Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Is There an Indication for First Line Radiotherapy in Primary CNS Lymphoma?

ABSTRACT: Background: Primary CNS Lymphoma is a rare and severe but potentially curable disease. In the last thirty years treatment has changed significantly. Survival times increased due to high-dose methotrexate-based chemotherapy. With intensive regimens involving autologous stem cell transplantation (ASCT), 4-year survival rates of more than 80% can be reached. However, this treatment regimen is not feasible in all patients, and is associated with some mortality. Methods: In this review, current evidence regarding the efficacy and toxicity of radiotherapy in PCNSL shall be summarized and discussed mainly based on data of controlled trials. Results: Being the first feasible treatment whole brain radiotherapy (WBRT) was initially used alone, and later as a consolidating treatment after high-dose methotrexate-based chemotherapy. More recently, concerns regarding activity and neurotoxicity of standard dose WBRT limited its use. On the contrary, latest evidence of some phase II trials suggests efficacy of consolidating WBRT is comparable to ASCT. After complete remission reduced dose WBRT appears as a feasible concept with decreased neurotoxicity. Evidence for use of local stereotactic radiotherapy is very limited. Conclusion: Radiotherapy has a role in the treatment of PCNSL patients not suitable to ASCT, e.g., as consolidating reduced dose WBRT after complete response. Local stereotactic radiotherapy for residual disease should be examined in future trials.

SUBMITTER: Seidel C

PROVIDER: S-EPMC8197540 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Primary CNS Lymphoma.

Project description:Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. To our knowledge, no randomized trial has been conducted for recurrent/refractory disease, leaving many questions unanswered about optimal first-line and salvage treatments. This review will give an overview of the presentation, evaluation, and treatment of immunocompetent patients with PCNSL.

| S-EPMC5516483 | biostudies-literature

Primary CNS lymphoma.

Project description:Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system is an aggressive malignancy that exhibits unique biological features and characteristic clinical behaviour, with overall long-term survival rates of around 20-40%. Clinical outcome has improved following the advent of chemoradiation protocols incorporating high-dose methotrexate in the mid-1980s, but disease relapse and adverse neurocognitive sequelae remain major clinical challenges. To address this, investigators have focused on improving drug therapy with novel cytotoxic combinations, monoclonal antibody therapy, and intensive chemotherapy consolidation approaches, in an attempt to improve disease control whilst reducing the requirement for whole-brain radiotherapy. Outcomes for patients that are older, immunocompromised, or have relapsed/refractory disease remain unsatisfactory and there is a paucity of clinical trial data to guide treatment of these groups. This review highlights recent advances in pathobiology, imaging, and clinical management of PCNSL and looks ahead to research priorities for this rare and challenging lymphoid malignancy.

| S-EPMC4180029 | biostudies-literature

Beyond high-dose methotrexate and brain radiotherapy: novel targets and agents for primary CNS lymphoma.

Project description:BACKGROUND:While there has been significant progress in outcomes for patients diagnosed with primary central nervous system (CNS) lymphoma (PCNSL), survival rates will likely plateau with the current armamentarium of agents used to treat these patients. Moreover, given that PCNSL increasingly impacts an older population, a significant proportion of patients are not eligible for intensive therapies such as high-dose chemotherapy or whole-brain radiation. There is a need for the development of novel agents, which target key survival pathways in order to continue to make progress in this disease. PATIENTS AND METHODS:We reviewed the key molecular pathways and genomic aberrations in PCNSL in order to identify candidate targets. We focused on molecules and pathways that have been identified and confirmed by more than one investigator or methodology. RESULTS:While PCNSL tumors usually express a BCL6+, MUM1+ 'activated, germinal center' immunophenotype, they exhibit multiple shared genetic properties with ABC-type diffuse large B-cell lymphomas. Candidate targets and pathways include NFkB, the B-cell receptor, the JAK/STAT pathway, IRF4, BCL-6 as well as PIM kinases. Elements of the tumor microenvironment that may be exploited therapeutically include chemokine pathways, as well as macrophage and T-cell responses. CONCLUSIONS:There is a significant need for developing novel therapies in PCNSL, given that an increasing proportion of patients are not eligible for high-dose chemotherapy and brain radiation is associated with detrimental cognitive side-effects. We provide an overview of potential drug targets and novel agents that may be integrated with existing strategies in order to make further progress in this disease.

| S-EPMC3905778 | biostudies-literature

Improving outcomes in primary CNS lymphoma.

Project description:Primary central nervous system lymphoma (PCNSL) is an aggressive disease with previously poor prognosis. The advent of high-dose methotrexate-based induction regimens as well as use of consolidation therapy has greatly improved this prognosis in recent decades, but durable remission still eludes half of patients. In this review, we summarize the progress made in the treatment of PCNSL as well as the challenges that remain, with a focus on defining optimal induction and consolidation regimens, including the promise of developing biotherapies. Future studies will help delineate the best combination of existing and novel treatment strategies, with the goal of expanding the cohort of patients achieving a cure.

| S-EPMC10481403 | biostudies-literature

Sex-Specific Differences in Primary CNS Lymphoma.

Project description:Sex-specific differences have been increasingly recognized in many human diseases including brain cancer, namely glioblastoma. Primary CNS lymphoma (PCNSL) is an exceedingly rare type of brain cancer that tends to have a higher incidence and worse outcomes in male patients. Yet, relatively little is known about the reasons that contribute to these observed sex-specific differences. Using a population-representative cohort of patients with PCNSL with dense magnetic resonance (MR) imaging and digital pathology annotation (n = 74), we performed sex-specific cluster and survival analyses to explore possible associations. We found three prognostically relevant clusters for females and two for males, characterized by differences in (i) patient demographics, (ii) tumor-associated immune response, and (iii) MR imaging phenotypes. Upon a multivariable analysis, an enhanced FoxP3+ lymphocyte-driven immune response was associated with a shorter overall survival particularly in female patients (HR 1.65, p = 0.035), while an increased extent of contrast enhancement emerged as an adverse predictor of outcomes in male patients (HR 1.05, p < 0.01). In conclusion, we found divergent prognostic constellations between female and male patients with PCNSL that suggest differential roles of tumor-associated immune response and MR imaging phenotypes. Our results further underline the importance of continued sex-specific analyses in the field of brain cancer.

| S-EPMC7352658 | biostudies-literature

Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma.

Project description:BackgroundWe investigated the prognostic significance of B-cell differentiation status and common B-cell differentiation markers in a post hoc analysis of 119 patients with primary CNS lymphoma (PCNSL) homogeneously receiving high-dose methotrexate (HDMTX)-based chemotherapy within the prospective G-PCNSL-SG1 trial.MethodsWe evaluated protein expression of B-cell lymphoma 2 (BCL2), BCL6, CD10, and multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) by immunohistochemistry and analyzed the association with survival.ResultsThe median follow-up of all patients was 67.5 months. Median progression-free survival (PFS) was 10.61 months (95% CI: 4.23-17.00). Median overall survival (OS) was 28.85 months (95% CI: 17.96-39.73). Eighty-nine tumors expressed BCL2 (92.7%), 24 (20.5%) expressed CD10, 60 (54.1%) expressed BCL6, and 87 (79.0%) expressed MUM1/IRF4. On the basis of the Hans algorithm, 80 tumors (73.4%) were classified to the non-germinal center B group, suggesting a post-germinal center origin of PCNSL. Expression of BCL6 (cutoff point 30%), but none of the other markers, was associated with shorter PFS (P = .047) and OS (P = .035). On multivariate analysis, BCL6 expression was associated with shorter PFS (hazard ratio: 1.95, 95% CI: 1.22-3.12, P = .005) but not OS (hazard ratio: 1.85, 95% CI: 0.71-4.80, P = .21). Classification according to Hans algorithm and expression status of the single B-cell markers BCL2, CD10, and MUM1/IRF4 did not correlate with prognosis.ConclusionThe findings are limited by the fact that only 23% of all G-PCNSL-SG1 patients could be included in the analysis. If validated in an independent cohort, BCL6 may assume clinical relevance as an unfavorable prognostic biomarker in PCNSL.

| S-EPMC5654355 | biostudies-literature

Gene expression and angiotropism in primary CNS lymphoma.

Project description:Primary CNS lymphoma is an aggressive form of non-Hodgkin lymphoma whose growth is restricted to the central nervous system. We used cDNA microarray analysis to compare the gene expression signature of primary CNS lymphomas with nodal large B-cell lymphomas. Here, we show that while individual cases of primary CNS lymphomas may be classified as germinal center B-cell, activated B-cell, or type 3 large B-cell lymphoma, brain lymphomas are distinguished from nodal large B-cell lymphomas by high expression of regulators of the unfolded protein response (UPR) signaling pathway, by the oncogenes c-Myc and Pim-1, and by distinct regulators of apoptosis. We demonstrate that interleukin-4 (IL-4) is expressed by tumor vasculature as well as by tumor cells in CNS lymphomas. We also identify high expression in CNS lymphomas of several IL-4-induced genes, including X-box binding protein 1 (XBP-1), a regulator of the UPR. In addition, we demonstrate expression of the activated form of STAT6, a mediator of IL-4 signaling, by tumor cells and tumor endothelia in CNS lymphomas. High expression of activated STAT6 in tumors was associated with short survival in an independent set of patients with primary CNS lymphoma who were treated with high-dose intravenous methotrexate therapy.

| S-EPMC1895776 | biostudies-literature

Expression of Tim-1 in primary CNS lymphoma.

Project description:Primary central nervous system lymphoma (PCNSL) is a distinct subtype of extranodal lymphoma with aggressive clinical course and poor outcome. As increased IL-10/IL-6 ratio is recognized in the cerebrospinal fluid (CSF) of PCNSL patients, we hypothesized that PCNSL might originate from a population of B cells with high IL-10-producing capacity, an equivalent of "regulatory B cells" in mice. We intended in this study to clarify whether Tim-1, a molecule known as a marker for regulatory B cells in mice, is expressed in PCNSL. By immunohistochemical analysis, Tim-1 was shown to be positive in as high as 54.2% of PCNSL (26 of 58 samples), while it was positive in 19.1% of systemic diffuse large B-cell lymphoma (DLBCL) samples (17 of 89 samples; P < 0.001). Tim-1 expression positively correlated with IL-10 expression in PCNSL (Cramer's V = 0.55, P < 0.001), and forced expression of Tim-1 in a PCNSL cell line resulted in increased IL-10 secretion, suggesting that Tim-1 is functionally linked with IL-10 production in PCNSL. Moreover, soluble Tim-1 was detectable in the CSF of PCNSL patients, and was suggested to parallel disease activity. In summary, PCNSL is characterized by frequent Tim-1 expression, and its soluble form in CSF may become a useful biomarker for PCNSL.

| S-EPMC5119979 | biostudies-literature

Primary CNS lymphoma commonly expresses immune response biomarkers.

Project description:BackgroundPrimary central nervous system lymphoma (PCNSL) is rare and there is limited genomic and immunological information available. Incidental clinical and radiographic responses have been reported in PCNSL patients treated with immune checkpoint inhibitors.Materials and methodsTo genetically characterize and ascertain if the majority of PCNSL patients may potentially benefit from immune checkpoint inhibitors, we profiled 48 subjects with PCNSL from 2013 to 2018 with (1) next-generation sequencing to detect mutations, gene amplifications, and microsatellite instability (MSI); (2) RNA sequencing to detect gene fusions; and (3) immunohistochemistry to ascertain PD-1 and PD-L1 expression. Tumor mutational burden (TMB) was calculated using somatic nonsynonymous missense mutations.ResultsHigh PD-L1 expression (>5% staining) was seen in 18 patients (37.5%), and intermediate expression (1-5% staining) was noted in 14 patients (29.2%). Sixteen patients (33.3%) lacked PD-L1 expression. PD-1 expression (>1 cell/high-power field) was seen in 12/14 tumors (85.7%), uncorrelated with PD-L1 expression. TMB of greater than or equal to 5 mutations per megabase (mt/Mb) occurred in 41/42 tumors, with 19% (n = 8) exhibiting high TMB (≥17 mt/Mb), 71.4% (n = 30) exhibiting intermediate TMB (7-16 mt/Mb), and 9.5% (n = 4) exhibiting low TMB (≤6 mt/Mb). No samples had MSI. Twenty-six genes showed mutations, most frequently in MYD88 (34/42, 81%), CD79B (23/42, 55%), and PIM1 (23/42, 55%). Among 7 cases tested with RNA sequencing, an ETV6-IGH fusion was found. Overall, 18/48 samples expressed high PD-L1 and 38/42 samples expressed intermediate to high TMB.ConclusionsBased on TMB biomarker expression, over 90% of PCNSL patients may benefit from the use of immune checkpoint inhibitors.

| S-EPMC7067145 | biostudies-literature

Primary CNS Lymphoma: Progress With Dose-Intensive Consolidation.

Project description:The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

| S-EPMC9649280 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data