Search Results (66)

Background/Objectives: Short induction followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) is effective in newly diagnosed elderly patients with primary central nervous system lymphoma (PCNSL) but associated with significant toxicity. Geriatric assessments (GAs) may help to predict treatment risk and prognosis, yet no standardized GAs exist for PCNSL. Our aim was to evaluate the impact of GA on HCT-ASCT eligibility and survival. Methods: We analyzed 65 patients > 65 years treated in the MARiTA and MARTA studies. Treatment comprised 2 cycles of rituximab, HD-MTX and cytarabine followed by HCT-ASCT. GAs at diagnosis were analyzed for progression-free survival (PFS), overall survival (OS) and premature end of treatment (pEOT). Results: After median follow-up of 43 months, 12-month PFS/OS were 69.2% (95% CI 56.5–78.9%)/70.8% (58.1–80.2%) from diagnosis and 80.4% (66.6–88.9%)/84.3% (71.1–91.8%) from time of HCT-ASCT. ECOG PS ≥ 2, Lachs geriatric screening (Lachs) ≥30% and Cumulative Illness Rating Scale-Geriatric (CIRS-G) ≥6, ≥7 and ≥8, respectively, were significantly associated with pEOT in univariate analysis (UVA). In multivariate analysis (MVA), CIRS-G remained significant. A composite EBL score (ECOG PS ≥ 2, Barthel Index of Activities of Daily Living (Barthel) < 20, Lachs ≥ 30%) ≤1 predicted successful completion of HCT-ASCT in >90% of patients. ECOG PS ≥ 2 and Barthel < 20 were associated with decreased PFS and OS in UVA; ECOG PS ≥ 2 remained significant in MVA. Conclusions: This is the first study to link GA with treatment feasibility in elderly PCNSL patients undergoing intensive therapy. Our results will be validated in the PRIMA-CNS trial (EudraCT 2020-001181-10). Full article

We present the case of a patient with primary CNS lymphoma (PCNSL), with MYD88 and CD79B gene variants, who was unable to complete standard induction and consolidation treatment due to toxicity and co-morbidities after three cycles of MATRix. Although he had responded to truncated induction, acalabrutinib, the BTK inhibitor, was used in an attempt to consolidate and maintain his response. He has an ongoing remission at 18 months of follow-up. Following the case presentation, we provide a review of PCNSL, the evolution of therapy, and how BTK inhibitors are now emerging treatments incorporated into the salvage of relapsed and refractory disease and into first-line treatment in some clinical trials. This is the first reported case in the literature of acalabrutinib use for consolidation and maintenance of PCNSL. We hope this can support clinical trial design for BTKi use in this setting in the future. Full article

Background: Primary central nervous lymphoma (PCNSL) is a rare, aggressive, non-Hodgkin’s lymphoma. Outcomes are poor with standard induction of high-dose methotrexate (HD-MTX)-based regimens and consolidation. We present retrospective data from the Georgia Cancer Center. Methods: A single retrospective chart review was conducted on all PCNSL patients from 2013 to 2023 to assess for various factors influencing care. Results: Of a total of 38 PCNSL patients, 6 died and 2 were lost to follow-up prior to therapy initiation, leading to a total of 30 patients for analysis. The median age was 62.3 (21–82 years). One patient had HIV/AIDS. Two patients were on immunosuppression for either kidney transplant or multiple sclerosis (MS). The HIV and MS cases were Epstein-Barr Virus (EBV)-positive. Completion of ≥six cycles of induction was predictive of response. Conclusions: PCNSL remains an area of high unmet need. Recent studies have shown that HD-MTX-based therapy and autologous stem cell transplantation afterwards leads to improved outcomes regardless of age; however, non-relapse mortality is important to consider. Our data from a primarily elderly and sub-rural cohort reiterate the efficacy of combination chemoimmunotherapy and impact of induction cycle number on response, regardless of age. A multidisciplinary approach and targeted agent maintenance should be considered to improve outcomes in the elderly. Full article

Lymphomas involving the central nervous system (CNS) have worse outcomes, including both primary and secondary CNS lymphomas, which are associated with poorer overall survival outcomes. The World Health Organization classifies CNS lymphoma as arising from the brain, leptomeninges, and spinal cord, but this simplified CNS anatomical definition fails to incorporate areas of ambiguity that can be clinically relevant for treatment decision making. In this article, we review the anatomical boundaries of CNS lymphoma within select border-zone biological structures located at the CNS borders in order to gain a consensus working definition of CNS disease boundaries. We review anatomical localizations with border-zone CNS boundaries, including the dura, cavernous sinus, circumventricular organs, pituitary gland, and cranial nerves. Though some portions of the eye would be considered CNS and others extra-CNS, recommendations for this structure are outside the scope of this review. Through this review, we examine the impact of lymphomatous invasion on select CNS-bordering anatomical structures, aiming to better define treatment categorization as CNS or extra-CNS, with a focus on B cell lymphoma types. Full article

Background/Objectives: In Europe, over 80% of children diagnosed with cancer survive at least 5 years. To improve cancer monitoring, the Paediatric Population-Based Cancer Registry (PCRM) was established in the Community of Madrid. This study aimed to describe population-based 1-, 3- and 5-year survival for children and adolescents diagnosed with cancer, by sex, age, tumour type and stage at diagnosis. Methods: Data were extracted from the PCRM, which reviews all cases identified through integrated primary care, hospital discharge, and mortality data, using electronic medical records. Patients aged 0–19 diagnosed with primary malignant cancer between 2015 and 2018 were included, with follow-up for vital status through October 2024. Stage was classified using the 2014 Toronto Childhood Cancer Staging Guidelines (tier 2). Kaplan–Meier methods were used to estimate survival, and log-rank tests assessed group differences. Cox regression was used to quantify the effect of localized vs. advanced disease. Results: The analysis included 862 patients. Most frequent cancers were leukaemia (24.1%), lymphomas (22.2%) and central nervous system (CNS) tumours (12.6%). Stage was assigned to 88.4% tumours. Overall survival was 93.6% in 1 year and 85.9% in 5 years. Five-year survival was 83.7% for leukaemia, 97.4% for lymphomas, 66.1% for CNS tumours; 85.8% in boys vs. 85.9% in girls (p = 0.908); 85.2% in children aged 0–14 years vs. 87.8% in adolescents aged 15–19 years (p = 0.314); and 69.9% for advanced vs. 89.7% for early-stage (p < 0.001), with a 3.3-fold higher mortality risk. Conclusions: This population-based study offers promising survival estimates reaching 86% globally at 5 years while revealing differences by cancer type and stage. It also highlights the Toronto Guidelines as a valuable tool for standardizing cancer registry methods and providing useful epidemiological indicators. Full article

Background: Brain metastases (BMs) are a common and challenging complication of non-small cell lung cancer (NSCLC), historically associated with a poor prognosis. The development of targeted therapies, specifically tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations, has significantly improved treatment outcomes. Methods: This article reports and evaluates the efficacy of different generations of TKIs for NSCLC with BMs. The primary endpoints assessed are intracranial objective response rates (IC-ORR), progression-free survival (PFS), and overall survival (OS). The analysis considers TKIs as monotherapy and in combination with radiotherapy. It also examines the impact of newer generation TKIs with enhanced blood–brain barrier (BBB) penetration on intracranial control. The report further discusses the integration of systemic therapy with local modalities like stereotactic radiosurgery (SRS) and the safety profiles of these agents, including central nervous system (CNS) and metabolic adverse events. Results: Newer generation TKIs demonstrate significantly enhanced BBB penetration, resulting in superior intracranial control compared to older generations. These agents show remarkable intracranial activity, contributing to improved IC-ORR, PFS, and OS. The optimal integration of systemic therapy with local modalities, such as SRS, is still under investigation. Treatment with these TKIs is associated with distinct safety profiles, including novel CNS and metabolic adverse events, which require careful management due to prolonged treatment durations. Conclusions: The management of CNS metastases in NSCLC is evolving towards more proactive and personalized therapeutic strategies. Newer generation TKIs have profoundly reshaped the treatment landscape by offering superior intracranial control. Further research is needed to determine the optimal integration of these systemic therapies with local modalities and to effectively manage the associated adverse events. Full article

Neurolymphomatosis (NL) is a rare manifestation of hematologic malignancies, characterized by a neoplastic infiltration of the peripheral nervous system and cranial nerves (CNs). Non-Hodgkin lymphomas (NHLs) account for 90% of NL cases, while acute leukemia represents 10% of the cases. NL can occur as the first manifestation of a malignancy (primary), or as a relapse or progression of a previously treated disease (secondary). Herein, we report a unique case of NL involving the left orbit and CNs in a 74-year-old female with primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL). Our patient developed secondary neurolymphomatosis involving the left orbit and CNs II, III, V, and VI, supported by clinical, radiologic, and histologic findings. The lacrimal gland enhancement was histopathologically proven to be caused by the direct spread of CNS DLBCL to the lacrimal nerve, a branch of CN V, identifying NL as one of the conditions that can affect this organ. The lacrimal gland could be considered as a more accessible biopsy site when the involvement of CN V is suspected. Full article

Background: Leptomeningeal disease (LMD) is challenging to diagnose and monitor given the poor sensitivity of current gold-standard diagnostics. Cerebrospinal fluid tumor cells (CSF-TCs) have been studied as a biomarker for disease management because oncogene amplification of the primary, metastatic, and CNS metastatic tumors can be heterogeneous. The CNSide platform enumerates CSF-TCs and analyzes oncogene expression via immunocytochemistry (ICC), fluorescent in situ hybridization (FISH), and next-generation sequencing (NGS). We report the utility of this combined enumerative and mutational testing for LMD diagnosis and disease monitoring. Methods: A multicenter, retrospective analysis of commercially ordered assays from two health systems between January 2020 and July 2023 included 613 tests on 218 individual patients with suspected or confirmed LMD. To date, this is the largest cohort of patients in LMD literature evaluated using CSF-TCs. Results: CSF-TCs were detected in 67% (412/613) of samples. The most analyzed cancer types were breast (n = 105) and lung (n = 65). In lung cancer, anaplastic lymphoma kinase (ALK) was detected in 14% (17/118), and c-MET was detected in 61% (78/128). In breast cancer, HER2 was detected in 39% (65/168), and estrogen receptor (ER) was detected in 26% (44/168). Sixty-six patients underwent 2+ longitudinal CSF draws; among these, there were 58 flips in oncogene detection over time, and 30% (20/66) of patients had at least one biomarker change in the CSF. Conclusions: Longitudinal combined ICC/FISH/NGS CSF testing demonstrates a wide range in CSF-TC enumeration, which may be correlated with clinical course, and furthermore identifies actionable tumor markers that frequently fluctuate over time. Utilization of this platform would enable timely, personalized LMD-specific chemotherapy. Full article

Evaluating altered mental status and suspected meningeal disorders in children often begins with imaging, typically before a lumbar puncture. The challenge is that meningeal enhancement is a common finding across a range of pathologies, making diagnosis complex. This review proposes a categorization of meningeal diseases based on their predominant imaging characteristics. It includes a detailed description of the clinical and imaging features of various conditions that lead to leptomeningeal or pachymeningeal enhancement in children and adolescents. These conditions encompass infectious meningitis (viral, bacterial, tuberculous, algal, and fungal), autoimmune diseases (such as anti-MOG demyelination, neurosarcoidosis, Guillain-Barré syndrome, idiopathic hypertrophic pachymeningitis, and NMDA-related encephalitis), primary and secondary tumors (including diffuse glioneuronal tumor of childhood, primary CNS rhabdomyosarcoma, primary CNS tumoral metastasis, extracranial tumor metastasis, and lymphoma), tumor-like diseases (Langerhans cell histiocytosis and ALK-positive histiocytosis), vascular causes (such as pial angiomatosis, ANCA-related vasculitis, and Moyamoya disease), and other disorders like spontaneous intracranial hypotension and posterior reversible encephalopathy syndrome. Despite the nonspecific nature of imaging findings associated with meningeal lesions, narrowing down the differential diagnoses is crucial, as each condition requires a tailored and specific treatment approach. Full article

The advent of chimeric antigen receptor (CAR)-T cells has recently changed the prognosis of relapsing/refractory diffuse large B-cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood–brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR-T cells observed in systemic B-cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers. Early studies conducted in adult and paediatric patients with solid CNS tumours reported a distinct profile of neurotoxicity referred to as Tumour inflammation-associated neurotoxicity (TIAN), corresponding to local inflammation at the tumour site manifesting with focal neurological deficits or mechanical complications (e.g., obstructive hydrocephalus). The present review summarises available data on the efficacy and safety of CAR-T cells for solid and haematological CNS malignancies, emphasising known and emerging phenotypes, ongoing challenges, and future perspectives. Full article

Novel therapies such as CAR-T, BTK inhibitors and PD-1 inhibitors have changed the management of aggressive B-cell lymphomas. Nonetheless, these novel therapies have their own risk of late toxicities including second malignancies. They also create a subgroup of patients with relapse, treatment failure, or indefinite maintenance. We discuss the current role of autologous and allogeneic stem cell transplantation in this context. In patients with recurrent diffuse large B-cell lymphoma, CAR-T cell treatment has largely replaced autologous transplant. Autologous transplant should be considered in patients with late relapses and in selected patients with T-cell-rich B-cell lymphoma, where CAR-T cell therapy may be less effective. It also remains the treatment of choice for consolidation of patients with primary CNS lymphoma. In mantle cell lymphoma, intensive chemotherapy combined with BTK inhibitors and rituximab results in excellent outcomes, and the role of autologous transplantation is declining. In Hodgkin’s lymphoma, autologous transplant consolidation remains the standard of care for patients who failed initial chemotherapy. Allogeneic transplantation has lower relapse rates but more complications and higher non-relapse mortality than autologous transplantation. It is usually reserved for patients who fail autologous transplantation or in whom autologous stem cells cannot be collected. It may also have an important role in patients who fail CAR-T therapies. The increasing complexity of care and evolving sequencing of therapies for patients with aggressive B-cell lymphomas only emphasizes the importance of appropriate patient selection and optimal timing of stem cell transplantation. Full article

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. Full article

Background: The incidence of lymphomatous involvement of the central nervous system (CNS) has been increasing in recent years. However, the rarity of the disease has resulted in a scarcity of available data regarding its clinical presentation, natural history, and prognosis. We aimed to investigate the neurological characteristics of uncommon lymphomatous involvements confined to the CNS and to identify key variables that could serve as predictive biomarkers for treatment outcomes. Methods: We identified patients presenting with neurological symptoms and diagnosed with CNS-restricted lymphomatous involvement between 2005 and 2023. Results: We identified 44 cases, 93% of which were diagnosed with primary central nervous system lymphoma (PCNSL) and 7% with intravascular lymphoma. The median time from symptom onset to diagnosis was 47 days (range: 6–573 days), with no statistically significant difference between patients older and younger than 60 years (p = 0.22). The median follow-up time was 1144 days (range: 27–3501 days). Cognitive deterioration was the most common presenting symptom, occurring in 19 out of 44 patients (43%). Brain MRI revealed that lobar lesions were the most frequent location of lesions, found in 24 out of 44 patients (55%). By the end of the study period, 30 patients (68%) had died, with a median survival of 666 days (range: 17–3291 days). Death was significantly more common in patients who experienced relapses (p = 0.04; 95% CI: 0.99–0.03), with these patients having a four times higher chance of death (HR = 4.1; 95% CI: 1.01–16.09). The time to diagnosis significantly correlated with survival (p = 0.02; 95% CI: 0.005–0.54), as did the Eastern Cooperative Oncology Group (ECOG) performance status at the last follow-up (p = 0.006; 95% CI: 0.0012–0.62). Patients aged over 60 years did not exhibit a higher likelihood of death (p = 0.19; HR = 2.3; 95% CI: 0.63–8.61); however, the threshold age at diagnosis for the maximally predicted mortality was 64 years (ROC = 0.73; p = 0.03). Conclusions: Patients had significant delays in diagnosis, affecting patient outcomes. Cognitive deterioration and lobar lesions were prominent clinical and radiological features. Mortality was notably higher in patients with relapses and those who had a longer time to diagnosis. Full article

Background: 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. Methods: 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. Results: 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. Conclusion: The study demonstrated that the PW score was an effective prognostic indicator for identifying post-treatment primary CNS lymphoma patients with worse outcomes. Full article

Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p = 0.029). CDKN2A HD was associated with a shorter OS (p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients. Full article