Liquid biopsy for CNS lymphoma: CSF exosomes and CSF exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b are promising biomarkers for diagnosis.

BACKGROUND: Central nervous system lymphoma (CNSL) is a devastating disease with a poor prognosis. Early diagnosis, monitoring of the treatment response, and outcome prediction carry the utmost importance in the management of patients with CNSL. Surgical biopsy is the gold standard for tissue diagnosis, however, this procedure has potential complications. Therefore, there is a need for a method that provides information about diagnosis and patient monitoring to avoid surgical risks. The study aimed to investigate potential diagnostic biomarkers for patients with CNSL. METHODS AND RESULTS: Patients with secondary CNSL were included in this study. Serum and cerebrospinal fluid (CSF) samples were collected before treatment and after completion of the treatment. Cell-free DNA (cfDNA), exosomes, free and exosomal microRNA (miR)-15a, miR-21, miR-155, miR-210, and miR-19b in both serum and CSF were examined, and they were compared with the controls. Also, their levels before and after treatment were compared. Nine patients with the diagnosis of secondary CNSL were reviewed. cfDNA, miR-15a, and miR-155 in serum, and exosome in CSF were found to be significantly higher in CNSL patients compared to the controls. Exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b in CSF were found to be significantly higher in CNSL patients compared to controls, whereas their levels in serum were not significantly high. CONCLUSIONS: Our findings suggested that exosomes and exosomal miR-15a, miR-21, miR-155, miR-210 and miR-19b in CSF would be promising biomarkers for the diagnosis of patients with CNSL. Further studies are needed to confirm our findings.

-New frontiers in domain-inspired radiomics and radiogenomics: increasing role of molecular diagnostics in CNS tumor classification and grading following WHO CNS-5 updates.

Gliomas and Glioblastomas represent a significant portion of central nervous system (CNS) tumors associated with high mortality rates and variable prognosis. In 2021, the World Health Organization (WHO) updated its Glioma classification criteria, most notably incorporating molecular markers including CDKN2A/B homozygous deletion, TERT promoter mutation, EGFR amplification, + 7/-10 chromosome copy number changes, and others into the grading and classification of adult and pediatric Gliomas. The inclusion of these markers and the corresponding introduction of new Glioma subtypes has allowed for more specific tailoring of clinical interventions and has inspired a new wave of Radiogenomic studies seeking to leverage medical imaging information to explore the diagnostic and prognostic implications of these new biomarkers. Radiomics, deep learning, and combined approaches have enabled the development of powerful computational tools for MRI analysis correlating imaging characteristics with various molecular biomarkers integrated into the updated WHO CNS-5 guidelines. Recent studies have leveraged these methods to accurately classify Gliomas in accordance with these updated molecular-based criteria based solely on non-invasive MRI, demonstrating the great promise of Radiogenomic tools. In this review, we explore the relative benefits and drawbacks of these computational frameworks and highlight the technical and clinical innovations presented by recent studies in the landscape of fast evolving molecular-based Glioma subtyping. Furthermore, the potential benefits and challenges of incorporating these tools into routine radiological workflows, aiming to enhance patient care and optimize clinical outcomes in the evolving field of CNS tumor management, have been highlighted.

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2017 and 2021, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 25.34 per 100,000 population (malignant AAAIR=6.89 and non-malignant AAAIR=18.46). This overall rate was higher in females compared to males (28.77 versus 21.78 per 100,000) and non-Hispanic Black persons compared to persons who were non-Hispanic White (26.60 versus 25.72 per 100,000), non-Hispanic American Indian/Alaska Native (23.48 per 100,000), non-Hispanic Asian or Pacific Islander (19.86 per 100,000), and Hispanic persons of all races (22.37 per 100,000). Gliomas accounted for 22.9% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.9% of all tumors and 51.5% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (41.7% of all tumors and 56.8% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.02 per 100,000 population. There were 87,053 deaths attributed to malignant brain and other CNS tumors between 2017 and 2021. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 17,411 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 35.7%. For a non-malignant brain or other CNS tumor the five-year relative survival rate was 92.0%.

Comment on, "Creactive protein levels, the prognostic nutritional index, and the lactate dehydrogenasetolymphocyte ratio are important prognostic factors in primary central nervous system lymphoma: a singlecenter study of 223 patients".

This study by Zuo et al. (2024) investigates the prognostic significance of C-reactive protein (CRP) levels, the prognostic nutritional index (PNI), and the lactate dehydrogenase-to-lymphocyte ratio (LLR) in primary central nervous system lymphoma (PCNSL) using data from 223 patients. The research demonstrates that these markers are critical in predicting patient outcomes, offering novel insights beyond traditional prognostic models like the MSKCC and IELSG scores. Despite its strengths, the study's retrospective design and lack of validation cohort limit its generalizability. Future research should focus on validating these findings in diverse, multicenter settings and integrating these markers with existing prognostic models to improve clinical decision-making. Longitudinal studies and advanced statistical methods are recommended to further explore the interactions between these factors and their impact on patient outcomes, potentially leading to the development of targeted therapies for PCNSL.

Comment on, "Longterm outcome and quality of life after CNS cavernoma resection: eloquent vs. noneloquent areas".

The study titled "Long-term outcome and quality of life after CNS cavernoma resection: eloquent vs. non-eloquent areas," by Shoubash et al. (2022) provides crucial insights into the long-term neurological outcomes and quality of life (QoL) in patients following CNS cavernoma resection. Differentiating between eloquent and non-eloquent areas, the study shows that patients generally experience non-inferior QoL, with some differences in physical role functioning. Utilizing the Short Form-12 (SF12) questionnaire at a mean follow-up of 6.5 years, the study's findings are significant for clinical decision-making and patient counseling. However, the study's small sample size and retrospective design limit its generalizability and introduce potential biases. The lack of preoperative QoL assessments further constrains its conclusions. Future research should focus on larger, prospective studies with comprehensive QoL metrics and longitudinal follow-up to better understand the impact of surgery on patient outcomes and improve clinical strategies.

Primary Central Nervous System Burkitt's Lymphoma in a Pediatric Patient: A Case Report and Literature Review.

OBJECTIVE: The objective of this research is to examine the therapy and outlook of pediatric primary central nervous system Burkitt lymphomas. METHODS: This study involves a retrospective analysis of the clinical data of a child with primary central nervous system Burkitt lymphoma who underwent treatment in our department. In addition, pertinent literature was reviewed to provide a comprehensive understanding of the topic. RESULTS: The patient was admitted to the neurosurgery department with symptoms of headache and vomiting. Brain magnetic resonance imaging (MRI) revealed multiple lesions in the right frontal and temporal lobes, dorsal thalamus, and posterior medulla oblongata. Most of the tumor mass was surgically removed from the right ventricle and diagnosed as Burkitt lymphoma. Abnormal lymph nodes were not found outside of the central nervous system. The patient achieved complete remission (CR) after receiving 6 cycles of treatment (R-AA-BB-CC-AA-BB-CC) based on the regimen of the Southern Pediatric Non-Hodgkin Lymphoma Treatment Collaboration Group 2017. As of November 23, 2023, the patient remained alive with no evidence of recurrence. CONCLUSIONS: Primary central nervous system Burkitt lymphoma is rare in children, and there is no universally accepted treatment protocol. However, the regimen outlined by the South China Children's Cancer Group-Non-Hodgkin Lymphoma in 2017 (SCCCG-NHL-2017) can serve as a useful reference for treating pediatric non-Hodgkin lymphoma.

Research on the comprehensive child life intervention program (CCLIP) for adjusting medical fear in children with central nervous system (CNS) cancers: a randomized controlled trial study protocol.

BACKGROUND: Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children's quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. METHODS: This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. DISCUSSION: This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. TRIAL REGISTRATION: This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Characterizing second line and beyond therapies for primary central nervous system lymphomas.

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare and aggressive lymphoma that affects the CNS without other systemic involvement. High-dose methotrexate (HDMTX)-based regimens are recommended frontline treatment, followed by consolidation with either high-dose chemotherapy, whole brain radiation (WBRT) +/- sequential temozolomide (TMZ), or autologous stem cell transplant (autoSCT). Despite advancements with HDMTX and rituximab, up to half of patients will relapse. Treatment for relapsed or refractory (R/R) disease varies widely as preferred regimens are not well-established. Our study aimed to provide real-world characterization of R/R PCNSL therapies. The secondary objective was characterization of consolidation methods after frontline treatment. This retrospective, descriptive analysis included 54 adult PCNSL patients that received a HDMTX-based frontline regimen between 4/1/2016 and 7/1/2022. Patients receiving HDMTX for the purpose of secondary CNS lymphoma, non-B cell origin PCNSL, and intraocular lymphoma were excluded. Thirty-one patients (57%) received consolidation therapy with rituximab and high-dose cytarabine (R-HDAC), WBRT, or both. Thirteen patients (24%) proceeded with autoSCT. Twenty-five patients had disease progression, with 17 patients receiving second line treatment. The second line treatments were WBRT (24%), clinical trial (18%), rituximab with lenalidomide (R2; 18%), re-induction with HDMTX-based regimens (18%), ibrutinib with rituximab (12%) and R-HDAC (12%). Seven patients progressed, and all received third line treatment. Treatments varied, including R2; ibrutinib +/- HDMTX; rituximab, methotrexate, and cytarabine; R-HDAC; R-nivolumab; and WBRT. Five patients received a fourth line regimen of R +/- lenalidomide, R-HDMTX, or nivolumab monotherapy. Regimens used for the three patients who received fifth line treatment and beyond included R-TMZ and pembrolizumab monotherapy in addition to previously described regimens. Regimen selection is varied and highly dependent on physician preference and patient factors, including clinical trial eligibility, prior therapies, performance status, organ function, and treatment intent. Prospective clinical trials are needed to guide optimal management.

Impact on natural history of atypical meningioma after changes in 2016 edition of the world health organization (WHO) classification of central nervous system tumors: a literature review.

Meningiomas and their WHO histological diagnostic criteria is complex, especially for grade 2 tumors presenting a interobserver discordance as high as 12.2%. The 2016 edition of the WHO Classification of CNS tumors recommended brain invasion as a stand-alone grading criterion for diagnosing an atypical grade 2 meningioma (AM). To provide an overview of the classification of 2016 WHO impact on the natural history of atypical meningioma (AM) relative to previous classification. To achieve this goal, we selected articles from the period 2017-2024 in Medline search on atypical meningiomas and analyzed them after following the following criteria: 1) reports with confirmed histopathological diagnosis according to WHO 2016 and or 2021 criteria; 2) series and case reports; 3) detailed and individualized clinical outcomes for AM; and 4) papers written in English; after that a total of 3445 patients reported in 67 manuscripts from worldwide centers from 2017 to March 2024 were analyzed. The patient's age at the time of surgery ranged from 1 month to 97 years (mean 52.28 ± 18.7 years). The most common tumor site was the convexity, accounting for 67.8%, followed by the skull base in 30.6%, ventricle in 1%, and spine in 0.6%; Gross total resection (GTR) was performed in 71.25% and subtotal resection (STR) in 28.75%; 1021 patients (29.63%) underwent adjuvant radiotherapy, and 22 patients (0.6%) were treated with adjuvant chemotherapy; tumor recurrence was reported in 1221 patients (35.44%) and 859 deaths (24.93%). 1) AM prevalence in females; 2) AM age distribution similar to the distribution of meningiomas in general; 3) AM recurrence rate of 35.44%, despite the high rate of GTR, which was higher than previously reported; 4) deepening knowledge in molecular mechanism of tumor progression will provide alternative therapeutic approaches for AM.

Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma.

BACKGROUND/AIM: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination. PATIENTS AND METHODS: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC). RESULTS: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination. CONCLUSION: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies.

Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors.

The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.

AB008. Intramedullary spinal cord metastases in breast cancer with multiple central nervous system (CNS) metastases: a case report.

BACKGROUND: Although vertebral and epidural metastases are common, intramedullary metastases are rare. Intramedullary spinal cord metastases (ISCM) account for only 0.1-0.4% of metastasis tumors. About 26.5% of the tumour primaries are from breast cancer. Due to rapid neurological deficit deterioration, followed by short life expectancy, early diagnosis should be made to treat the tumor as any other central nervous system (CNS) metastases. CASE DESCRIPTION: A 50-year-old woman with a history of invasive ductal breast carcinoma, T2N3M0, grade III, luminal B (ER and HER2 positive) subtype who had previously undergone a mastectomy, presented with 1 month onset of bilateral leg weakness and sphincter compromise. The symptoms preceded by a burning sensation in the buttocks radiate to both legs. There was a history of dizziness and diplopia. Neurological examination showed paraparesis with hyperreflexia, hypoesthesia below L1 dermatome distribution, lateral gaze palsy of the right eye and hemifacial sensory deficit. A whole spine magnetic resonance imaging (MRI) shows multiple intramedullar enhancing lesions at the level of C4, C6, T2-T7, conus medullaris, and cauda equina. Brain MRI revealed multiple lesions in left hemicerebellum and temporal lobe with diffuse meningeal enhancement. The patient completed 5-fractionated 20 Gy whole spine radiotherapy with corticosteroid as an adjunct, followed by 30 Gy whole brain radiotherapy. At the 2-month follow-up, the motor weakness worsened and her clinical condition continued to deteriorate with multiple systemic complications until she died 3 months after ISCM diagnosis. CONCLUSIONS: ISCM is associated with aggressive progression. Only 1-year span from breast cancer until the patient is diagnosed with ISCM. Although CNS metastases are mostly found in HER2-positive breast cancers, data on ISCM is still limited. Most cases of ISCM have additional CNS metastases, leading to severe neurological deficits up to life-threatening conditions. A clear standard therapeutic protocol for ISCM has not yet been defined. Widespread metastasis and systemic disease progression were the main cause of death. The treatment goal is to preserve neurological function and improve patient's quality of life. Studies to generate evidence-based data with an algorithm to choose an appropriate treatment for ISCM is needed.

AB021. Primary diffuse large B-cell lymphoma of the central nervous system: role of imaging in a rare disease-a case report.

BACKGROUND: Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) constitutes approximately 1-3% of primary CNS tumors. This rare CNS tumor presents diverse clinical manifestations and variable imaging characteristics, making its diagnosis challenging using radiological modalities alone. Recognizing the role of imaging in different stages of treatment and understanding the various imaging patterns and radiological features is crucial for timely diagnosis and appropriate therapeutic decision-making. CASE DESCRIPTION: A 62-year-old woman presented to our tertiary hospital with a 1-month history of left-sided headache and left hemiparesis. A computed tomography (CT) scan from a previous hospital revealed a space-occupying lesion in the right temporo-occipital region with signs of increased intracranial pressure but no evidence of hemorrhage or calcifications. Subsequent magnetic resonance imaging (MRI) demonstrated a solid intra-axial lesion in the right temporoparietooccipital region, which exhibited heterogeneous enhancement with diffusion restriction. The lesion appeared hypointense on T1-weighted and hyperintense on T2-fluid attenuated inversion recovery (T2-FLAIR) sequence, containing cystic components surrounded by edema and causing compression of the occipital horn of the right lateral ventricle without midline shift. Immunohistochemical analysis confirmed the diagnosis of high-grade DLCBL. The patient underwent surgical resection followed by chemotherapy. A follow-up MRI revealed a new lesion in the right temporoparietooccipital region, which had increased in size, suggestive of lymphoma recurrence. The variable radiological presentations of primary CNS lymphoma (PCNSL) can often mimic other pathologies, such as gliomas, infections, abscesses, and secondary lymphomas, making it a diagnostic challenge. The imaging findings in this case align with the typical features of PCNSL. Both initial and follow-up imaging played a crucial role in guiding therapeutic decisions and assessing treatment response. CONCLUSIONS: This case report underscores the importance of recognizing the imaging characteristics of primary DLBCL of the CNS. Timely and accurate diagnosis based on imaging patterns is essential for expediting therapeutic decisions and evaluating the efficacy of treatment interventions, ultimately improving patient outcomes.

AB069. Type of personality and cancer-related pain in central nervous system (CNS) tumor patients: a cross-sectional study.

BACKGROUND: Pain is the most common complaint experienced by central nervous system (CNS) tumor patients. Pain, especially cancer pain, involves the whole aspect of a person, such as personality, cognition, and behavior. Personality characteristics play an important role in how a person perceives pain rate and deals with painful situation. This study aimed to describe types of personality and investigate relationship between types of personality and cancer-related pain in CNS patients. METHODS: This study was conducted at Cipto Mangunkusumo General Hospital from January to December 2023, that was determined by random sampling. The analysis included a total of 99 subjects from inpatient settings. In depth interview was used to assess type of personality and Numeric Rating Scale (NRS) was used to assess intensity of pain. Data analyses were carried out using the Chi-squared and Fisher's exact test to assess the relationship between types of personality and cancer-related pain in CNS patients. RESULTS: There were 99 subjects with mean age of 48.37±12.96 years, mostly women (60.6%). The results showed that in patients with CNS tumor, the most common neurological deficit was cancer pain (93.9%), consisting of no-mild pain (30.3%) and moderate-severe pain (69.7%). The prevalence of narcissistic personality was 73.7%, followed by histrionic personality 15.2%, and other personality (11.1%) such as borderline, obsessive-compulsive, and avoidant personality. Narcissistic personality traits were found in 48.5% of patients with moderate-severe pain. However, bivariate analysis showed that there was no significant relationship between types of personality and intensity of pain in CNS tumor patients (P=0.60). CONCLUSIONS: Although there was no significant relationship, cluster B personality (narcissistic, histrionic, and borderline) was found in a large percentage of CNS tumor patients. Research findings showed that intensity of pain was caused by biological components of pain and may be influenced by the patient's perception of pain itself, not solely due to personality. Therefore, it's important for health workers to pay attention and give optimal management to every patient's pain complaint, and not to ignore or minimize it. Psychiatrists can be involved by giving psychotherapy so that patients can deal with their pain in a more adaptive way.

AB068. Psychiatric disorder in central nervous system tumor patients and its related factors.

BACKGROUND: Patients of central nervous system (CNS) tumors have a potential to develop psychiatric disorder. These may present resulting from tumor mass, edema, or patient's failure to adapt to their illness and treatment. The presence of psychiatric disorders may cause disability, decreased daily functioning, reduced quality of life, and even death. In order to provide adequate treatment to patients with CNS tumors, it's important to evaluate the type of psychiatric disorder in patients with spinal and brain tumors. This study aimed to investigate the prevalence of psychiatric disorder dan related factors that exist in patients with brain and spinal tumors. METHODS: In a study conducted at Cipto Mangunkusumo General Hospital from January to December 2023, factors associated with psychiatric disorders in patients with CNS tumors were investigated. The analysis included a total of 161 subjects from inpatient settings. In depth interview was utilized to assess psychiatric disorder. Data analyses were carried out using the Chi-square and Fisher's exact test to assess the relationship between locations of tumor, neurological deficits, and psychiatric disorders. RESULTS: There were 161 subjects with mean age of 48.86±13.13 years, mostly women (59.0%). Patients with spinal tumor have more psychiatric disorders compared to their counterpart with intracranial tumor (79.1% and 76.3% respectively), while the most common psychiatric disorder was adjustment disorder. There is no significant relationship between tumor location and psychiatric disorder. In both patients with intracranial and spinal tumors, the most common neurological deficit was cancer pain (88.2%). However, bivariate analysis showed that among the neurological deficits found in the CNS tumor patients, dysphagia (P=0.02) and incontinence (P=0.02) have significant relationship with depression, while pain (P=0.02) and cognitive dysfunction (P=0.01) have significant relationship with adjustment disorder. It also showed that pain (P<0.001), cognitive dysfunction (P=0.002), and seizure (P=0.03) have significant relationship with organic mental disorder. CONCLUSIONS: Dysphagia, incontinence, pain, cognitive disfunction, and seizure were identified as risk factors for psychiatric disorders in intracranial and spinal tumor patients. The finding underscores the importance of screening and comprehensive psychiatric evaluations in patients with CNS tumors, as psychiatric symptoms may significantly impact their quality of life and treatment outcomes.

AB080. High-dose methotrexate with and without intra-thecal methotrexate and whole-brain radiotherapy for primary central nervous system lymphoma: a systematic review.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) requires effective & well-tolerated treatment strategies. The use of high-dose methotrexate (HD-MT) with or without intra-thecal methotrexate (IT-MT) and whole-brain radiotherapy (WBRT) has emerged as a prominent approach for PCNSL. This systematic review aims to assess the efficacy and safety of these treatment modalities. METHODS: A comprehensive search strategy identified relevant studies from PubMed, EMBASE, and Cochrane Library. The following search terms were used: "high-dose methotrexate", "primary central nervous system lymphoma", "intra-thecal methotrexate", and "whole-brain radiotherapy". We included randomized controlled trials (RCTs), cohort studies & case-controlled studies evaluating the use of HD-MT with or without IT-MT and whole-brain radiotherapy in the treatment of confirmed PCNSL. Data extraction & quality assessment was conducted by two independent reviewers. Primary outcomes include overall survival (OS), progression-free survival (PFS) & treatment-related adverse events (TRAEs). Secondary outcomes were neurological function and quality of life (QOL) assessments. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias Tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. RESULTS: We identified 5 studies, consisting of 1 RCT, 3 cohort studies, and 1 case-controlled study. Pooled analysis revealed that HD-MT with or without IT-MT and whole-brain radiotherapy significantly improved both OS and PFS compared to other treatment modalities but we found no significant difference between patients who received HD-MT with or without IT-MT. Combination therapy was generally well-tolerated, with manageable TRAE. Subgroup analyses stratified by age, disease stage, and other relevant factors demonstrated consistent efficacy and safety profiles across different patient populations. The risk of bias assessment indicated that the majority of the included studies had low-moderate risk of bias. CONCLUSIONS: There was no significant difference between patients who received HD-MT with or without IT-MT plus radiotherapy, emphasizing the comparable efficacy of these treatment modalities. Combination therapy was generally well-tolerated, with manageable TRAE. This highlights the favourable safety profile of HD-MT with fewer side effects compared with the combination of IT-MT.

Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients.

BACKGROUND: Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy. METHODS: Patients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle. RESULTS: Twenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell's syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively. CONCLUSION: Targeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing. TRIAL REGISTRATION: NCT04446962.