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Scholarly Works (230 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2017)

Background

Neuro-oncology caregivers face unique challenges. Caring for a patient who has a catastrophic, life-threatening diagnosis combined with progressive neurological decline can produce great distress. Experts agree that a formalized plan of care to address the needs of the neuro-oncology caregiver is needed.

Methods

In 2013, the Division of Neuro-Oncology at the University of California, San Francisco initiated a program designed to provide additional services to address the needs of the neuro-oncology caregiver. Records have been kept outlining program development, the caregivers seen, their identified needs, and services provided.

Results

From October 2013 through August 2015 staff met with 334 "new to clinic" caregivers, 90 of whom were caring for patients with newly diagnosed glioblastoma. One hundred ninety-eight caregivers were deemed at high risk for distress due to transitions in patient care that were occurring. One hundred forty-nine caregivers of former patients received bereavement services for up to 6 months. The areas of highest need were emotional support and advocacy issues. The number of caregiver needs increased as patients moved along the disease trajectory. The program was able to identify resources that were lacking. Dedicated staff allowed for improvement in the kinds of caregiver-specific support services offered.

Conclusion

Dedicated caregiver staff allows for developing relationships with caregivers across the disease trajectory and appears to be important in being able to offer individualized assessments and tailored care plans. Evaluation of caregiver and patient outcomes is the next step in understanding program effectiveness.
    Cover page: Creating a caregiver program in neuro-oncology
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2014)
    Medical therapies are an important part of adjunctive therapy for gliomas. In this chapter we will review the chemotherapeutic and targeted agents that have been evaluated in clinical trials in grade II-IV gliomas in the last decade. A number of randomized phase III trials were completed and reported. There has been a clear success in oligodendroglial tumors and low grade glioma. Although some progress has been made in glioblastoma, considerable work involving the multidisciplinary collaboration of basic science, translational and clinical investigators needs to be done to improve the outcome of patients with anaplastic astrocytoma and glioblastoma. In addition, tailoring treatment based on molecular cytogenetic characteristics is a major focus of research into precision based medicine for glioma.
      Cover page: Medical therapy of gliomas
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2018)
      Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) is a powerful non-invasive tool for characterizing spatial variations in metabolic profiles for patients with glioma. Metabolic parameters obtained using this technique have been shown to predict treatment response, disease progression, and transformation to a more malignant phenotype. The availability of ultra-high-field MR systems has the potential to improve the characterization of metabolites. The purpose of this study was to compare the metabolite profiles acquired with conventional long echo time (TE) MRSI at 3T with those obtained with short TE MRSI at 3T and 7T in patients with glioma. The data acquisition parameters were optimized separately for each echo time and field strength to obtain volumetric coverage within clinically feasible data acquisition times of 5-10 min. While a higher field strength did provide better detection of metabolites with overlapping peaks, spatial coverage was reduced and the use of inversion recovery to reduce lipid precluded the detection of lipid in regions of necrosis. For serial evaluation of large, heterogeneous lesions, the use of 3T short TE MRSI may thus be preferred. Despite the limited number of metabolites that it is able to detect, the use of 3T long TE MRSI gives the best contrast in choline/N-acetyl aspartate between normal appearing brain and tumor and also allows the separate detection of lactate and lipid. It may therefore be preferred for serial evaluation of patients with high-grade glioma and for detection of malignant transformation in patients with low-grade glioma.
        Cover page: Comparison between Short and Long Echo Time Magnetic Resonance Spectroscopic Imaging at 3T and 7T for Evaluating Brain Metabolites in Patients with Glioma
        • Multimedia
        • Peer Reviewed
        UC San Francisco Electronic Theses and Dissertations (2025)

        Gliomas are among the most common and aggressive primary brain tumors, with IDH-mutant and IDH-wildtype gliomas exhibiting distinct molecular and clinical characteristics. Despite advances in tumor classification and treatment strategies, prognostic uncertainty and therapeutic resistance remain major challenges in neuro-oncology. The present work investigates key genetic, molecular, and immune mechanisms that contribute to glioma progression and patient outcomes, with the goal of identifying novel biomarkers to improve risk stratification.

        To address these challenges, three complementary projects were conducted using genomic, transcriptomic, and immune profiling information.

        Transposable Elements in IDH-Wildtype Glioblastoma: Using RNA sequencing data from The Cancer Genome Atlas (TCGA), we analyzed the expression of transposable elements (TEs) in IDH-wildtype glioblastoma and their association with survival outcomes. Cox proportional hazards models and pathway enrichment analyses identified candidate TEs associated with reduced survival, proposing their role in genomic instability, and immune evasion.

        Molecular Evolution of IDH-Mutant Astrocytomas: Longitudinal genomic profiling of 205 tumor specimens from patients with IDH-mutant astrocytomas to assess acquired mutations driving tumor progression and treatment resistance. UCSF500 next-generation sequencing panel was used to identify RAS-MAPK pathway alterations (in KRAS, NRAS, BRAF, NF1, and LZTR1) that were enriched in high-grade recurrent tumors and correlated with inferior survival, highlighting their potential as molecular targets for therapy.

        Peripheral Immune Cell Dynamics in IDH-Mutant Gliomas After Surgical Resection: To investigate systemic immune changes in glioma patients, a longitudinal analysis of immune profiles of peripheral blood samples before and after surgery was conducted. Statistical modeling revealed shifts in circulating immune cell populations, particularly basophils and T-regulatory cells, that may reflect immune adaptations to tumor burden and surgical intervention.Collectively, these studies provide insights into glioma biology, identifying novel genetic drivers, prognostic biomarkers, and immune alterations that could inform personalized treatment strategies.

        By integrating molecular and immune profiling, this work contributes to the advancement of precision oncology approaches for glioma diagnosis, risk stratification, and proposes potentialtherapeutic targets.

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        • 3 supplemental ZIPs
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2021)
        BACKGROUND: Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. The aim of this study was to determine clinical practice patterns to acquire this information, interpret and utilize MT for patient care, and identify unmet needs in the practical clinical application of MT. METHODS: We conducted a voluntary online survey of providers within the Society for Neuro-Oncology (SNO) membership database between March and April 2019. RESULTS: We received 152 responses out of 2022 SNO members (7.5% of membership). 88.8% of respondents routinely order MT for newly diagnosed gliomas. Of those who do not, testing is preferentially performed in younger patients or those with midline tumors. 82.8% use MT in recurrent gliomas. Other common indications included: metastatic tumors, meningioma, and medulloblastoma. Many providers utilize more than one resource (36.0%), most frequently using in-house (41.8%) over commercially available panels. 78.1% used the results for clinical decision-making, with BRAF, EGFR, ALK, and H3K27 mutations most commonly directing treatment decisions. Approximately, half (48.5%) of respondents have molecular tumor boards at their institutions. Respondents would like to see SNO-endorsed guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials, and more educational programs on MT. CONCLUSION: This survey was marked by several limitations including response rate and interpretation of MT. Among respondents, there is routine use of MT in Neuro-Oncology, however, there remains a need for increased guidance for providers to effectively incorporate the expanding genomic data resulting from MT into daily Neuro-Oncology practice.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2017)
          Abstract

          PURPOSE

          7 Tesla (7T) MRI scanners can provide novel information to improve the characterization of gliomas. However, patients who receive 7T scans must undergo separate clinical evaluations at lower field strengths due to a lack of clinical validation of 7T anatomical imaging. The purpose of this study was to develop a robust volumetric anatomical imaging protocol for the clinical evaluation of patients with glioma at 7T and compare lesion definition to standard 3T imaging.

          METHODS

          3D T2-weighted, T2 FLAIR, and T1-weighted sequences at 7T were optimized to match the contrast, resolution, and scan time of corresponding clinical sequences at 3T. Ten patients with contrast-enhancing glioma (grades II-IV) were scanned with a protocol consisting of pre-contrast anatomical imaging and post-contrast T1-weighted imaging at both field strengths, with the 7T scan occurring in between the pre- and post-contrast 3T imaging. A half-dose of contrast was used at 7T, with an additional half-dose given immediately afterwards at 3T to provide similar lesion contrast given the 2.3-fold difference in field strength. Metrics for comparison between field strengths included volumes of T2 and contrast-enhancing lesions, and Likert-scale ratings (1-5) of lesion definition by a neuro-radiologist.

          RESULTS

          T2 and contrast-enhancing lesion volumes were not significantly different between field strengths, despite the trend in larger enhancing lesion volumes at 3T, which was expected given the protocol design. 7T T2-weighted and post-contrast T1-weighted images received on average half-point higher Likert-scale ratings than corresponding 3T images, whereas the opposite trend was observed with the T2 FLAIR and pre-contrast T1-weighted images.

          CONCLUSION

          Our pilot study suggests that clinical assessment of contrast-enhancing and T2-hyperintense lesions in glioma is feasible at 7T, which would obviate the need for two scans, allowing patients to take advantage of the increased sensitivity in metabolic and physiologic imaging available at 7T and ultimately improve patient care.
            Cover page: NIMG-64. THE POTENTIAL OF 7T ANATOMICAL IMAGING FOR CLINICAL ASSESSMENT OF CONTRAST-ENHANCING AND T2-HYPERINTENSE LESIONS IN PATIENTS WITH GLIOMA
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2013)
            Two major difficulties encountered in implementing Magnetic Resonance Spectroscopic Imaging (MRSI) in a clinical setting are limited coverage and difficulty in prescription. The goal of this project was to automate completely the process of 3D PRESS MRSI prescription, including placement of the selection box, saturation bands and shim volume, while maximizing the coverage of the brain. The automated prescription technique included acquisition of an anatomical MRI image, optimization of the oblique selection box parameters, optimization of the placement of outer-volume suppression saturation bands, and loading of the calculated parameters into a customized 3D MRSI pulse sequence. To validate the technique and compare its performance with existing protocols, 3D MRSI data were acquired from six exams from three healthy volunteers. To assess the performance of the automated 3D MRSI prescription for patients with brain tumors, the data were collected from 16 exams from 8 subjects with gliomas. This technique demonstrated robust coverage of the tumor, high consistency of prescription and very good data quality within the T2 lesion.
              Cover page: Automated prescription of oblique brain 3D magnetic resonance spectroscopic imaging.Creative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2018)
              Low-grade gliomas cause considerable morbidity and most will recur after initial therapy. At recurrence, low-grade gliomas can undergo transformation to high-grade gliomas (grade III or grade IV), which are associated with worse prognosis. Temozolomide (TMZ) provides survival benefit in patients with glioblastomas, but its value in patients with low-grade gliomas is less clear. A subset of TMZ-treated, isocitrate dehydrogenase‒mutant, low-grade astrocytomas recur as more malignant tumors with thousands of de novo, coding mutations bearing a signature of TMZ-induced hypermutation. Preliminary studies raise the hypothesis that TMZ-induced hypermutation may contribute to malignant transformation, although with highly variable latency. On the other hand, hypermutated gliomas have radically altered genomes that present new opportunities for therapeutic intervention. In light of these findings and the immunotherapy clinical trials they inspired, how do patients and providers approach the risks and benefits of TMZ therapy? This review discusses what is known about the mechanisms and consequences of TMZ-induced hypermutation and outstanding questions regarding its clinical significance.
                Cover page: Temozolomide-associated hypermutation in gliomas
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2013)
                Two major difficulties encountered in implementing Magnetic Resonance Spectroscopic Imaging (MRSI) in a clinical setting are limited coverage and difficulty in prescription. The goal of this project was to automate completely the process of 3D PRESS MRSI prescription, including placement of the selection box, saturation bands and shim volume, while maximizing the coverage of the brain. The automated prescription technique included acquisition of an anatomical MRI image, optimization of the oblique selection box parameters, optimization of the placement of outer-volume suppression saturation bands, and loading of the calculated parameters into a customized 3D MRSI pulse sequence. To validate the technique and compare its performance with existing protocols, 3D MRSI data were acquired from six exams from three healthy volunteers. To assess the performance of the automated 3D MRSI prescription for patients with brain tumors, the data were collected from 16 exams from 8 subjects with gliomas. This technique demonstrated robust coverage of the tumor, high consistency of prescription and very good data quality within the T2 lesion.
                  Cover page: Automated prescription of oblique brain 3D magnetic resonance spectroscopic imaging
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2017)
                  The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classification, which is now for adult diffuse glioma centered around isocitrate dehydrogenase (IDH) and 1p/19q diagnostics. This revised classification is reviewed with a focus on adult brain tumors, and includes a recommendation of genes of which routine testing is clinically useful. Apart from assessment of IDH mutational status including sequencing of R132H-immunohistochemistry negative cases and testing for 1p/19q, several other markers can be considered for routine testing, including assessment of copy number alterations of chromosome 7 and 10 and of TERT promoter, BRAF, and H3F3A mutations. For glioblastoma, IDH mutated the term astrocytoma grade IV could be considered. It should be considered to treat IDH wild-type grades II and III diffuse glioma with polysomy of chromosome 7 and loss of 10q as glioblastoma. New developments must be more quickly translated into further revised diagnostic categories. Quality control and rapid integration of molecular findings into the final diagnosis and the communication of the final diagnosis to clinicians require systematic attention.
                    Cover page: A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics.
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