Central Nervous System Lymphoma Research Articles

Sarcopenia is a prognostic factor in lymphoma patients: a systematic review and meta-analysis

Findings regarding the relationship between sarcopenia and lymphoma have been inconsistent across studies. This study investigated the association between sarcopenia and lymphoma. We systematically searched the Embase, Science Direct, Cochrane Library, and PubMed databases from inception to 31 March 2024 to identify relevant studies. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Twenty-six studies with 3659 participants were included. Sarcopenic lymphoma patients had poor overall survival (OS) (HR = 1.88; 95% CI: 1.47–2.41; p < 0.001). The heterogeneity was high (I2=80%). However, the result of the Egger test indicated a significant publication bias (p < 0.001). After employing the trim and fill method to adjust for this bias, the HR of OS became non-significant (p > 0.05). The progression-free survival (PFS) was worse in sarcopenic patients (HR = 1.77; 95% CI: 1.37–2.29; p < 0.001; I2=70%). There was no significant publication bias (p > 0.05). In the subgroup analyses, sarcopenia was a negative predictor of OS in lymphoma patients who undergo hematopoietic cell transplantation (HCT) (HR = 1.61;95% CI: 1.19–2.18; I2=30%). Male lymphoma patients with sarcopenia had a significantly worse OS (HR = 2.29; 95% CI:1.24–4.24; p = 0.009). Among patients with primary central nervous system lymphoma (PCNSL), those with sarcopenia defined by temporal muscle thickness (TMT) exhibited significantly worse OS (HR = 2.20; 95% CI:1.04–4.65; p = 0.039; I2=68%). Sarcopenia is associated with worse PFS in lymphoma patients. Subgroup analyses indicate that sarcopenia is a negative predictor of OS after HCT, and male lymphoma patients who suffer from sarcopenia have higher mortality. Sarcopenia defined by TMT is also a negative predictor of OS for patients with PCNSL.

Lymphomatosis cerebri caused by adult T cell leukemia/lymphoma: a differential diagnosis for depression: a case report

BackgroundPrimary central nervous system lymphoma is rare, and primary central nervous system T cell lymphoma is relatively uncommon, contributing to < 5% of all cases. Lymphomatosis cerebri, a rare subtype of primary central nervous system lymphoma, is characterized by extensive white-matter lesions on magnetic resonance imaging and nonspecific symptoms, such as cognitive decline and depression. Reports of lymphomatosis cerebri in adult T cell leukemia/lymphoma are limited.Case presentationA 49-year-old Japanese man gradually developed insomnia, anorexia, and weight loss over a 2-month period following work-related promotion. Initially diagnosed with depression, his condition rapidly deteriorated with cognitive decline and motor dysfunction. Despite various treatments, his symptoms persisted within a month. Upon admission, the presence of neurological abnormalities suggestive of a central nervous system disorder raised suspicion of a cerebral lesion. Diagnostic tests revealed extensive brain lesions on imaging and the presence of atypical lymphocytes (flower cells) in the cerebrospinal fluid. The patient was diagnosed with lymphomatosis cerebri due to adult T cell leukemia/lymphoma, a rare presentation in the literature. Due to irreversible brainstem damage and poor neurological prognosis, aggressive treatment was not initiated, and the patient died, with an autopsy confirming the diagnosis.ConclusionLymphomatosis cerebri with adult T cell leukemia/lymphoma is very rare. It is crucial to promptly consider lymphomatosis cerebri as a differential diagnosis, particularly in cases of rapid cognitive decline and poor treatment response. Recognition of lymphomatosis cerebri as an important differential diagnosis for cognitive decline, and depression is necessary for timely intervention and management. Further research is required to better understand this unique and rare presentation in adult T cell leukemia/lymphoma.

Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

The Prognostic Significance of Pontine-White Matter Score in Primary Central Nervous System Lymphoma Patients.

Limited data exist on the significance of PET imaging and quantitative PET parameters in primary central nervous system (CNS) lymphoma due to its relative rarity. This study was conducted to investigate the prognostic value of a novel internal standardization indicator, the pontine-white matter (PW) score, in primary CNS lymphoma patients undergoing post-treatment 18F-FDG PET/CT and PET/MR imaging. From January 2014 to December 2022, eligible patients with primary CNS lymphoma who underwent post-treatment PET imaging were enrolled. Using the FDG uptake of the pons and white matter as an internal reference, the PW score was graded based on the metabolism of the post-therapeutic lesion for each patient, and its associations with patients' prognosis were investigated. In total, 41 patients with post-treatment PET/CT and 49 patients with post-treatment PET/MR imaging were enrolled. ROC curve analysis indicated that the PW score possessed robust discriminative ability in distinguishing patients with worse outcomes. Furthermore, a higher PW score was significantly correlated with and identified as an independent prognostic indicator for, worse prognosis in both the PET/CT and PET/MR cohorts. The study demonstrated that the PW score was an effective prognostic indicator for identifying post-treatment primary CNS lymphoma patients with worse outcomes.

Histopathological and medico-legal aspects in a case of death related to an undiagnosed cerebral large B-cell lymphoma.

We report an unusual and undetected case of primary central nervous system lymphoma presenting as multiple lesions in the periventricular occipital lobe in an immunocompetent host, which had manifested as a stroke. The neoplastic diagnosis was made only after death following a thorough autopsy and histopathological examinations which enabled the diagnosis of a rare cancer (primary cerebral lymphoma) which remained undetected and undiagnosed during life.

Vitreoretinal large B- cell lymphoma (VR- LBCL): Clinical and pathological features and treatment outcomes

ContextVitreoretinal large B- cell lymphoma (VR- LBCL) is a type of non- Hodgkin lymphoma confined to the eye and central nervous system (CNS). The clinical manifestations of intraocular lymphoma can precede, occur simultaneously with, or follow disease at CNS sites. It differs from other forms of extra-nodal lymphoma; in that it does not involve systemic sites other than CNS. ObjectivesTo analyse the clinical and pathological features, and treatment outcomes of a cohort of patients diagnosed with vitreoretinal lymphoma (VRL) in Royal Victoria Eye and Ear Hospital, Ireland between 2010 and 2024. MethodRetrospective review of medical records and pathology specimens of patients with ocular involvement in VR- LBCL over 14-year period and a review of the literature. ResultsEight patients were included. All of them underwent pars plana vitrectomy and were confirmed to have VR- LBCL. The median age at diagnosis was 71 years. Three were men and five were women. Six had bilateral disease and two unilateral. Four of four patients had MYD88 L265P mutation present. Four patients showed a high interleukin-10 (IL-10) to interleukins-6 (IL-6) ratio in keeping with the diagnosis of VRL. Three patients had primary CNS lymphoma with subsequent eye involvement, despite systemic chemotherapy treatment. Of the five patients who presented with ocular lymphoma, two patients had CNS involvement after primary vitreoretinal lymphoma was diagnosed. Of those, one was initially treated with local intravitreal chemotherapy. Three patients had no CNS recurrence. At the time of this study, seven patients of eight are alive, four are disease free and two are on a first- line local chemotherapy treatment. One underwent treatment for CNS relapse. One patient died of the disease before commencing targeted therapy. ConclusionThis case series demonstrated excellent treatment outcomes for seven patients, alive at the time of the study. Both local radiotherapy and intravitreal chemotherapy achieved good ocular control with acceptable side effects and no significant difference in visual outcome. VRL is a difficult diagnosis and vitreous cytology should be prioritised in cases of vitritis unresponsive to treatment. Analysis of MYD88 L265P mutation and IL- 10: IL- 6 ratio >1 are useful adjuncts in the diagnosis of VR- LBCL, particularly in cases where limited vitreous material makes cytological evaluation challenging.

Indications for a brain biopsy in neurological diseases of unknown etiology: The role of magnetic resonance imaging findings and liquid biopsy in yielding definitive pathological diagnoses

Brain biopsies are often considered for patients who cannot be diagnosed with various laboratory test results. However, physicians tend to be hesitant regarding their application in possibly non-neoplastic brain diseases, due to the invasiveness and risks. The aim was to determine the indications for brain biopsies in cases of neurological diseases of unknown etiology. We retrospectively evaluated diagnostic accuracy, laboratory findings (including a liquid biopsy for malignant lymphoma), magnetic resonance imaging (MRI) characteristics and the post-treatment outcomes of patients undergoing brain biopsies for neurological diseases of unknown etiology. The data of patients who had undergone a brain biopsy during their admission to Niigata University Hospital, between 2011 and 2024, were reviewed. Moreover, the laboratory data and MRI findings between patients with definitive and nonspecific biopsy diagnoses were compared. Twenty-six patients underwent a brain biopsy, and a definitive diagnosis was obtained in 14 patients (53.8%). Even in cases where a nonspecific diagnosis was made, biopsy findings helped rule out malignancy and guide clinical diagnosis and treatment decisions. The liquid biopsy for malignant lymphoma was performed in eight patients, with one yielding a positive result, consistent with primary central nervous system lymphoma. The sensitivity and specificity of liquid biopsy were 0.5 and 1, respectively. Diffusely contrasted cortical lesions and the presence of mass effects on MRI, were significantly associated with a definitive diagnosis, compared to a nonspecific diagnosis. In conclusion, brain MRI and liquid biopsies can assist in determining the appropriate indications for brain biopsies in neurological diseases of unknown etiology.

The Use of Stem Cell Therapy in the Treatment of Primary Central Nervous System Lymphoma

The Use of Stem Cell Therapy in the Treatment of Primary Central Nervous System Lymphoma

Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights.

To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication. In this case-control study, we validated 17 cytokines/chemokines (interleukin [IL]-1-beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, interferon-gamma, and tumor necrosis factor [TNF]-alpha) in a multiplexed automated immunoassay system (ELLA; Bio-Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011-02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin-4 immunoglobulin G positivity, non-inflammatory disorders, and healthy individuals were used as controls. A total of 32 NS patients (59% women; median age, 59 years [19-81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin-4 immunoglobulin G positive, and 34 patients with non-inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL-2, IL-6, IL-10, IL-13, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, interferon-gamma, and TNF-alpha levels were significantly higher in NS patients compared with non-inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL-6, CXCL9, CXCL10, GM-CSF, interferon-gamma, and TNF-alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL-6, IL-10, IL-13, CXCL9, CXL10, GM-CSF, and TNF-alpha associated with measures of disease activity. NS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B-cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024.

The Silent Masquerade: Clinical and Imaging Features of Asymptomatic Vitreoretinal Lymphoma

PurposeTo report and characterize ocular features of asymptomatic vitreoretinal lymphoma (VRL) associated with primary central nervous system lymphoma (PCNSL), by examining clinical and multimodal imaging characteristics and comparing with symptomatic VRL. DesignRetrospective cross-sectional study. MethodsPatients with cytologically or molecularly confirmed VRL were included. Patients were classified into three groups: primary VRL (PVRL), symptomatic VRL associated with PCNSL (PCNSL-S), or asymptomatic VRL associated with PCNSL (PCNSL-AS). Data encompassing demographics, visual symptoms, visual acuity (VA), and imaging characteristics were collected. Cross-sectional analyses of quantitative and categorical variables among groups were performed with one-way ANOVA and multinomial linear regression analyses. ResultsThe study included 104 eyes from 56 patients with VRL. Twenty-nine patients (52%) were diagnosed with PVRL, and 27 patients (48%) were diagnosed with VRL associated with PCNSL. Among these, 17 (63%) reported visual symptoms (PCNSL-S), whereas 10 (37%) were asymptomatic (PCNSL-AS). PCNSL-AS patients exhibited better VA than PVRL patients (0.11 vs. 0.76 LogMAR, p=0.04) and distinct clinical features, with lower rates of anterior segment involvement (odds ratio [OR]=0.02; 95% confidence interval [CI] 0.12-0.84; p<0.01) and vitritis (OR= 0.32; 95%CI 0.11-0.91; p=0.03). Subretinal infiltration was less common in PCNSL-AS cases compared to PVRL (OR= 0.14; 95%CI 0.02-1.11; p=0.06) and PCNSL-S (OR: 0.08; 95%CI 0.01-0.69 p=0.05) and was associated with worse VA (estimate=0.55 LogMAR; 95%CI 0.29-0.8; p<0.01). ConclusionThis study describes distinctive clinical and imaging features of asymptomatic VRL associated with PCNSL, characterized by better VA and less severe ocular involvement. The findings highlight the pivotal role of multimodal imaging in facilitating early detection of VRL in the staging of PCNSL. Future guidelines for PCNSL management should consider the necessity of diagnosing patients with asymptomatic VRL.

Prognostic Assessmentin Patients With Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System Using MRI-Based Radiomics.

Primary central nervous system lymphoma (PCNSL) carries a poor prognosis. Radiomics may hold potential value in prognostic assessment. To develop and validate an MRI-based radiomics model and combine it with clinical factors to assess progression-free survival (PFS) and overall survival (OS) of patients with PCNSL. Retrospective and prospective. Three hundred seventy-nine patients (179 female, 53 ± 7 years) from 2014 to 2022. T2/fluid-attenuated inversion recovery, contrast-enhanced T1WI and diffusion-weighted echo-planar imaging sequences on 3.0 T. Radiomics features were extracted from enhanced tumor regions on preoperative multi-sequence MRI. Using a least absolute shrinkage and selection operator (LASSO) Cox regression model to select radiomic signatures in training cohort (N = 169). Cox proportional hazards models were constructed for clinical, radiomics, and combined models, with internal (N = 72) and external (N = 32) cohorts validating model performance. Chi-squared, Mann-Whitney, Kaplan-Meier, log-rank, LASSO, Cox, decision curve analysis, time-dependent Receiver Operating Characteristic, area under the curve (AUC), and likelihood ratio test. P-value <0.05 was considered significant. Follow-up duration was 28.79 ± 22.59 months (median: 25). High-risk patients, determined by the median radiomics score, showed significantly lower survival rates than low-risk patients. Compared with NCCN-IPI, conventional imaging and clinical models, the combined model achieved the highest C-index for both PFS (0.660 internal, 0.802 external) and OS (0.733 internal, 0.781 external) in validation. Net benefit was greater with radiomics than with clinical alone. The combined model exhibited performance with AUCs of 0.680, 0.752, and 0.830 for predicting 1-year, 3-year, and 5-year PFS, and 0.770, 0.789, and 0.863 for OS in internal validation, with PFS AUCs of 0.860 and 0.826 and OS AUCs of 0.859 and 0.748 for 1-year and 3-year survival in external validation. Incorporating a multi-sequence MR-based radiomics model into clinical models enhances the assess accuracy for the prognosis of PCNSL. 4 TECHNICAL EFFICACY: Stage 2.

MRI-based radiomics signatures for preoperative prediction of Ki-67 index in primary central nervous system lymphoma

PurposeThe aim of this study was to develop and validate radiomics signatures based on MRI for preoperative prediction of Ki-67 proliferative index (PI) expression in primary central nervous system lymphoma (PCNSL). MethodsA total of 341 patients with PCNSL were retrospectively analyzed, including 286 patients in one center as the training set and 55 patients in another two centers as the external validation set. Radiomics features were extracted and selected from preoperative contrast-enhanced T1-weighted images, fluid attenuation inversion recovery to build radiomics signatures according to the Ki-67 PI. The predictive performances of the radiomics model were evaluated using four classifiers including random forest, K-Nearest Neighbors, Neural Network and Decision Tree. A combined model was built by incorporating radiomics signature, clinical variables and MRI radiological characteristics using multivariate logistic regression analysis, and a nomogram was established to predict the expression of Ki-67 individually. The predictive performances of the models were evaluated using area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). ResultsRadiomics signatures were independent predictors of the expression level of Ki-67 (OR: 2.523, P < 0.001). RF radiomics models had the highest accuracy (0.934 in the training set and 0.811 in the external validation set) and F1 Score (0.920 in the training set and 0.836 in the external validation set). The clinic-radiologic-radiomics nomogram showed better predictive performance with AUCs of 0.877(95 % CI: 0.837–0.918) in the training set and 0.866(95 % CI: 0.774–0.957) in the external validation set. The calibration curve and DCA demonstrated goodness-of-fit and improved benefits in clinical practice of the nomogram. ConclusionsNomograms integrating MRI-based radiomics and clinical-radiological characteristics could effectively predict Ki-67 PI in primary PCNSL.

Association of focus score and extraglandular involvement in Sjögren's syndrome: A study on antinuclear antibodies and minor salivary gland pathology

Objectives: This study aimed to investigate the relationship between patients with and without extraglandular involvement in Sjögren's syndrome (SS) by analyzing ANA (antinuclear antibody) and ENA (extractable nuclear antigen) results and minor salivary gland pathology findings. Patients and methods: A total of 265 (245 females; 20 males; mean age: 50.4±12.4; range, 19 to 79 years) patients diagnosed with SS were included in the retrospective cohort study between March 1, 2011, and December 1, 2021. Detailed documentation was performed, capturing demographic characteristics, clinical information, laboratory findings, medication usage, and manifestations of the syndrome. The patients were divided into two groups, with (78 females; 8 males; mean age: 52.7±11.5; range, 22 to 78 years or without (167 females; 12 males; mean age: 49.3±12.8; range, 19 to 79 years extraglandular involvement. Results: The mean follow-up duration was 63.1±31.9 months. Extraganular involvement, including joint involvement, lung involvement, central nervous system involvement, hematological involvement, hepatitis, and lymphoma, was observed in 32.5% of the patients. Patients with extraglandular involvement required multiple medications, while those with only glandular involvement predominantly used hydroxychloroquine. The mean duration from SS diagnosis to extraglandular involvement was 15.2±27.8 months. The comparison between patients with and without extraglandular involvement revealed a significant association between higher focus scores (FS) and extraglandular manifestations. However, no significant differences were observed in terms of ANA positivity, ANA titers, or ENA positivity. Regression analysis indicated that age and FS were linked to systemic involvement. Conclusion: This study highlights the importance of FS as a predictive indicator for extraglandular manifestations in SS. Advanced age was found to be associated with an increased likelihood of extraglandular involvement. Assessing FS and age can aid in predicting extraglandular manifestations.

Neurolymphomatosis secondary to primary central nervous system lymphoma: illustrative case.

Neurolymphomatosis (NL) is a rare disease defined as an invasion of lymphoma into peripheral nerves, nerve roots, or nerve plexuses, including the cranial nerves. No clear treatment protocols have yet been defined for this pathology. A woman in her 40s had a primary central nervous system lymphoma diagnosed from an intracranial tumor biopsy and underwent chemotherapy and radiation therapy. After she complained of pain in the trunk and extremities, magnetic resonance imaging and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) performed 25 months after initial diagnosis revealed multiple lesions in the nerve ganglia, plexuses, and peripheral nerves from the cervical to the sacral spinal cord. Cerebrospinal fluid cytology revealed atypical lymphocytes and lymphoma dissemination in the spinal cavity. Based on these findings, NL was diagnosed. An intrathecal antineoplastic regimen temporarily reduced abnormal uptake of FDG, but the lesion recurred. After additional high-dose methotrexate therapy, FDG accumulation in the previously identified lesions disappeared. However, peripheral neuropathic pain and paraplegia remained. The patient died 9 months after the initial diagnosis of NL. The authors reported a case of NL following primary central nervous system lymphoma. In this case, FDG-PET proved useful for diagnosis, and high-dose methotrexate therapy was temporarily effective. https://thejns.org/doi/suppl/10.3171/CASE24107.

Primary Leptomeningeal Lymphoma in HIV-infected Patients Presented with Subacute Meningitis

Primary leptomeningeal lymphoma (PLML) is extremely rare, accounting for only 7% of all primary central nervous system lymphomas. We present a case of PLML in a person living with HIV with controlled disease, presented with low cerebrospinal fluid sugar meningitis and leptomeningeal nodular enhancement, posing a diagnostic difficulty because the presentation resembled infectious diseases.

Prognostic Value of CSF IL-10 at Early Assessment of Induction Chemotherapy in Primary CNS Lymphomas: A LOC Network Study.

Despite a high response rate at the first evaluation during induction chemotherapy, the risk of early relapse remains high and unpredictable in primary CNS lymphomas (PCSNLs). We aimed to assess the prognostic value of early IL-10 levels in CSF (e-IL-10) after 2 months of induction chemotherapy. We retrospectively selected from the LOC (Lymphomes Oculo-Cérébraux) network database patients with PCSNLs who had complete or partial response at the 2-month evaluation of a high-dose methotrexate-based first-line chemotherapy for whom e-IL-10 was available. Thirty patients (median age: 62 years, brain involvement in 30/30, CSF involvement in 10/30, median baseline CSF IL-10: 27.5 pg/mL) met the selection criteria. e-IL-10 was undetectable in 22 patients and detectable in 8 patients. At the end of induction treatment, 7 of 8 and 4 of 22 of the patients with detectable and undetectable e-IL-10 had experienced progressive disease, respectively (p = 0.001, OR: 26.8, 95% CI 2-1,478). The median progression-free survival times were 5.8 months (95% CI 2.8-8.8) and 28.7 months (95% CI 13.4-43.9) in the groups with detectable and undetectable e-IL-10, respectively (p < 0.001). Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.

Outcomes and Relapse Patterns in Primary Central Nervous System Lymphoma: Longitudinal Analysis of 559 Patients Diagnosed From 1983-2020.

Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow up. T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983-2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, other. Progression-free (PFS) and overall (OS) survival was assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse. Median follow-up was 7.4 years (N=559). Most (321, 57%) were recursive partitioning analysis class 2 (age≥50, KPS≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs. PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5-years for 351 patients with CR/CRu to consolidation was 80% (95%CI:76-84%) and 46% (95%CI:41-53%), respectively; 1-year cumulative incidence of local vs non-local relapse was 1.8% vs 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local vs non-local relapse was 57% vs 42%, respectively. Deep structure involvement (HR 1.89, 95%CI:1.10-3.27) was associated with local relapse in refractory patients. We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.

Imaging Features of Immunodeficiency-Associated Primary CNS Lymphoma: A Review.

In the immunocompromised setting, there are distinct radiologic findings of primary central nervous system lymphoma (PCNSL), including necrotic ring-enhancing lesions, increased propensity for intralesional haemorrhage, and multiplicity. In this clinical context, advanced imaging with MR perfusion, spectroscopy, and diffusion-weighted imaging can be used to increase accuracy in the diagnosis of lymphoma over mimics such as high-grade glioma, metastases, or infection. This review summarizes the histology and pathophysiology of PCNSL in immunodeficient hosts, which provide a basis for its imaging appearances, prognosis, and treatment. This discussion is important for the general radiologist as the incidence of immunodeficiency-related PCNSL may be increasing.

CNS bridging radiotherapy achieves rapid cytoreduction before CAR T-cell therapy for aggressive B-cell lymphomas

AbstractChimeric antigen receptor (CAR) T-cell therapy (CART) for central nervous system lymphoma (CNSL) is a promising strategy, yet responses are frequently not durable. Bridging radiotherapy (BRT) is used for extracranial lymphoma in which it can improve CART outcomes through cytoreduction of high-risk lesions. We hypothesized that BRT would achieve similar, significant cytoreduction before CART for CNSL (CNS-BRT). We identified patients with CNSL with non-Hodgkin B-cell lymphoma who received CNS-BRT before commercial CART. Cytoreduction from CNS-BRT was calculated as change in lesion size before CART. Twelve patients received CNS-BRT, and the median follow-up among survivors is 11.8 months (interquartile range, 8.5-21.9). Ten patients had CNSL (9 secondary, 1 primary) and 2 patients had epidural disease (evaluable for toxicity). All 10 patients with CNSL had progressive disease at the time of CNS-BRT. Of 12 patients, 1 experienced grade ≥3 cytokine release syndrome, and 3 of 12 patients experienced grade ≥3 immune effector cell–associated neurotoxicity syndrome. CNS-BRT achieved a 74.0% (95% confidence interval, 62.0-86.0) mean reduction in lesion size from baseline (P = .014) at a median of 12 days from BRT completion and before CART infusion. Best CNS response included 8 complete responses, 1 partial response, and 1 progressive disease. Three patients experienced CNS relapse outside the BRT field. Preliminary data suggest CNS-BRT achieves rapid cytoreduction and is associated with a favorable CNS response and safety profile. These data support further study of BRT as a bridging modality for CNSL CART.

Primary central nervous system lymphomas in immunocompromised patients require specific response criteria.

Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed.