Search Results (111)

To deliver the most effective cancer treatment, clinicians require rapid and accurate diagnoses that delineate tumor type, stage, and prognosis. Consequently, minimizing the need for repetitive and invasive procedures like biopsies and myelograms, along with their associated risks, is a critical challenge. Non-invasive monitoring offers a promising avenue for tumor detection, screening, and prognostication. While the identification of oncogenes and biomarkers from circulating tumor cells or tissue biopsies is currently standard practice for cancer diagnosis and classification, accumulating evidence underscores the significant role of epigenetics in regulating stem cell fate, including proliferation, self-renewal, and malignant transformation. This highlights the importance of analyzing the methylome, exosomes, and circulating RNA for detecting cellular transformation. The development of diagnostic assays that integrate liquid biopsies with epigenetic analysis holds immense potential for revolutionizing tumor management by enabling rapid, non-invasive diagnosis, real-time monitoring, and personalized treatment decisions. This review covers current studies exploring the use of epigenetic regulation, specifically the methylome and circulating RNA, as diagnostic tools derived from liquid biopsies. This approach shows promise in facilitating the differentiation between primary central nervous system lymphoma and other central nervous system tumors and may enable the detection and monitoring of acute myeloid/lymphoid leukemia. We also discuss the current limitations hindering the rapid clinical translation of these technologies. Full article

Background: The gold standard for diagnosing primary central nervous system lymphoma (PCNSL) is brain biopsy, an invasive procedure with significant risks. The role of cerebrospinal fluid (CSF) examination, limited to cytology and flow cytometry in current practice, is acknowledged as a less invasive diagnostic method. We aimed to summarize available data concerning the efficacy and actual use of current standard CSF diagnostics in the diagnosis of PCNSL. Methods: A systematic review and meta-analysis of 144 studies (n = 9493 patients) was conducted, assessing detection rates of cytology and flow cytometry and the proportion of diagnoses based on CSF analysis. The QUADAS-2 tool was used to evaluate study quality and bias. Results: Meta-analysis showed an 18% pooled detection rate for positive CSF results, with 17% for cytology and 20% for flow cytometry. Only 8% of diagnoses were made using CSF analysis. Most studies had a high risk of bias. Conclusions: Despite its established role in guidelines, CSF analysis remains underutilized for diagnosing PCNSL, with room to improve its clinical impact. Novel techniques, such as chemokines and circulating tumor DNA (cfDNA) analysis, hold promise to unlock the untapped potential of CSF diagnostics, offering significant advancements in non-invasive PCNSL diagnosis. Full article

Brain metastases (BMs) are the most common intracranial tumors in adults. Their heterogeneity, potential multifocality, and complex biomolecular behavior pose significant diagnostic and therapeutic challenges. Artificial intelligence (AI) has the potential to revolutionize BM diagnosis by facilitating early lesion detection, precise imaging segmentation, and non-invasive molecular characterization. Machine learning (ML) and deep learning (DL) models have shown promising results in differentiating BMs from other intracranial tumors with similar imaging characteristics—such as gliomas and primary central nervous system lymphomas (PCNSLs)—and predicting tumor features (e.g., genetic mutations) that can guide individualized and targeted therapies. Intraoperatively, AI-driven systems can enable optimal tumor resection by integrating functional brain maps into preoperative imaging, thus facilitating the identification and safeguarding of eloquent brain regions through augmented reality (AR)-assisted neuronavigation. Even postoperatively, AI can be instrumental for radiotherapy planning personalization through the optimization of dose distribution, maximizing disease control while minimizing adjacent healthy tissue damage. Applications in systemic chemo- and immunotherapy include predictive insights into treatment responses; AI can analyze genomic and radiomic features to facilitate the selection of the most suitable, patient-specific treatment regimen, especially for those whose disease demonstrates specific genetic profiles such as epidermal growth factor receptor mutations (e.g., EGFR, HER2). Moreover, AI-based prognostic models can significantly ameliorate survival and recurrence risk prediction, further contributing to follow-up strategy personalization. Despite these advancements and the promising landscape, multiple challenges—including data availability and variability, decision-making interpretability, and ethical, legal, and regulatory concerns—limit the broader implementation of AI into the everyday clinical management of BMs. Future endeavors should thus prioritize the development of generalized AI models, the combination of large and diverse datasets, and the integration of clinical and molecular data into imaging, in an effort to maximally enhance the clinical application of AI in BM care and optimize patient outcomes. Full article

Background/Objectives: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive tumor, primarily affecting elderly patients. Radiotherapy (RT) remains an important treatment option, particularly for patients who are ineligible for systemic chemotherapy. This study aims to identify prognostic factors and evaluate recurrence patterns in a real-world cohort of PCNSL patients treated with RT. Methods: We retrospectively analyzed 64 PCNSL patients treated with radiotherapy at our institution between 2000 and 2022. Clinical characteristics, treatment details, and outcomes were collected by chart review. Overall survival (OS) was analyzed using Kaplan–Meier and Cox regression methods. Recurrence patterns were assessed based on available post-treatment imaging. Results: Median patient age was 71 years (range: 31–83); 53.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Radiotherapy was used as first-line treatment in 62.5% of cases, primarily due to contraindications to chemotherapy. Median OS was 10 months from diagnosis. Age, poor performance status, seizures at presentation, absence of systemic therapy, incomplete radiotherapy, and <80% applied dose of planned radiotherapy were associated with inferior OS in our univariable analysis. Multivariable analysis confirmed age, systemic therapy, seizures, and radiotherapy dose <80% as independent predictors. Among twenty-nine patients with imaging follow-up, eight recurrences after RT were documented: six of those within, and two outside of the initially affected areas. All recurrences occurred within previously irradiated areas. Conclusions: This study confirms known negative prognostic factors in PCNSL and underscores the importance of systemic chemotherapy for curatively intended treatments aiming for prolonged survival. The recurrence patterns observed question the added benefit of whole-brain irradiation in preventing distant relapses. These findings support the need for prospective trials to optimize radiotherapy strategies while balancing efficacy and neurotoxicity. Full article

Liquid biopsy through the analysis of circulating tumor DNA (ctDNA) is emerging as a powerful and non-invasive tool complementing tissue biopsy in lymphoma management. Whilst tissue biopsy remains the diagnostic gold standard, it fails to detect the molecular heterogeneity of the tumor’s multiple compartments and poses challenges for sequential disease monitoring. In diffuse large-B-cell lymphoma (DLBCL), ctDNA facilitates non-invasive genotyping by identifying hallmark mutations (e.g., MYD88, CD79B, EZH2), enabling molecular cluster classification. Dynamic changes in ctDNA levels during DLBCL treatment correlate strongly with progression-free survival and overall survival, underscoring its value as a predictive and prognostic biomarker. In Hodgkin’s lymphoma, characterized by a scarcity of malignant cells in tissue biopsies, ctDNA provides reliable molecular insights into tumor biology, response to therapy, and relapse risk. In primary central nervous system lymphoma, the detection of MYD88 L265P in ctDNA offers a highly sensitive, specific, and minimally invasive diagnostic option. Likewise, in aggressive T-cell lymphomas, ctDNA supports molecular profiling, aligns with tumor burden, and shows high concordance with tissue-based results. Ongoing and future clinical trials will be critical for validating and standardizing ctDNA applications, ultimately integrating liquid biopsy into routine clinical practice and enabling more personalized and dynamic lymphoma care. Full article

Background/Objectives: This population-based study examined epidemiological trends of primary cancers in adolescents and young adults (AYAs) to enhance the understanding of the specific spectrum of cancers impacting AYAs in Belgium. Methods: Data on incidence, prevalence, mortality, and survival were obtained from the Belgian Cancer Registry (2004–2020, N = 43,535). (A)APC statistics were compared with children (5–14 years) and adults (40–49 years). Results: Cancer incidence increased by 0.4% annually from 66 to 80 per 100,000 person-years (ESR2013) but stabilised after 2015, except for Hodgkin lymphoma, chronic myeloid neoplasms, and testicular and breast cancer, which continued to rise. Mortality decreased by 1% annually, from 10 to 7 per 100,000 person-years (2004–2019). Five-year relative survival (RS) was 87% but remained low for certain cancers, including ovary (78%), central nervous system (67%), precursor haematopoietic neoplasms (64%), gastrointestinal (excl. colorectal) (49%), and lung-bronchus-trachea cancers (42%). Conclusions: From 2004–2020, the cancer burden among AYAs in Belgium increased due to improved survival, while incidence stabilised after 2015. Five-year RS exceeds 80% overall but remains lower for some cancers compared to children (e.g., precursor haematopoietic neoplasms) or older adults (e.g., breast cancer, sarcoma). The Belgian epidemiological trends align with those in neighbouring countries (Netherlands, France, Germany). 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/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. Full article

Introduction: Treatment for primary central nervous system lymphoma (PCNSL) includes high-dose methotrexate (HD-MTX)-based systemic therapy. Multiple regimens exist with no clear standard of care. We evaluated the impact of different therapies on PCNSL outcomes at a single institution. Materials and Methods: A total of 95 consecutive patients with PCNSL from 2002 to 2021 were retrospectively reviewed. The overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method. The log-rank test and univariate and multivariable Cox regression analysis were used to evaluate the relationship between clinicopathologic and treatment variables with outcomes. Results: Among the 62 patients treated with definitive systemic therapy, the median age was 58; 71% had a Karnofsky performance status > 70, 49% had a single lesion, 31% received HD-MTX alone, and 61% had HD-MTX + rituximab. The two-year OS and PFS were 64% (95% CI: 49.8–75.0%) and 49% (95% CI: 35.0–60.9%), respectively. On multivariable analysis, the completion of > six cycles of HD-MTX (HR 0.40; 95% CI: 0.21–0.76; p = 0.01) was associated with superior OS, while the use of rituximab was associated with inferior OS (HR 2.82; 95% CI: 1.37–5.83; p = 0.01). There were no significant associations between the OS and PFS with temozolomide, the extent of surgical resection, radiation, or the size or number of initial lesions (all p > 0.05). Discussion: Innovation is needed to improve the outcomes for patients with PCNSL. Full article

Background: Some evidence of the value of 18F-fluorodesoxyglucose ([18F]FDG) positron emission tomography (PET) imaging for the assessment of gliomas and glioblastomas (GBMs) is emerging. The aim of this systematic review was to assess the role of [18F]FDG PET-based radiomics and machine learning (ML) in the evaluation of these neoplasms. Methods: A wide literature search of the PubMed/MEDLINE, Scopus, and Cochrane Library databases was made to find relevant published articles on the role of [18F]FDG PET-based radiomics and ML for the assessment of gliomas and GBMs. Results: Eight studies were included in the systematic review. Signatures, including radiomics analysis and ML, generally demonstrated a possible diagnostic value to assess different characteristics of gliomas and GBMs, such as the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter, the isocitrate dehydrogenase (IDH) genotype, alpha thalassemia/mental retardation X-linked (ATRX) mutation status, proliferative activity, differential diagnosis with solitary brain metastases or primary central nervous system lymphoma, and prognosis of these patients. Conclusion: Despite some intrinsic limitations of radiomics and ML affecting the studies included in the review, some initial insights on the promising role of these technologies for the assessment of gliomas and GBMs are emerging. Validation of these preliminary findings in multicentric studies is needed to translate radiomics and ML approaches in the clinical setting. Full article

Background: Cerebral intra-arterial chemotherapy (CIAC) has been demonstrated to achieve tumoricidal concentrations in cerebral tumour cells that are otherwise unachievable due to the presence of the blood–brain barrier. In this study, we sought to analyze the safety of CIAC in a cohort of patients treated at the Centre intégré universitaire de santé et de services sociaux de l’Estrie—Centre hospitalier universitaire de Sherbrooke (CIUSSS-CHUS). Methods: Treatments consisted of monthly CIAC. A neurological examination and neuroimaging study (MRI) were performed before every treatment. The files of patients enrolled in our CIAC programme were reviewed. Adverse events were analyzed and categorized. Results: Overall, 2991 CIAC procedures were performed in 642 patients. Pathologies were as follows: malignant gliomas (68.7%), cerebral metastasis (17.6%), and cerebral lymphomas (13.7%). Perfusion vessels were as follows: 80% internal carotid artery and 20% vertebral artery. The chemotherapeutic agents used were carboplatin (86.4%), methotrexate (28.5%), melphalan (28.6%), and liposomal doxorubicin (2.8%). Osmotic blood–brain barrier disruption (BBBD) was induced in 30.5% of treatments. Symptomatic vascular adverse events occurred during 27 procedures (0.9%) in 26 patients (4%). Namely, 23 strokes, one carotid artery occlusion (responsible for one of the strokes), and two intratumoral and one subdural hemorrhage. The absolute risk of stroke was 1.3% and 0.5% for CIAC with or without BBBD, respectively. The use of the vertebral artery significantly increased the risk of stroke. Drug infusion-related seizures occurred in 2.5% of patients; 83.8% were associated with methotrexate and 16.2% with carboplatin. Conclusions: CIAC is a safe procedure with a 0.9% overall rate of symptomatic complications (stroke, carotid occlusion, subdural hemorrhage or intratumoral bleeding—n = 27/2991) on a treatment basis, mainly consisting of strokes (85%, n = 23), with a modified NIH Stroke Scale score of 4.1 ± 3.3. 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

Objectives: This article reports a rare case of primary central nervous system lymphoma (PCNSL) found in a patient with thyroid cancer after surgery. Methods: The patient was initially misdiagnosed with brain metastases, and the diagnosis of PCNSL was later confirmed by pathology. Results: The analysis of this case and review of the relevant literature explores the possible mechanisms of the coexistence of thyroid cancer and PCNSL, as well as their diagnostic, differential diagnostic, and therapeutic challenges. Conclusions: The article suggests a possible correlation between the coexistence of multiple cancers and autoimmune diseases and emphasizes that disease cannot be only considered in a monolithic way. Full article

Sjögren’s disease (SjD), or primary Sjögren’s syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin’s lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sjögren’s Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren’s syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sjögren’s disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sjögren’s disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords ‘Sjögren’s syndrome’ OR ‘Sjögren’s disease’ AND ‘gastroesophageal reflux disease’ AND ‘microbiota’ OR microbiota dysbiosis’. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sjögren’s disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sjögren’s disease and the personalized management of the disease. Full article