Consolidation Regimen and Cerebral Atrophy in Patients with Primary Central Nervous System Lymphoma.

Background: In primary central nervous system lymphoma (PCNSL), the extent to which post-methotrexate consolidation contributes to neurotoxicity is unclear. Concerns for neurotoxicity from standard-dose whole-brain radiotherapy (WBRT) have led to declining use. Cerebral atrophy is an established surrogate for neurotoxicity; however, the relative extent to which modern consolidation (i.

A Phase II Study Assessing Long-term Response to Ibrutinib Monotherapy in Recurrent or Refractory CNS Lymphoma.

Purpose: Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase. We previously reported the safety and short-term antitumor activity of ibrutinib in 20 patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL).

Patients And Methods: We enrolled 26 additional patients with r/r PCNSL/SCNSL into the dose-expansion cohort of the trial into a combined cohort of 46 patients (31 with PCNSL and 15 with SCNSL).

State of the Art in Low-Grade Glioma Management: Insights From Isocitrate Dehydrogenase and Beyond.

Low-grade gliomas present a formidable challenge in neuro-oncology because of the challenges imposed by the blood-brain barrier, predilection for the young adult population, and propensity for recurrence. In the past two decades, the systematic examination of genomic alterations in adults and children with primary brain tumors has uncovered profound new insights into the pathogenesis of these tumors, resulting in more accurate tumor classification and prognostication. It also identified several common recurrent genomic alterations that now define specific brain tumor subtypes and have provided a new opportunity for molecularly targeted therapeutic intervention.

Bruton's tyrosine kinase (BTK) inhibitors for the treatment of primary central nervous system lymphoma (PCNSL): current progress and latest advances.

The incidence of primary central nervous system lymphoma (PCNSL) has steadily increased, particularly in elderly patients. Although highly responsive to first-line chemotherapy and radiotherapy, approximately 50% of patients relapse or become refractory within 1 year. Prognosis following relapse is dismal and no standard salvage therapy exists.

Central Nervous System Lymphoma.

Objective: This article reviews the clinical presentation, diagnostic workup, staging, and treatment of primary central nervous system (CNS) lymphoma and common manifestations of secondary CNS lymphoma.

Latest Developments: Lymphoma can arise in the CNS de novo (primary CNS lymphoma) or as the result of systemic disease (secondary CNS lymphoma). Symptoms may include focal neurologic deficits related to the disease site, cognitive decline, and symptoms of increased intracranial pressure.

Long-term Outcomes in Primary CNS Lymphoma After R-MVP and High-Dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplant.

Background And Objectives: Primary CNS lymphoma (PCNSL), a rare CNS malignancy, is usually treated with high-dose methotrexate in the first-line setting, typically followed by consolidation therapy. Due to the broad range of currently available treatments for PCNSL, comparability in long-term follow-up studies is limited, and data are scattered across small studies.

Methods: In this study, we report the long-term survival of patients with newly diagnosed immunocompetent PCNSL, enrolled in a phase II trial from June 2005 to September 2011.

Preclinical and clinical evaluation of Buparlisib (BKM120) in recurrent/refractory Central Nervous System Lymphoma.

Central Nervous System (CNS) Lymphomas are aggressive brain tumors with limited treatment options. Targeting the phosphoinositide 3-kinase (PI3K) pathway yields promising responses across B-cell malignancies, but its therapeutic potential in CNS lymphomas remains unexplored. We present pre-clinical and clinical data on the pan-PI3K inhibitor Buparlisib in CNS lymphomas.

Is more better? Increased doses of high dose methotrexate and addition of rituximab is associated with improved outcomes in a large primary CNS lymphoma cohort.

Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive primary brain tumor. While high dose methotrexate (HDMTX) regimens remain standard of care, it remains unclear if optimization of HDMTX doses and the addition of rituximab provide clinical benefit. Over the last 30 years, standard care given at Memorial Sloan Kettering Cancer Center (MSKCC) has evolved, allowing the comparison of patients receiving different numbers of HDMTX doses and those treated with and without rituximab.

Glioblastoma and Other Primary Brain Malignancies in Adults: A Review.

Importance: Malignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%.

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series.

Background And Objectives: To report the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma.

Methods: Single-center retrospective series of patients with glioma treated with olaparib/TMZ from September 2018 to December 2021.

Results: Twenty patients (median age: 42 years, median Karnofsky Performance Status: 90) received olaparib/TMZ for diagnoses of -mutant oligodendroglioma (n = 5), mutant astrocytoma grade 2-3 (n = 4), -mutant astrocytoma grade 4 (n = 7), or wildtype glioma (n = 4).

Routine use of low-dose glucarpidase following high-dose methotrexate in adult patients with CNS lymphoma: an open-label, multi-center phase I study.

Background: High-dose methotrexate (HD-MTX) has broad use in the treatment of central nervous system (CNS) malignancies but confers significant toxicity without inpatient hydration and monitoring. Glucarpidase is a bacterial recombinant enzyme dosed at 50 units (u)/kg, resulting in rapid systemic MTX clearance. The aim of this study was to demonstrate feasibility of low-dose glucarpidase to facilitate MTX clearance in patients with CNS lymphoma (CNSL).

Update on Novel Therapeutics for Primary CNS Lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma isolated to the central nervous system or vitreoretinal space. Standard treatment consists of cytotoxic methotrexate-based chemotherapy, with or without radiation. Despite high rates of response, relapse is common, highlighting the need for novel therapeutic approaches.

Primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or vitreoretinal space, without evidence of systemic involvement. The diagnosis of PCNSL requires a high level of suspicion because clinical presentation varies depending upon involved structures. Initiation of treatment is time sensitive for optimal neurologic recovery and disease control.

DNA Repair Mechanisms and Therapeutic Targets in Glioma.

Purpose Of Review: This review discusses current and investigative strategies for targeting DNA repair in the management of glioma.

Recent Findings: Recent strategies in glioma treatment rely on the production of overwhelming DNA damage and inhibition of repair mechanisms, resulting in lethal cytotoxicity. Many strategies are effective in preclinical glioma models while clinical feasibility remains under investigation.

Prognostic value of [F]FDG PET/CT in patients with CNS lymphoma receiving ibrutinib-based therapies.

Purpose: Current clinical and imaging tools remain suboptimal for predicting treatment response and prognosis in CNS lymphomas. We investigated the prognostic value of baseline [F]FDG PET in patients with CNS lymphoma receiving ibrutinib-based treatments.

Methods: Fifty-three patients enrolled in a prospective clinical trial and underwent brain PET before receiving single-agent ibrutinib or ibrutinib in combination with methotrexate with or without rituximab.

Primary central nervous system lymphoma: a narrative review of ongoing clinical trials and goals for future studies.

Primary central nervous system lymphoma (PCNSL) is a rare disease of the brain, spine, cerebrospinal fluid (CSF) and/or vitreoretinal space. PCNSL is chemo and radiosensitive but relapse is common even years after initial treatment. Outside of consensus regarding the use of high-dose methotrexate (HD-MTX) for first line treatment, there is little uniformity in the management of newly diagnosed or relapsed PCNSL.

Clinical trial of proton craniospinal irradiation for leptomeningeal metastases.

Background: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors.

Central Nervous System Lymphoma: Approach to Diagnosis and Treatment.

Central nervous system lymphoma (CNSL) is a rare form of extranodal non-Hodgkin lymphoma. Central nervous system lymphoma can be primary (isolated to the central nervous space) or secondary in the setting of systemic disease. Treatment of CNSL has improved since the introduction of high-dose methotrexate and aggressive consolidation regimens.

Prognostic and radiographic correlates of a prospectively collected molecularly profiled cohort of IDH1/2-wildtype astrocytomas.

Background: In the molecular era, the relevance of tumor grade for prognostication of IDH1/2-wildtype (WT) gliomas has been debated. It has been suggested that histologic grade II and III astrocytomas with molecular features of glioblastoma, IDH1/2-WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials.

Methods: We integrated prospective clinical sequencing from 564 patients with IDH1/2-WT gliomas (26 grade II, 71 grade III and 467 grade IV) with clinical and radiographic data to assess associations between molecular features, grade and outcome.

Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival.

Purpose: Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation and EGFR amplification are markers that may play a role in prognostication, treatment, and/or clinical trial eligibility. Quantification of MGMT and EGFR protein expression may offer an alternative strategy towards understanding GBM.