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).

Ischemic Stroke with Comorbid Cancer Has Specific miRNA-mRNA Networks in Blood That Vary by Ischemic Stroke Mechanism.

Objective: Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer.

Methods: We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30).

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.

Characterization of Mucosal-Associated Invariant T Cells in Oral Lichen Planus.

Oral lichen planus (OLP) is an inflammatory condition of unknown cause that has been associated with concurrent candidal infection. Mucosal-associated invariant T (MAIT) cells express the T cell receptor TCRVα7.2 and are activated by riboflavin intermediates produced by microbes.

Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis.

Purpose: Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT.

Patients And Methods: We conducted a randomized, phase II trial of pCSI versus IFRT in patients with non-small-cell lung cancer and breast cancers with LM.

Ischemic stroke with cancer: Hematologic and embolic biomarkers and clinical outcomes.

Background: Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death.

Objectives: To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes.

Methods: We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020.

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).

Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study.

Objective: The objective of this study was to examine the pathophysiology of ischemic stroke with cancer.

Methods: We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each.

Experiences in Electronic Consultation (eConsult) Service in Gynecology from a Quaternary Academic Medical Center.

To evaluate an academic institution's implementation of a gynecologic electronic consultation (eConsult) service, including the most common queries, turnaround time, need for conversion to in-person visits, and to demonstrate how eConsults can improve access and convenience for patients and providers. This is a descriptive and retrospective electronic chart review. We obtained data from the UCSF eConsult and Smart Referral program manager.

Lack of survival advantage among re-resected elderly glioblastoma patients: a SEER-Medicare study.

Background: The survival benefit of re-resection for glioblastoma (GBM) remains controversial, owing to the immortal time bias inadequately considered in many studies where re-resection was treated as a fixed, rather than a time-dependent factor. Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we assessed treatment patterns for older adults and evaluated the association between re-resection and overall survival (OS), accounting for the timing of re-resection.

Methods: This retrospective cohort study included elderly patients (age ≥66) in the SEER-Medicare linked database diagnosed with GBM between 2006 and 2015 who underwent initial resection.

Cancer and Embolic Stroke of Undetermined Source.

One-quarter to one-third of ischemic strokes have no established mechanism after standard diagnostic evaluation and are classified as embolic stroke of undetermined source (ESUS). Failure of randomized trials to demonstrate a benefit of direct oral anticoagulants over aspirin for the treatment of ESUS as a single homogeneous entity has led to renewed interest by stroke experts to divide ESUS into subgroups. Emerging data suggest that active cancer, which is present in 5% to 10% of patients with ESUS, is a distinct and important subgroup of ESUS with unique clinical characteristics, underlying pathophysiologies, and treatment and prognostic considerations.

Biochemical Pathways and Modeling.

The precise etiology of the biochemical changes and the resulting constellation of symptoms seen in polycystic ovary syndrome (PCOS) has remained a mystery. Despite advances in our knowledge, the pathogenesis and alterations in the biochemical pathways underlying this disease are still not fully understood. PCOS is a multifactorial syndrome where a combination of genetics, lifestyle, and hormone abnormalities all play an intertwining role.

Phase I/II study of sorafenib in combination with erlotinib for recurrent glioblastoma as part of a 3-arm sequential accrual clinical trial: NABTC 05-02.

Background: Receptor tyrosine kinases such as epidermal growth factor receptors (EGFRs) and their downstream signaling pathways such as the Ras-Raf-mitogen-activated protein kinase (MAPK) pathway play important roles in glioblastoma (GBM). This study investigated the safety, pharmacokinetics, and efficacy of sorafenib (Ras/Raf/MAPK inhibitor) in combination with erlotinib (EGFR inhibitor) for treatment of recurrent GBMs.

Methods: Patients with recurrent GBM were eligible.

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.

Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer.

Purpose: The CellSearch® system has been used to identify circulating tumor cells (CTCs) in cerebrospinal fluid (CSF) to diagnose leptomeningeal metastasis (LM) in patients with epithelial cancers. Using this system, we prospectively explored sequential CSF CTC enumeration in patients with LM from HER2+ cancers receiving intrathecal (IT) trastuzumab to capture dynamic changes in CSF CTC enumeration.

Methods: CSF from patients enrolled in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was obtained on day 1 of each cycle and was evaluated by the CellSearch® platform for CTC enumeration.

Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma.

Purpose: Malignant glioma (MG) is the most deadly primary brain cancer. Signaling though the PI3K/AKT/mTOR axis is activated in most MGs and therefore a potential therapeutic target. The mTOR inhibitor temsirolimus and the AKT inhibitor perifosine are each well-tolerated as single agents but with limited activity reclinical data demonstrate synergistic anti-tumor effects from combined treatment.

The risk of arterial thromboembolic events after cancer diagnosis.

Background: Retrospective studies have reported an association between cancer and arterial thromboembolic event (ATE) risk.

Objectives: We sought to confirm this in a prospective cohort with adjudicated outcomes.

Methods: We evaluated participants enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study with Medicare coverage for 365 days before their baseline visit (2003-2007).

Comparison of Radiographic Approaches to Assess Treatment Response in Pituitary Adenomas: Is RECIST or RANO Good Enough?

Context: Pituitary adenomas (PA) are often irregularly shaped, particularly posttreatment. There are no standardized radiographic criteria for assessing treatment response, substantially complicating interpretation of prospective outcome data. Existing imaging frameworks for intracranial tumors assume perfectly spherical targets and may be suboptimal.

Cancer-Related Ischemic Stroke Has a Distinct Blood mRNA Expression Profile.

Background and Purpose- Comorbid cancer is common in patients with acute ischemic stroke (AIS). As blood mRNA profiles can distinguish AIS mechanisms, we hypothesized that cancer-related AIS would have a distinctive gene expression profile. Methods- We evaluated 4 groups of 10 subjects prospectively enrolled at 3 centers from 2009 to 2018.