The aim of this study was to compare prognostic factors and survival outcomes in patients with primary central nervous system lymphoma (PCNSL).

The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed with PCNSL between 2000 and 2019.

Between 2000 and 2019, a total of 5,812 patients were diagnosed with PCNSL, of whom 2,175 (37%) were ≤ 60 years old and 3,637 (63%) were >60 years old. The younger patients had a higher rate of being diagnosed with stage I-II, a higher rate of receiving chemotherapy and radiotherapy, a similar rate of receiving surgery, and a longer survival time. The most common histological subtype among PCNSL patients was diffuse large B-cell lymphoma (PCNS-DLBCL). Younger PCNS-DLBCL patients who received surgery and chemotherapy exhibited significantly improved overall survival (OS) and disease-specific mortality (DSM) and that African American patients were associated with poorer OS and DSM. Older patients receiving surgery, chemotherapy, and radiotherapy exhibited significantly improved OS and DSM, male and higher Ann Arbor stage were associated with poorer OS and DSM. We created a nomogram for PCNS-DLBCL to predict OS, with a C-index of 0.6749 in the younger cohort and 0.6676 in the older cohort. In the combined therapy analysis, chemotherapy combined with surgical resection had better OS and DSM in all patients.

The two age-stratified cohorts significantly differed in terms of OS and independent influences on OS and DSM. Our constructed nomogram exhibited high accuracy in predicting OS in PCNS-DLBCL patients.

Different from typical primary central nervous system lymphoma (PCNSL), early-stage atypical PCNSL usually presents as patchy signal abnormalities without evident mass effect or significant contrast enhancement and is prone to confusion with low-grade glioma (LGG). This study aims to develop a magnetic resonance imaging (MRI)-based radiomics model to differentiate early-stage atypical PCNSL from LGG.

Two cohorts consisting of early-stage atypical PCNSL patients, as well as LGG patients with similar radiological manifestations, were retrospectively recruited from West China Hospital of Sichuan University (PCNSL = 75; LGG = 138) and Chengdu Shangjin Nanfu Hospital (PCNSL = 35; LGG = 72) to serve as the training set and external validation set, respectively. Within the training set, there were additional early-stage atypical lesions from 19 typical or advanced-stage PCNSL patients included as a supplement. MRI-based radiomics models were developed and validated based on these 2 cohorts.

Nine radiomic features were selected as significant features, most of which are wavelet radiomic features. The best radiomics model achieved an area under the curve of 0.929 (0.901-0.957) and an accuracy of 91.6% on the independent external validation set. The inclusion of 19 additional PCNSL patients improved the model's performance.

The MRI-based radiomics model can accurately differentiate early-stage atypical PCNSL from LGG with similar radiological manifestations, allowing early-stage atypical PCNSL patients to receive timely and appropriate radiotherapy or chemotherapy while avoiding unnecessary surgical resection.

Background/Objectives: The management of primary central nervous system lymphoma (PCNSL) has traditionally prioritized diagnostic biopsy, with surgical resection often considered secondary due to risks and potential bias in previous studies, which included patients with deep or multiple tumors. This study aims to evaluate the impact of surgical resection on survival in patients with solitary, resectable PCNSL. Methods: We conducted a retrospective analysis of PCNSL patients treated via brain biopsy or surgical resection at our institution between January 2010 and December 2022. Cases with deep-located tumors (corpus callosum, basal ganglia, thalamus, and brainstem) or multiple lesions were excluded. Survival and clinical outcomes were compared between the two groups. Results: A total of 79 patients (30 resection and 49 biopsy) were included. No significant differences were observed between groups regarding demographics, comorbidities, tumor characteristics, or International Extranodal Lymphoma Study Group scores. Preoperative midline shifting (p = 0.048) and steroid use (p < 0.001) were higher in the resection group, which also demonstrated greater symptom improvement (p < 0.001). The complication rates were comparable between groups. The 5-year overall survival (OS) was 81.3% (resection) vs. 80.1% (biopsy), and the 5-year progression-free survival (PFS) was 53.6% (resection) vs. 60.3% (biopsy), with no significant differences in OS or PFS by Cox regression analysis. Conclusions: Surgical resection does not improve OS or PFS in solitary, resectable PCNSL, though it may provide symptomatic relief in select cases. Further prospective studies are needed to define its role in PCNSL management.

To examine the correlation of apparent diffusion coefficient (ADC), diffusion weighted imaging (DWI), and T1 contrast enhanced (T1-CE) with Ki-67 in primary central nervous system lymphomas (PCNSL). And to assess the diagnostic performance of MRI radiomics-based machine-learning algorithms in differentiating the high proliferation and low proliferation groups of PCNSL.

83 patients with PCNSL were included in this retrospective study. ADC, DWI and T1-CE sequences were collected and their correlation with Ki-67 was examined using Spearman's correlation analysis. The Kaplan-Meier method and log-rank test were used to compare the survival rates of the high proliferation and low proliferation groups. The radiomics features were extracted respectively, and the features were screened by machine learning algorithm and statistical method. Radiomics models of seven different sequence permutations were constructed. The area under the receiver operating characteristic curve (ROC AUC) was used to evaluate the predictive performance of all models. DeLong test was utilized to compare the differences of models.

Relative mean apparent diffusion coefficient (rADCmean) (ρ=-0.354, p = 0.019), relative mean diffusion weighted imaging (rDWImean) (b = 1000) (ρ = 0.273, p = 0.013) and relative mean T1 contrast enhancement (rT1-CEmean) (ρ = 0.385, p = 0.001) was significantly correlated with Ki-67. Interobserver agreements between the two radiologists were almost perfect for all parameters (rADCmean ICC = 0.978, 95%CI 0.966-0.986; rDWImean (b = 1000) ICC = 0.931, 95% CI 0.895-0.955; rT1-CEmean ICC = 0.969, 95% CI 0.953-0.980). The differences in PFS (p = 0.016) and OS (p = 0.014) between the low and high proliferation groups were statistically significant. The best prediction model in our study used a combination of ADC, DWI, and T1-CE achieving the highest AUC of 0.869, while the second ranked model used ADC and DWI, achieving an AUC of 0.828.

rDWImean, rADCmean and rT1-CEmean were correlated with Ki-67. The radiomics model based on MRI sequences combined is promising to distinguish low proliferation PCNSL from high proliferation PCNSL.

Current prognostic scoring systems for newly diagnosed primary central nervous system lymphoma (PCNSL), such as IELSG prognostic score and MSKCC prognostic score, are widely used but have limitations in clinical practice. This study aimed to develop a novel prognostic model based on real clinical data and compare it with existing systems.

A total of 288 patients newly diagnosed with PCNSL were recruited. Patients were randomly allocated to the development and validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were used to identify the risk factors for overall survival (OS) and construct a nomogram. Additionally, Kaplan-Meier survival curves were plotted to show the stratification ability of the risk groups.

Eastern Cooperative Oncology Group performance status (ECOG-PS), albumin, and two inflammatory biomarkers D-Dimer, and neutrophil-to-lymphocyte ratio (NLR)-were independent predictors of inferior OS. The prognostic model demonstrated concordance Index (C-index) of 0.731 and 0.679 in the development and validation cohorts, respectively. In terms of the time dependent area under the curve (AUC) values for OS, the development cohort exhibited values of 0.765, 0.762, and 0.812 for 1-year, 3-year, and 5-year OS, respectively. The corresponding AUC values in the validation cohort were 0.711, 0.731, and 0.840, respectively. The calibration curves showed excellent concordance. The novel prognostic model also provided superior risk stratification for patients with PCNSL compared with existing scoring systems.

This study presents a novel prognostic model for predicting the OS of patients with newly diagnosed PCNSL. The model accurately and effectively stratifies the prognosis of patients with PCNSL and offers valuable clinical guidance for decision making.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma that is isolated in the central nervous system (CNS) or vitreoretinal space. High-dose methotrexate (HD-MTX)-based immunochemotherapy is the frontline for its treatment, with a high early response rate. However, relapsed or refractory (R/R) patients present numerous difficulties and challenges in clinical treatment. Chimeric antigen receptor (CAR)-T cells offer a promising option for the treatment of hematologic malignancies, especially in the R/R B-cell lymphoma and multiple myeloma. Despite the exclusion of most PCNSL cases from pivotal CAR-T cell trials due to their specific tumor microenvironment (TME), available preclinical and clinical studies with small cohorts suggest an overall acceptable safety profile and remarkable anti-tumor effects. In this review, we will provide the development process of CAR-T cells and summarize the research progress, limitations, and future perspectives of CAR-T cell therapy in patients with R/R PCNSL.

Currently, chimeric antigen receptor T-cell (CART) therapy represents a highly effective approach for relapsed/refractory B-cell lymphomas. However, it also carries treatment-related risks. Limited data are available on the risks associated with CART therapy in patients with gastrointestinal involvement in B-cell lymphomas. Therefore, we conducted a retrospective cohort study to address this gap in knowledge.

During the period from May 2019 to August 2022, a total of 26 patients recurrent/refractory with recurrent/refractory B-cell lymphoma involving the gastrointestinal tract enrolled. Pathology confirmed CD19 antigen expression in tumor tissues. The disease status of patients who failed multiple lines of therapy was progressive disease (PD). Before CART cell infusion, patients received an FC regimen (fludarabine and cyclophosphamide) lymphodepletion. Quantitative PCR and flow cytometry were adopted for monitoring CART cell kinetics and function, with a focus on gastrointestinal AEs during treatment. The overall response rate (ORR) of the 26 patients was 61.5% (16/26), while the complete response rate (CR) was 23.1% (6/26). Their median follow-up time was 22.49 months, while the medians of overall survival (OS) and progression-free survival (PFS) were 10.88 and 5.47 months, respectively. The 1-year OS and PFS rates were 45% and 42.3%, respectively. The prevalence of gastrointestinal complications was 21/26 (80.7%), including gastrointestinal hemorrhage in 11/26 (42.3%), emesis and diarrhea in 9/26 (34.6%), as well as intestinal obstruction in 2/26 (7.7%). A total of three patients (3/26, 11.5%) died of gastrointestinal hemorrhage. The gastrointestinal hemorrhage group exhibited markedly lower ORR and inferior OS compared to the non-hemorrhage group.

Generally, the CART cell therapy is valid in relapsed/refractory B-cell lymphoma with gastrointestinal involvement, but gastrointestinal bleeding is a unique risk factor that requires special attention, particularly in patients with high gastrointestinal tumor burden, as it is associated with poor efficacy and survival.

This study aims to investigate prognostic indicators and assess surgical interventions' impact on Primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNS-DLBCL) patients.

A comprehensive examination was performed on a group of 3,962 cases in the Surveillance, Epidemiology, and End Results (SEER) database, as well as 27 cases of PCNS-DLBCL from the First Affiliated Hospital of Wenzhou Medical University. The application of both univariate and multivariate Cox regression analyses facilitated the identification of significant risk factors associated with PCNS-DLBCL. Developing and verifying nomograms, the reliability of the nomogram was evaluated by C-index, ROC curve, calibration curve and decision curve analysis. Finally, by using Kaplan-Meier (KM) curves to assess the survival rates for PCNS-DLBCL patients.

Age, gender, marital status, tumor location, HIV infection status, chemotherapy, and surgical scopes emerged as independent prognostic factors for overall survival (OS) in multivariate Cox regression analysis, whereas gender did not demonstrate significance as a factor for cancer-specific survival (CSS). The C-index, calibration curves, ROC curves, and DCA curves demonstrating strong reliability and practicality. KM analysis revealed significantly improved OS and CSS in patients who underwent surgical resection compared to those who received no surgery/biopsy, especially receiving subtotal resection (STR). In addition, among patients receiving chemotherapy, both STR and gross total resection (GTR) improved survival time compared to chemotherapy alone, particularly with STR. In the non-chemotherapy group, GTR potentially improved CSS, there was no notable disparity in OS between patients who underwent surgery and those who did not or received biopsy.

This study analyzed prognostic factors in PCNS-DLBCL patients, resulting in nomograms predicting 1-, 3-, and 5-year OS and CSS, which showed preferable performance. Combining different resection scopes with chemotherapy improved survival compared to chemotherapy alone, advocating for integrated treatment strategies. Surgery alone is not recommended based on our findings.

In this retrospective unicentric study, we analyzed the medical records of 11 patients who were surgically treated for CNS lymphoma, both primary and secondary, between 2009 and 2024. Given the rarity of CNS lymphomas and their diverse signs and symptoms based on tumoral location, our aim was to describe key aspects, such as clinical presentations and surgical management. A possible relationship between obesity and CNS lymphoma progression was investigated through an analysis of previous study findings. The literature suggests a wide spectrum of manifestations, from nausea and headaches to loss of equilibrium and speech impairment. A predominance of unsystematized balance disorders and epileptic seizures were affirmed. Notably, as emerged from our study, aphasia was a particularly interesting neurological symptom due to its rarity in the clinical features of CNSL. Other significant factors, such as tumor localization and perioperative phases, were thoroughly investigated, with the latter highlighted by an illustrative case report. Additionally, a literature review was included, comprising nine recent retrospective studies on the efficacy of surgical resection for patients diagnosed with PCNSL.

Despite general acceptance that corticosteroid therapy (CST) should be withheld before biopsy for suspected primary central nervous system lymphoma (PCNSL), there remains conflicting evidence surrounding the precise impact of preoperative CST on the histopathological diagnosis. The objective of this systematic review and meta-analysis was to describe and quantify the effects of preoperative CST on the diagnostic accuracy of biopsies for PCNSL.

Primary articles were screened from Ovid MEDLINE, Embase, Web of Science, and Scopus databases. Meta-analysis was performed for immunocompetent patients with histologically confirmed PCNSL. Subgroup and regression analyses were performed to assess the effects of biopsy type, CST duration, dose, and preoperative taper on the diagnostic accuracy. In addition, the sensitivity of cerebrospinal fluid (CSF) analyses for PCNSL was assessed.

Nineteen studies, comprising 1226 patients (45% female; mean age: 60.3 years), were included. Preoperative CST increased the risk of nondiagnostic biopsy with a relative risk (RR) of 2.1 (95% CI: 1.1-4.1). In the stereotactic biopsy subgroup, the RR for nondiagnostic biopsy was 3.0 (95% CI: 1.2-7.5). CST taper, duration, and dose did not significantly influence diagnostic biopsy rates. The sensitivity of CSF cytology, including flow cytometry, for PCNSL was 8.0% (95% CI: 6.0%-10.7%).

Our results suggest that preoperative CST reduces the diagnostic yield of stereotactic biopsies for PCNSL. We found no evidence that tapering CST before biopsy improves diagnostic rates. CSF analysis currently has a poor sensitivity for the diagnosis of PCNSL.

Primary central nervous system lymphoma (PCNSL) is a rare but deadly malignancy that principally affects adults in the fifth and sixth decades of life. Despite diagnostic advances in analyses of cerebral spinal fluid and neuroimaging, definitive diagnosis of PCNSL requires primary brain tissue biopsy. While small neurosurgical biopsy volumes are pursued to minimize removal of normal brain tissue, the spatial margins to precisely biopsy pathologic tissue are narrow and can result in missed diagnoses. Furthermore, prior steroid treatment can significantly reduce tumor burden increasing the likelihood of a non-diagnostic biopsy.

A retrospective case report from a tertiary referral center using a combination of neuroradiological studies, sterotactic tissue biopsy, and molecular testing for genome mutations.

A 72-year-old woman with strong suspicion for PCNSL clinically and radiologically, but cerebral spinal fluid and primary brain tissue biopsy were negative for tumor. However, vitreous liquid biopsy molecular testing for a MYD88 mutation as well as B-cell clonality (IGH/IGK rearrangement) were positive, indicating the presence of secondary vitreoretinal lymphoma from PCNSL. Only after autopsy of her brain was histopathological and immunohistochemical evidence of PCNSL confirmed.

This case illustrates the unique contribution of liquid biopsy neuropathology-oriented molecular testing in a challenging case with high clinical suspicion of PCNSL in which gold-standard diagnostic testing failed to yield a diagnosis.

Aims/Background We aimed to investigate the impact of postoperative chemotherapy (POCT) on survival in patients with primary central nervous system lymphoma (PCNSL) using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods This study included 786 PCNSL patients, of which 605 received chemotherapy after surgery, and 181 did not. Data from the SEER registry database (2007-2020) were used to analyze PCNSL. Baseline information, including age, sex, race, marital status, primary tumour site, histological type, summary stage, surgical procedures, chemotherapy, and radiotherapy, was analyzed. Propensity Score Matching (PSM) (1:1) was employed to balance the effects of confounding variables between the two groups. Subsequently, Cox regression and bidirectional stepwise regression were used to identify independent prognostic factors. Kaplan-Meier (K-M) survival curves were constructed to assess the impact of POCT on patient prognosis. Additionally, two cases of PCNSL with typical magnetic resonance imaging appearances were presented. Results Multivariate Cox regression results revealed that age older than 60 years (hazard ratio [HR] = 1.786; 95% confidence interval [CI]: 1.272-2.509; p = 0.001) and absence of POCT (HR = 2.841; 95% CI: 2.159-3.738; p < 0.001) were independent prognostic risk factors, while primary tumour locations in the meninges (HR = 0.136; 95% CI: 0.032-0.569; p = 0.006) and other nervous system regions (HR = 0.552; 95% CI: 0.326-0.936; p = 0.027), as well as histological morphologies such as diffuse large B-cell lymphoma (HR = 0.233; 95% CI: 0.128-0.425; p < 0.001) and non-Hodgkin lymphoma (HR = 0.559; 95% CI: 0.356-0.876; p = 0.011), were associated with favourable patient outcomes. K-M curves demonstrated that the group undergoing POCT had a significantly more favourable prognosis compared to the non-POCT group, before (HR = 0.454; 95% CI: 0.343-0.600; p < 0.0001) or after PSM (HR = 0.580; 95% CI: 0.431-0.780; p < 0.0001). For patients with PCNSL, those with tumours located in the infratentorial region (HR = 0.231; 95% CI: 0.078-0.682; p = 0.046), supratentorial region (HR = 0.250; 95% CI: 0.163-0.383; p < 0.0001), overlapping brain regions (HR = 0.201; 95% CI: 0.056-0.727; p = 0.0058), and those who underwent biopsy (HR = 0.740; 95% CI: 0.463-1.182; p = 0.003), subtotal resection (STR) (HR = 0.490; 95% CI: 0.265-0.906; p = 0.0064), or gross total resection (GTR) (HR = 0.613; 95% CI: 0.292-1.287; p = 0.0003) had better prognoses in the postoperative chemotherapy group compared to the non-chemotherapy group. Conclusion POCT significantly improves the prognosis of PCNSL patients and identifies the characteristics of the benefiting population. This information aids clinical practitioners in designing personalized treatment plans for individuals and advancing precise treatment.

Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma, and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7 of 33 cases (21.2%) of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median, 3 vs 12 days; P = .027). This assay was then implemented in a Clinical Laboratory Improvement Amendments environment, with 2-day median turnaround for diagnosis of CNS lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation.

CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels.

Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features.

This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.

The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL.

We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery.

Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics.

Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.

Background: Treatment for refractory or relapsed primary CNS lymphoma (r/r PCNSL) is challenging. Salvage whole-brain radiation therapy (WBRT) is an option but has a short duration of disease control, so additional treatment modalities are warranted. Case: A 75-year-old female with r/r PCNSL who had multiple progressions after multiple lines of treatment underwent salvage WBRT. The patient received ibrutinib, a Bruton's tyrosine kinase inhibitor, as maintenance therapy for 18 months following WBRT with the intention of increasing survival duration after salvage WBRT. She survived 81 months from diagnosis, including 57 months after completion of WBRT. Conclusion: This case presentation describes the experience of using ibrutinib as maintenance therapy in treating r/r PCNSL after salvage WBRT.

Primary central nervous system lymphoma (PCNSL) presents a diagnostic enigma due to the inherent absence of lymphoid tissue in the central nervous system (CNS). The hypothesis posits that lymphocytes infiltrating the CNS during inflammatory responses could represent a cellular source for PCNSL, challenging traditional understandings of its etiology.

In 2 illustrative cases, patients presented with neurological symptoms initially misdiagnosed as encephalitis and demyelinating disease, respectively. These diagnoses were established based on clinical assessments and initial biopsy findings.

Subsequent biopsies, conducted months after the first signs of disease, confirmed the diagnosis of PCNSL in both patients. Identifying CD20-positive tumor cells was pivotal, indicating a B-cell lymphoma origin.

Treatment strategies included high-dose methotrexate chemotherapy for both patients. In addition, the second patient underwent adjuvant whole-brain radiotherapy after the chemotherapy regimen.

The therapeutic approach significantly reduced tumor size in both cases, with no evidence of recurrence observed during the follow-up period. This outcome underscores the potential efficacy of the chosen interventions.

In response to inflammatory lesions, lymphocyte infiltration into the CNS may serve as a pivotal origin for tumor cells in PCNSL. These cases highlight the complexity of diagnosing CNS disorders and suggest that various forms of encephalitis in the early stages could influence the prognosis of lymphoma. This insight into the cellular origins and treatment responses of PCNSL contributes to a broader understanding of its pathophysiology and management.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma with poor prognosis. 18F-flourodeoxyglucose positron emission tomography (PET)/magnetic resonance (MR) combines the advantages of PET and MR. The aim of this study is to evaluate the validity of PET/MR for the diagnosis of PCNSL by means of a meta-analysis.

Wanfang Database, SinoMed, China National Knowledge Infrastructure, the Cochrane Library, PubMed and Embase will be searched for candidate studies about PET/MRI in PCNSL diagnosis from database inception to October 2024. The following keywords will be applied: "Primary central nervous system lymphoma", "Primary intracerebral lymphoma", "Positron Emission Tomography Magnetic Resonance" and "PET-MR". Studies meeting the inclusion criteria will be included. Studies without full true positive, false positive, false negative and true negative values; studies reported in languages other than English and Chinese; conference abstracts not available in full text and case reports will be excluded. Quality Assessment of Diagnostic Accuracy Studies will be used to evaluate the study quality. The STATA software (V.15.0) and Meta-Disc software (V.1.4) will be used to carry out meta-analysis. When heterogeneity is evident, subgroup analysis will be used to investigate the origin of heterogeneity. The robustness of the analysis will be checked with sensitivity analysis.

This research is based on public databases and does not require ethical approval. The results will seek publication in a peer-reviewed journal after the completion of this systematic review and meta-analysis.

CRD42023472570.

Relapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the "real-world" use of relma-cel, especially for patients with CNS involvement.

Retrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events.

Among the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55-618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12-32 days).

This study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.

Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma.

A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed.

Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain.

This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.

Central nervous system (CNS) lymphomas, either primary or secondary in origin, are rare malignant tumors affecting the brain, spinal cord, or leptomeninges. Diagnosis of CNS lymphomas is complicated by their diverse clinical presentations, radiological features, and histopathological characteristics. Although frozen section (FS) analysis is commonly employed for various CNS tumors, its role and accuracy in CNS lymphoma diagnosis are less explored. In this study, we conducted a comparative analysis to assess the impact of knowledge of preoperative imaging on enhancing the accuracy of FS diagnosis in CNS lymphomas.

Data collection involved a retrospective review of CNS lymphoma patients from January 2009 to August 2021. Patients who underwent intraoperative consultation were included, excluding those with prior cortisone treatment. The dataset incorporated patient demographics, classification as primary or secondary lymphoma, radiological preliminary diagnoses, FS diagnosis, and permanent section diagnosis. We employed various archived materials, including FSs, touch imprint slides, crush cytology slides, H&E-stained sections, and immunohistochemical stains, and re-evaluated all slides for diagnostic validation.

Our study included 25 patients, of whom 60 % were female and had a mean age of 56.5 years. Preoperative radiology data were available for 80 % of cases, with preliminary diagnoses commonly including lymphoma and/or metastasis. Intraoperative consultation results indicated lymphoma in 18 (72 %) patients, with discordance observed in 28 % of cases when compared to permanent section diagnoses. Most permanent section diagnoses were diffuse large B-cell lymphomas (92 %), with the remainder being T-cell non-Hodgkin lymphoma (4 %) and follicular lymphoma (4 %). Intraoperative misdiagnoses were significantly associated with the absence of knowledge of preoperative imaging.

Our study demonstrates the reliability of FS diagnosis for CNS lymphomas during surgery, with a favorable complete concordance rate of 72 % when compared to permanent diagnoses. Importantly, lack of knowledge of preoperative imaging significantly impaired diagnostic accuracy in FS, emphasizing the need for close collaboration between pathologists and radiologists.

Talaromyces marneffei is prevalent in South Asia. Latent Talaromyces marneffei infection of travellers make the diagnosis difficult. There are similarities in clinical manifestations between Talaromyces marneffei infection and lymphoma. Brain abscess is a rare form of Talaromyces marneffei infection.

We reported a very rare case of a 19-year-old man with HIV infection who suffered from a brain mass and lymphadenopathy. His blood culture, bone marrow culture and sputum culture all grew Talaromyces marneffei. One month after treatment with voriconazole, the symptoms improved except brain mass. Surgical incision of the brain mass showed a compact mass, and pathological analysis showed the coexisting Talaromyces marneffei abscess and lymphoma. The patient is currently in a stable condition after receiving antifungal therapy and chemotherapy.

Based on a case report of a traveller who suffered from a brain mass of Talaromyces marneffei abscess and lymphoma after a visit to an endemic area, this review summarized the cases where there was confusion between lymphoma and the brain abscess of Talaromyces marneffei. Talaromyces marneffei infection can be found globally due to the increasing number of international travels. Talaromyces marneffei infection and lymphoma had similar characteristics which is easy to misdiagnose in clinic. Infection may also be accompanied by tumors, especially in patients infected with HIV. The manifestations and imaging of brain abscess of Talaromyces marneffei were not characteristic in different patients.

Diffuse large B-cell lymphoma (DLBCL) stands as a formidable challenge in the landscape of non-Hodgkin's lymphomas. This review illuminates the remarkable strides made in comprehending DLBCL's molecular intricacies and devising targeted treatments. DLBCL, the most prevalent non-Hodgkin's lymphoma, has seen transformative progress in its characterization. Genetic investigations, led by high-throughput sequencing, have unveiled recurrent mutations in genes such as MYC, BCL2, and BCL6, casting light on the underlying genetic chaos propelling DLBCL's aggressiveness. A pivotal facet of this understanding centers on cell signaling pathways. Dysregulation of B-cell receptor (BCR) signaling, NF-κB, PI3K/Akt/mTOR, JAK/STAT, Wnt/β-Catenin, and Toll-like receptor pathways plays a critical role in DLBCL pathogenesis, offering potential therapeutic targets. DLBCL's complex tumor microenvironment (TME) cannot be overlooked. The dynamic interplay among tumor cells, immune cells, stromal components, and the extracellular matrix profoundly influences DLBCL's course and response to therapies. Epigenetic modifications, including DNA methylation and histone changes, add another layer of intricacy. Aberrant epigenetic regulation plays a significant role in lymphomagenesis, offering prospects for epigenetic-based therapies. Promisingly, these molecular insights have spurred the development of personalized treatments. Targeted therapies and immunotherapies, guided by genomic profiling and molecular classification, are emerging as game-changers in DLBCL management. In conclusion, this review underscores the remarkable strides in understanding DLBCL's molecular underpinnings, spanning genetics, cell signaling, the tumor microenvironment, and epigenetics. These advances pave the way for more effective, personalized treatments, renewing hope for DLBCL patients.

Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for noninvasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy.

Multiple dMRI metrics including Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging, and Diffusion Microstructure Imaging were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology.

We found significantly increased intra-axonal volume fractions (V-intra and intracellular volume fraction) and microFA in PCNSL compared to GBM (all P < .001). In contrast, mean diffusivity (MD), axial diffusivity (aD), and microADC (all P < .001), and also free water fractions (V-CSF and V-ISO) were significantly lower in PCNSL (all P < .01). Receiver-operating characteristic analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF, and V-ISO (area under the curve [AUC] in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples.

Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.

Double expression lymphoma (DEL) is a subtype of primary central nervous system lymphoma (PCNSL) that often has a poor prognosis. Currently, there are limited noninvasive ways to detect protein expression.

To detect DEL in PCNSL using multiparametric MRI-based machine learning.

Retrospective.

Forty PCNSL patients were enrolled in the study among whom 17 were DEL (9 males and 8 females, 61.29 ± 14.14 years) and 23 were non-DEL (14 males and 9 females, 55.57 ± 14.16 years) with 59 lesions (28 DEL and 31 non-DEL).

ADC map derived from DWI (b = 0/1000 s/mm2 ), fast spin echo T2WI, T2FLAIR, and contrast-enhanced T1 weighted imaging (T1CE) were collected at 3.0 T.

Two raters manually segmented lesions by ITK-SNAP on ADC, T2WI, T2FLAIR and T1CE. A total of 2234 radiomics features from the tumor segmentation area were extracted. The t-test was conducted to filter the features, and elastic net regression algorithm combined with recursive feature elimination was used to calculate the essential features. Finally, 12 groups with combinations of different sequences were fitted to 6 classifiers, and the optimal models were selected.

Continuous variables were assessed by the t-test, while categorical variables were assessed by the non-parametric test. Interclass correlation coefficient tested variables' consistency. Sensitivity, specificity, accuracy F1-score, and area under the curve (AUC) were used to evaluate model performance.

DEL status could be identified to varying degrees with 72 models based on radiomics, and model performance could be improved by combining different sequences and classifiers. Both SVMlinear and logistic regression (LR) combined with four sequence group had similar largest AUCmean (0.92 ± 0.09 vs. 0.92 ± 0.05), and SVMlinear was considered as the optimal model in this study since the F1-score of SVMlinear (0.88) was higher than that of LR (0.83).

Multiparametric MRI-based machine learning is promising in DEL detection.

4 TECHNICAL EFFICACY STAGE: 2.

Primary central nervous system lymphoma(PCNSL) is an aggressive, rare form of Non-Hodgkin lymphoma, characterized by the absence of systemic disease. There are limited data and no strictly defined guidelines for management of PCNSL.

The aim of this study was to report a 10 year experience of PCNSL treatment, to evaluate treatment outcomes and asses Progression Free and Overall Survival of these patients.

Study was conducted on the Haematology Clinic, Clinical center University of Sarajevo, BH, in the period from January 2012.-December 2022. Total sample of 24 patients were enrolled. All have undergone diagnostic surgery. Patients were treated with regimens based on High dose Methotrexate, with/without whole brain radiotherapy as consolidation. Treatment response was captured by imaging techniques. Patients who have relapsed were evaluated with imaging techniques and treated according to Methotrexate-based treatment protocols.

We have captured equal gender distribution. The median age of patients was 59.5 years (range 20-79). Pathohistological analysis confirmed DLBCL diagnosis in 22 patients, T cell lymphoma and anaplastic large cell lymphoma, each in 1 patient. Chemotherapy, chemotherapy combined with WBRT and radiotherapy were given to 5, 18 and 1 patients, respectively. The overall complete response rate (CR) was 87,15%. Those receiving combined modality-treatment had higher CR than those receiving chemotherapy (94,4% versus 60%). Out of 24 patients, 11 of them relapsed. The median time to relapse was 29 months (from 1 to 105). After second line of the treatment, CR was 54,5%, while 45,45% of patients died during the treatment. 4 patients relapsed for the second time with median time to relapse of 9 months (from 2 to 77). 2 year OS rate was 67%, and the median OS rate was 45,9 months. 2 year PFS rate was 31%.

The OS and PFS rates indicate the usage of new drugs and consolidation with autologous stem cell transplantation in patients with PCNSL in order to achieve better treatment outcomes.

High-dose methotrexate (HD-MTX) combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL); however, some patients have adverse reactions.

To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.

Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HD-MTX until disease progression, intolerable toxicities, or physician/patient-directed withdrawal. Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria, respectively. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival, overall survival (OS), and safety.

The median follow-up duration was 14.7 mo (range, 3.9-30 mo). The ORR for all patients was 84.2%, and 2-year progression-free- and OS rates were 75.6% and 94.1%, respectively. All patients completed the induction phase, and nine patients underwent autologous stem cell transplantation as consolidation therapy, resulting in an ORR of 88.9%. Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%. All patients showed an acceptable safety profile. The sequencing results for cerebrospinal fluid (CSF) and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations. Circulating tumor DNA was correlated with disease relapse and response.

Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Purpose: To describe the long-term outcomes of 2 cases of primary autologous stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma-ophthalmic variant (PCNSL-O) or primary vitreoretinal lymphoma (PVRL). Methods: Two cases and their findings were analyzed. A review of the histopathology, systemic treatment, and multimodal ocular imaging was performed. Results: A 52-year-old woman and 56-year-old woman were referred for vitritis and retinal lesions suspicious for PCNSL-O. The initial vitreous biopsies were inconclusive. Both patients had subsequent chorioretinal biopsies that confirmed the diagnosis of diffuse large B-cell lymphoma. No systemic or central nervous system involvement was found on systemic workup. Both patients received intravitreal and systemic chemotherapy followed by ASCT, and both remained in complete remission 7 and 8 years later. Conclusions: These cases show the long-term survival of patients diagnosed with PVRL when primary ASCT, the primary treatment for PCNSL, is performed.

The present study aimed to determine whether combining diffusion-weighted (DWI) and dynamic susceptibility contrast-enhanced perfusion-weighted (DSC-PWI) magnetic resonance imaging (MRI) could differentiate between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). The present retrospective study evaluated 45 patients with histologically confirmed brain tumors, of which 18 had PCNSLs and 27 had GBMs. All patients underwent conventional, DWI, and DSC-PWI MRIs before the surgical removal of the lesion or stereotactic biopsy. The solid tumor component, peritumoral edema, and abnormal white matter were measured in three regions of interest to evaluate relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC) and DWI. In conventional MRI, there were significant differences in tumor numbers, tumor enhancement type, tumor necrosis, hemorrhage and open-ring sign between GBM and PCNSL. Solid tumor ADC and rCBV values (ADCt and rCBVt, respectively) and their ratios with abnormal white matter amounts were significantly higher in GBM cases than in PCNSL cases (P<0.05). The rCBV value for peritumoral edema (rCBVe) and its ratio with abnormal white matter amount (rCBVe/n) were significantly higher in GBM cases than in PCNSL cases (P<0.05). However, ADC values did not differ significantly for peritumoral edema. DWI values did not differ significantly. Combining rCBVt and rCBVe/n provided a perfect area under the receiver operating characteristic curve of 1.00, with 100% sensitivity and 100% specificity for distinguishing GBM from PCNSL. In the results of the present study, the major criterion in the decision-making process distinguishing PCNSL from GBM was the combined rCBVt and rCBVe/n parameter. A minor criterion was the ADCt value of the lesion.

Cerebral lymphoma is a rare and aggressive brain tumor. It accounts for 1% of all non-Hodgkin's lymphomas (NHL) and 2% of all brain tumors. Untreated brain lymphoma has a very poor prognosis, with an overall life expectancy of around 1.5 months.

The authors report the case of a 35-year-old patient, with no previous pathological history, who presented for 3 weeks with deafness and recently aggravated otalgia. In MRI, brain imaging revealed a formation initially suggestive of an aggressive meningioma, and the histological study of the operative specimen was in favor of a diffuse large-cell non-germ-center B NHL.

Primary central nervous system lymphoma is an extra-nodal NHL localized to the brain, meninges, spinal cord, and eyes. In 90% of cases, these are diffuse large B-cell lymphomas, the other types being poorly characterized low-grade lymphomas, T-cell lymphomas, and Burkitt's lymphomas. MRI with gadolinium contrast is the gold standard for diagnosis which enhancement is homogeneous and well-limited, frequently associated with perilesional vascular edema. In T2-weighted sequences, there is a weak signal with restricted diffusion on diffusion-weighted imaging. The management of brain lymphoma is currently based on chemotherapy with high-dose methotrexate combined with the other agents, mainly rituximab.

Cerebral lymphoma remains a non-negligible entity of central nervous system tumors, which can be confused with several other tumors, mainly glial and meningioma.

Diffuse large B-cell lymphoma (DLBCL) is the most common histopathological type of non-Hodgkin's lymphoma and might arise from various extranodal sites. Little is known about the clinical characteristics and survival outcomes of primary DLBCL of the brain, including the cerebrum, cerebellum, brain steam and ventricle (CCSV). Thus, we performed this study to explore the independent prognostic factors of CCSV-DLBCL using the Surveillance, Epidemiology, and End Results (SEER) database.

We extracted the data of patients diagnosed with CCSV-DLBCL between 1975 and 2016 from the SEER database. Variables including demographic characteristics, Ann Arbor stage and therapies, such as surgery, radiation and chemotherapy, were all collected. The prognostic factors on overall survival (OS) and disease-specific survival (DSS) were analysed using Kaplan-Meier curves.

One thousand three hundred and twenty-eight patients were finally enrolled in the analysis. The median age was 62 years old. More than half of the cases of CCSV-DLBCL (54.22%) originated from the cerebrum. Patients older than 75 years had the worst OS and DSS. Moreover, black people had the worst survival outcomes compared with white and other people. Surgery, radiation and chemotherapy all significantly improved OS and DSS.

To the best of our knowledge, this is the largest population-based study of CCSV-DLBCL. Advanced age, black race, lack of surgical resection, radiation or chemotherapy were all poor prognostic factors.

Primary central nervous system lymphoma (PCNSL) in pediatric patients presents diagnostic and treatment challenges, leading to delays and suboptimal strategies. Moreover, PCNSL in immunocompetent pediatric patients is rarely reported. This retrospective study aimed to describe the demographic and clinical features, as well as outcomes, of pediatric PCNSL cases.

A retrospective review was conducted on 11 immunocompetent pediatric patients diagnosed with PCNSL between January 2012 and April 2020. Data regarding age, gender, initial presenting symptoms, tumor location, and radiological characteristics were collected. Treatment strategies and analyzed prognosis were documented. Survival curves were generated using the Kaplan-Meir method, and data were analyzed using SPSS (version 23.0, IBM Corp.).

The study cohort comprised 11 patients, including 10 males and 1 female. The age at diagnosis ranged from 4 to 15 years, with a median age of 10.6 years. Headache was the most common presenting symptom, observed in 81.8% (9/11) of patients. Tumor locations in the supratentorial and infratentorial regions exhibited a similar occurrence rate. All tumors showed strong contrast enhancement on T1-weighted images. The average survival time for the 11 patients was 44.4 months. Among them, 5 patients died by the last follow-up visit, with a mean survival time of 8.8 months (one patient died in a car accident).

Headache is the predominant manifestation of PCNSL in pediatric patients. PCNSL demonstrates imaging characteristics resembling various intracranial tumors and is associated with a poor prognosis. Therefore, pediatric neurosurgeons should exercise caution in diagnosing and treating intracranial lymphoma.

The assessment of the cancer mutational profile is crucial for patient management, stratification, and therapeutic decisions. At present, in hematological malignancies with a solid mass, such as lymphomas, tumor genomic profiling is generally performed on the tissue biopsy, but the tumor may harbor genetic lesions that are unique to other anatomical compartments. The analysis of circulating tumor DNA (ctDNA) on the liquid biopsy is an emerging approach that allows genotyping and monitoring of the disease during therapy and follow-up. This review presents the different methods for ctDNA analysis and describes the application of liquid biopsy in different hematological malignancies. In diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), ctDNA analysis on the liquid biopsy recapitulates the mutational profile of the tissue biopsy and can identify mutations otherwise absent on the tissue biopsy. In addition, changes in the ctDNA amount after one or two courses of chemotherapy significantly predict patient outcomes. ctDNA analysis has also been tested in myeloid neoplasms with promising results. In addition to mutational analysis, liquid biopsy also carries potential future applications of ctDNA, including the analysis of ctDNA fragmentation and epigenetic patterns. On these grounds, several clinical trials aiming at incorporating ctDNA analysis for treatment tailoring are currently ongoing in hematological malignancies.

Primary central nervous system lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma that is confined within the CNS. Due to its ability to cross the blood-brain barrier, high-dose methotrexate (HDMTX) is the backbone for induction chemotherapy. This systematic review was conducted to observe outcomes among different HDMTX doses (low, <3 g/m²; intermediate, 3-4.9 g/m²; high, ≥5 g/m²) and regimens used in the treatment of PCNSL. A PubMed search resulted in 26 articles reporting clinical trials using HDMTX for PCNSL, from which 35 treatment cohorts were identified for analysis. The median dose of HDMTX used for induction was 3.5 g/m² (interquartile range IQR, 3-3.5); the intermediate dose was most frequently used in the studies examined (24 cohorts, 69%). Five cohorts used HDMTX monotherapy, 19 cohorts used HDMTX + polychemotherapy, and 11 cohorts used HDMTX + rituximab ± polychemotherapy. Pooled overall response rate (ORR) estimates for low, intermediate, and high dose HDMTX cohorts were 71%, 76%, and 76%, respectively. Pooled 2-year progression-free survival (PFS) estimates for low, intermediate, and high HDMTX dose cohorts were 50%, 51%, and 55%, respectively. Regimens that included rituximab showed a tendency to have higher ORR and 2-year PFS than those that did not include rituximab. These findings indicate that current protocols utilizing 3-4 g/m² of HDMTX in combination with rituximab provide therapeutic efficacy in PCNSL.

Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate the effect and tolerability of blood-brain barrier disruption treatment combined with high-dose treatment with autologous stem cell transplantation as consolidation on primary central nervous system lymphoma patients. We performed a prospective phase II study for 25 patients with previously untreated primary central nervous system lymphoma. The blood-brain barrier disruption treatment was initiated 3-4 weeks after the MATRix regimen using the previously optimized therapy protocol. Briefly, each chemotherapy cycle included two subsequent intra-arterial blood-brain barrier disruption treatments on days 1 and 2 via either one of the internal carotid arteries or vertebral arteries. Patients received the therapy in 3-week intervals. The treatment was continued for two more courses after achieving a maximal radiological response to the maximum of six courses. The complete treatment response was observed in 88.0% of the patients. At the median follow-up time of 30 months, median progression-free and overall survivals were not reached. The 2-year overall and progression-free survival rates were 67.1% and 70.3%, respectively. Blood-brain barrier disruption treatment is a promising option for primary central nervous system lymphoma with an acceptable toxicity profile.

Primary central nervous system lymphoma (PCNSL) is a rare form and aggressive type of diffuse large B-cell lymphoma (DLBCL) that occurs in both immunocompetent and immunocompromised adults. While adding rituximab to chemotherapeutic regimens resulted in dramatic improvement in both progression-free survival and overall survival in patients with non-central nervous system (CNS) DLBCL, the outcomes of PCNSL are generally poor due to the immune-privileged tumor microenvironment or suboptimal delivery of systemic agents into tumor tissues. Therefore, more effective therapy for PCNSL generally requires systemic therapy with sufficient CNS penetration, including high-dose intravenous methotrexate with rituximab or high-dose chemotherapy followed by autologous stem cell transplantation. However, overall survival is usually inferior in comparison to non-CNS lymphomas, and treatment options are limited for elderly patients or patients with relapsed/refractory disease. Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a cutting-edge cancer therapy, which led to recent FDA approvals for patients with B-cell malignancies and multiple myeloma. Although CAR-T cell therapy in patients with PCNSL demonstrated promising results without significant toxicities in some small cohorts, most cases of PCNSL are excluded from the pivotal CAR-T cell trials due to the concerns of neurotoxicity after CAR-T cell infusion. In this review, we will provide an overview of PCNSL and highlight current approaches, resistance mechanisms, and future perspectives of CAR-T cell therapy in patients with PCNSL.