on a review of national databases over 40 years.

2040 Background: There has been significant improvement in treatment outcomes of Primary Central Nervous System Lymphoma (PCNSL) at specialized centers over past decades, and it is unclear if these changes have translated to benefits in the general population. In this study, we utilized national databases to examine survival trends over time. Methods: Incidence rates were obtained from the Central Brain Tumor Registry of the United States (CBTRUS, 2000 – 2013) and 18 Surveillance, Epidemiology and End Results (SEER, 1973 – 2013) registries. Data for survival analysis was obtained from SEER and analyzed using SEER*STAT. To focus on non-HIV-associated PCNSL, patients with “other infectious and parasitic diseases including HIV” as cause of death and follow up were excluded. CBTRUS identified 19,027 patients over 13 years and SEER 6,765 over 40 years. Results: The annual incidence of PCNSL in 2013 was 0.4 per 100,000 population (CBTRUS/SEER). Incidence increased from 0.1 per 100,000 in the 1970s to 0.4 per 100,000 in the 1980s, correlating with an increase in the diagnosis of elderly patients, ≥70 (1973:0.2 vs 2013:2.1 – SEER). Incidence rates differed greatly between young and elderly patients (20-29: 0.08 vs 70-79: 4.32 – CBTRUS). The median overall survival (mOS) of all patients is 17 months (m) with no survival benefit based on sex. Survival doubled from 12.5 m in the 1970s to 26 m in the 2010s. There was a significant difference in survival based on age: &lt; 50: 83 m vs 50-69: 25 m vs ≥70: 6 m (p-value &lt; 0.0001). In patients &lt; 50, mOS increased from 35.5 m in the 1970s to 134 m in the 2000s (mOS not achieved in 2010s). In patients 50-69, mOS increased from 8 m in the 1970s to 35 m in the 2010s. However, mOS in the elderly population, ≥70, has not changed in the last 40 years (6 m in the 1970s vs 7 m in the 2010s, p-value = 0.1). Conclusions: PCNSL is a disease that more frequently affects the elderly. Although overall survival has increased over the past 4 decades, reflecting current literature in PCNSL, survival in the elderly has not changed since the 1970s. Identification of this vulnerable patient population highlights the need for clinical trials targeting the elderly in hopes of improving treatment strategies and ultimately outcomes.

Advances in the treatment of newly diagnosed primary central nervous system lymphomas.

Primary central nervous system lymphoma (PCNSL) is a type of highly invasive non-Hodgkin lymphoma. With a growing number of organ transplantation and immunosuppressant therapy, the incidence of PCNSL has been growing rapidly in recent years, which is attributed to the increased incidence of HIV/AIDS, a prominent risk factor for developing PCNSL. The rising rate of PCNSL incidence is the highest among the intracranial tumors. In the past 20 years, dozens of clinical trials related to PCNSL have been registered, but adequate therapeutics are still challenging. Currently, the chemotherapy regimens based on high-dose methotrexate and whole-brain radiotherapy are the two main therapeutic options; however, the toxicity associated with those is the main problem that challenges medical researchers. Novel agents and therapeutic strategies have been developed in recent years. In the current review, we describe advances in the treatment of PCNSL and discuss novel therapeutic approaches currently in development, such as the use of rituximab, disruption of the blood-brain barrier, and state-of-the-art radiotherapy.

Primary central nervous system lymphomas.

Primary central nervous system lymphoma (PCNSL) is an aggressive B cell lymphoma that occurs in immunocompetent and immunosuppressed patients. Primary ocular lymphoma represents an important variant of this disease. The outcome for patients with PCNSL is rapidly improving with new treatment strategies. This review focuses on recent advances, investigations, and controversies in the management of these increasingly important malignancies. The incidence of PCNSL is rising in immunocompetent patients over the age of 60 years for unexplained reasons. However, the incidence of AIDS-related PCNSL, which is related to Epstein-Barr virus infections, has fallen with the institution of highly active antiretroviral therapy. During the past decade, standard therapy has evolved from cranial irradiation to high dose methotrexate-based regimens. This shift in therapy has been associated with an increase in the median survival of patients from 1 year to longer than 3 years, and with an equally striking reduction in neurotoxicity if whole brain radiation is avoided. Optimal therapeutic results require careful attention to opportunistic infections, thromboembolic disease, and renal toxicities associated with high dose methotrexate. Overall, PCNSLs are increasing in frequency and the results of therapy for this disease have dramatically improved during the past decade. Many important therapeutic questions remain unanswered. These include the optimal dose, frequency, and duration of methotrexate, as well as the roles of additional systemic chemotherapy drugs, intrathecal therapy, and cranial irradiation. Further progress in this uncommon disease will depend on entering patients into carefully designed multicenter clinical trials to build upon the significant advances that have been made.

OT-06 * MULTICENTRIC PRIMARY CENTRAL NERVOUS SYSTEM DIFFUSE LARGE B CELL LYMPHOMA IN AN INMUNOCOMPETENT ADOLESCENT, CASE REPORT

BACKGROUND: Primary central nervous system lymphoma (PCNSL) accounts for 4 to 7% of all primary intracranial neoplasms and 1 to 2% of all lymphomas. PCNSL incidence has increased tenfold over the last three decades in both immunocompetent and immunocompromised individuals. CASE REPORT: We present the case of a female adolescent with no risk factors for immunosuppression. Her immunological profile was normal. Her main symptom was headache two years before being diagnosed with a primary central nervous system diffuse large b cell lymphoma. Left ptosis, facial paralysis, disarthria and diplopia appeared one year later. She developed paresthesias in both hands with loss of strength. One month before she had seizures. In the magnetic resonance a multilobulated heterogeneous mass in left ventricule was found with high contrast enhancement. In spinal cord at C1-C2, an intramedular heterogeneous lesion was also observed. Stereotactic biopsy was done reporting CD20+ primary central nervous system diffuse large b cell lymphoma with reactive gliosis. Cerebrospinal fluid was negative. No viral association was detected. DISCUSSION: PCNSL are a rare malignant neoplasm in pediatric age, and more common in male. Worldwide, near fourteen cases are diagnosed each year. Most of these cases appear in immunocompromised patients. This is a special case because of the association of lymphoma in an immunocompetent girl. Clinical features differs in the evolution time which is longer than expected for a lymphoma. Radiological imaging suggests a multicentric presentation or a previous non-diagnosed disease. These cases suggests that lymphoma have a different clinical, radiological and histological presentation when the localization is in central nervous system. Malignant tumors have a non-predictable evolution in this tissue. Do we have to treat it in the same way?