OBJECTIVE: Primary central nervous system lymphoma (PCNSL) is a rare malignancy of the central nervous system with high invasiveness. There is little consensus on the treatment of PCNSL. This study retrospectively studied data from PCNSL patients in a single center to summarize treatment experience and explore prognostic factors.
METHODS: Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox\'s hazards model.
RESULTS: In multivariate analysis, cerebrospinal fluid lactic acid dehydrogenase (CSF LDH; p = 0.005 and p = 0.002), neutrophil to lymphocyte ratio (NLR; p = 0.014 and p = 0.038), and completion of four cycles of induction therapy (p < 0.001and p < 0.001) were significant and independent predictors of overall survival (OS) and progression-free survival (PFS), respectively.
CONCLUSIONS: On the basis of this study, we propose that PCNSL patients should receive early induction therapy with sufficient cycles. Subsequent consolidation therapy can prevent relapses and improve survival. In patients with PCNSL, the independent prognostic factors for OS and PFS were CSF LDH level, NLR, and full cycles of induction therapy.

Objective.Primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) are malignant primary brain tumors with different biological characteristics. Great differences exist between the treatment strategies of PCNSL and GBM. Thus, accurately distinguishing between PCNSL and GBM before surgery is very important for guiding neurosurgery. At present, the spinal fluid of patients is commonly extracted to find tumor markers for diagnosis. However, this method not only causes secondary injury to patients, but also easily delays treatment. Although diagnosis using radiology images is non-invasive, the morphological features and texture features of the two in magnetic resonance imaging (MRI) are quite similar, making distinction with human eyes and image diagnosis very difficult. In order to solve the problem of insufficient number of samples and sample imbalance, we used data augmentation and balanced sample sampling methods. Conventional Transformer networks use patch segmentation operations to divide images into small patches, but the lack of communication between patches leads to unbalanced data layers.Approach.To address this problem, we propose a balanced patch embedding approach that extracts high-level semantic information by reducing the feature dimensionality and maintaining the geometric variation invariance of the features. This approach balances the interactions between the information and improves the representativeness of the data. To further address the imbalance problem, the balanced patch partition method is proposed to increase the receptive field by sampling the four corners of the sliding window and introducing a linear encoding component without increasing the computational effort, and designed a new balanced loss function.Main results.Benefiting from the overall balance design, we conducted an experiment using Balanced Transformer and obtained an accuracy of 99.89%, sensitivity of 99.74%, specificity of 99.73% and AUC of 99.19%, which is far higher than the previous results (accuracy of 89.6% ∼ 96.8%, sensitivity of 74.3% ∼ 91.3%, specificity of 88.9% ∼ 96.02% and AUC of 87.8% ∼ 94.9%).Significance.This study can accurately distinguish PCNSL and GBM before surgery. Because GBM is a common type of malignant tumor, the 1% improvement in accuracy has saved many patients and reduced treatment times considerably. Thus, it can provide doctors with a good basis for auxiliary diagnosis.

Background: Due to the poor prognosis and rising occurrence, there is a crucial need to improve the diagnosis of Primary Central Nervous System Lymphoma (PCNSL), which is a rare type of non-Hodgkin\'s lymphoma. This study utilized targeted metabolomics of cerebrospinal fluid (CSF) to identify biomarker panels for the improved diagnosis or differential diagnosis of primary central nervous system lymphoma (PCNSL). Methods: In this study, a cohort of 68 individuals, including patients with primary central nervous system lymphoma (PCNSL), non-malignant disease controls, and patients with other brain tumors, was recruited. Their cerebrospinal fluid samples were analyzed using the Ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) technique for targeted metabolomics analysis. Multivariate statistical analysis and logistic regression modeling were employed to identify biomarkers for both diagnosis (Dx) and differential diagnosis (Diff) purposes. The Dx and Diff models were further validated using a separate cohort of 34 subjects through logistic regression modeling. Results: A targeted analysis of 45 metabolites was conducted using UHPLC-MS/MS on cerebrospinal fluid (CSF) samples from a cohort of 68 individuals, including PCNSL patients, non-malignant disease controls, and patients with other brain tumors. Five metabolic features were identified as biomarkers for PCNSL diagnosis, while nine metabolic features were found to be biomarkers for differential diagnosis. Logistic regression modeling was employed to validate the Dx and Diff models using an independent cohort of 34 subjects. The logistic model demonstrated excellent performance, with an AUC of 0.83 for PCNSL vs. non-malignant disease controls and 0.86 for PCNSL vs. other brain tumor patients. Conclusion: Our study has successfully developed two logistic regression models utilizing metabolic markers in cerebrospinal fluid (CSF) for the diagnosis and differential diagnosis of PCNSL. These models provide valuable insights and hold promise for the future development of a non-invasive and reliable diagnostic tool for PCNSL.

暂无摘要。

UNASSIGNED: Primary central nervous system lymphoma (PCNSL) is a type of extranodal non-Hodgkin lymphoma. Although there are widely used prognostic scores, their accuracy and practicality are insufficient. Thus, a novel prognostic prediction model was developed for risk stratification of PCNSL patients in our research.
UNASSIGNED: We retrospectively collected 122 patients with PCNSL from two medical centers in China from January 2010 to June 2022. Among them, 72 patients were used as the development cohort to construct a new model, and 50 patients were used for the validation. Then, by using univariate and multivariate Cox regression analsis and Lasso analysis, the Xijing model was developed and composed of four variables, including lesion number, β2-microglobulin (β2-MG), systemic inflammation response index (SIRI) and Karnofsky performance status (KPS). Finally, we evaluated the Xijing model through internal and external validation.
UNASSIGNED: Compared with the original prognostic scores, the Xijing model has an overall improvement in predicting the prognosis of PCNSL according to the time-dependent area under the curve (AUC), Harrell\'s concordance index (C-index), decision curve analysis (DCA), integrated discrimination improvement (IDI) and continuous net reclassification index (NRI). For overall survival (OS) and progression-free survival (PFS), the Xijing model can divide PCNSL patients into three groups, and shows more accurate stratification ability. In addition, the Xijing model can still stratify and predict prognosis similarly better in the elderly with PCNSL and subgroups received high-dose methotrexate (HD-MTX) or Bruton\'s tyrosine kinase inhibitors (BTKi). Finally, external validation confirmed the above results.
UNASSIGNED: Integrating four prognostic factors, including imaging findings, tumor burden, systemic inflammation response index, and comprehensive physical condition, we provided a novel prognostic model for PCNSL based on real-world data and evaluated its predictive capacity.

UNASSIGNED: High-dose methotrexate (HD-MTX)-based regimens are the standard treatment for patients with primary central nervous system lymphoma (PCNSL); however, MTX has extensive interpatient variability in pharmacokinetics and clinical outcomes, with genetic variation an important factor involved in the variability in drug response.
UNASSIGNED: 123 PCNSL patients who received 524 courses of chemotherapy were genotyped for 42 single nucleotide polymorphisms in MTX pathway. The relationship between these polymorphisms and the pharmacokinetics, clinical outcomes, and toxicity of MTX was explored using both univariate and multivariate analyses.
UNASSIGNED: We found ABCB1 rs2032582 and GGH rs2305558 were substantially associated with the pharmacokinetics of MTX. Patients with GGH rs2305558 T and ABCB1 rs2032582 non-G allele had a higher Cmax increased by 20.5%, area under the concentration-time curve (AUC0-48h) increased by 19.6% and lower clearance decreased by 19.6%. ABCB1 rs1045642 and rs2032582 might be independent predictors of progression-free survival. Patients with ABCB1 rs1045642 non-A and rs2032582 G allele correlated with higher progression risk of the disease. Furthermore, ATIC rs3821353 was associated with MTX-induced hepatotoxicity (Grade ≥ 2).
UNASSIGNED: These variants may serve as biomarkers to predict the pharmacokinetics, clinical outcomes, and hepatotoxicity of MTX and contribute to personalized therapy for PCNSL patients.

Primary central nervous system lymphoma (PCNSL) is a highly aggressive brain tumor with poor prognosis if no treatment. The activation of the NF-κB (nuclear factor kappa-B) is the oncogenic hallmark of PCNSL, and it was driven by B cell receptor (BCR) and Toll-like receptor (TLR) signaling pathways. The emergence of Bruton\'s tyrosine kinase inhibitors (BTKis) has brought the dawn of life to patients with PCNSL. This review summarizes the management of PCNSL with BTKis and potential molecular mechanisms of BTKi in the treatment of PCNSL. And the review will focus on the clinical applications of BTKi in the treatment of PCNSL including the efficacy and adverse events, the clinical trials currently being carried out, the underlying mechanisms of resistance to BTKi and possible solutions to drug resistance.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma with poor prognosis. In recent years, the emergence of genetic subtypes of systematic diffuse large B-cell lymphoma has highlighted the importance of molecular genetics, but large-scale research on the molecular genetics of PCNSL is lacking. Herein, we summarize the frequent gene mutations and discuss the possible pathogenesis of PCNSL. Myeloid differentiation primary response gene 88 (MYD88) and CD79B mutations, which cause abnormal activation of noncanonical nuclear factor-κB, are prominent genetic abnormalities in PCNSL. They are considered to play a major role in the pathogenesis of PCNSL. Other genes, such as caspase recruitment domain family member 11 (CARD11), tumor necrosis factor alpha induced protein 3 (TNFAIP3), transducin (β)-like 1 X-linked receptor 1, cyclin dependent kinase inhibitor 2A, PR domain zinc finger protein 1, and proviral insertion in murine malignancies 1, are also frequently mutated. Notably, the pathogenesis of immune insufficiency-associated PCNSL is related to Epstein-Barr virus infection, and its progression may be affected by different signaling pathways. The different mutational patterns in different studies highlight the heterogeneity of PCNSL. However, existing research on the molecular genetics of PCNSL is still limited, and further research into PCNSL is required to clarify the genetic characteristics of PCNSL.

UNASSIGNED: Primary central nervous system lymphoma (PCNSL) responds favorably to radiation, chemotherapy and targeted drug therapy. However survival is usually worse, the treatment-related drug resistance and recurrence are still clinical problems to be solved urgently. Studies have shown that cytokines are expressed in varying degrees in patients with lymphoma, which is significantly related to the progression, poor prognosis and drug resistance of lymphoma. We explore the expression and clinical significance of Th1/Th2/Th17 cytokines and lymphocyte subsets in patients with PCNSL to provide a more sufficient theoretical basis for its diagnosis and treatment.
UNASSIGNED: We measured and analysed the levels of Th1/Th2/Th17 cytokines and the distribution of lymphocyte subsets (including Treg cells, CD3+, CD4+, CD8+, CD19+, and CD4+/CD8+) in 39 patients with PCNSL and 96 patients with diffuse large B-cell lymphoma (DLBCL) without central nervous system involvement. The cytokines of 13 healthy people and the lymphocyte subsets of 27 healthy people were measured as the control group.
UNASSIGNED: We found a significant difference in the level of Th1/Th2/Th17 cytokines and lymphocyte subsets between PCNSL and healthy controls, especially IL-2, after treatment, which was significantly higher than before treatment (p<0.01). However, the level of CD19+ and CD4+/CD8+ decreased while CD8+ and CD3+ increased after treatment (regardless of whether the treatment was effective), and the difference was statistically significant. In addition, our analysis of different prognostic factors found that HD-MTX-based chemotherapy appears to have a longer progression-free survival and overall survival than osimertinib-based chemotherapy.
UNASSIGNED: There are significant differences in Th1/Th2/Th17 cytokines and lymphocyte subsets among PCNSL, DLBCL, and healthy controls, and their detection is helpful for the diagnosis, treatment, and prognosis of PCNSL. HD-MTX-based chemotherapy may still be the first choice for PCNSL.

UNASSIGNED: To analyse the clinical characteristics and therapeutic response of Chinese patients with primary extranodal diffuse large B-cell lymphoma DLBCL (PE-DLBCL).
UNASSIGNED: We analysed the clinical features and outcomes of 197 patients who were newly diagnosed with PE-DLBCL between January 2015 and December 2020.
UNASSIGNED: The gastrointestinal tract showed the highest rate of involvement (34%), followed by the central nervous system (CNS) and intraocular system (31.5%). The 3-year overall survival (OS) rate was 81% for the entire group and 79% for those with CNS and vitreoretinal involvement. Ann Arbour stage, lactate dehydrogenase level, International Prognostic Index > 2, and complete remission (CR) were significantly related to the survival of patients with PE-DLBCL. The lack of CR was the only independent adverse prognostic factor for OS.
UNASSIGNED: The clinical outcomes of patients with PE-DLBCL at our centre were encouraging, especially for patients with CNS and vitreoretinal involvement.