Monitoring Patients with IDH-Mutant Astrocytoma Using Dynamic and Steady-State Metabolic Imaging
Abstract
Gliomas are the most common malignant primary brain tumors in adults. Patients with mutations in isocitrate dehydrogenase (IDH), commonly at the ages of between 20 and 40 years old, have longer survival compared to those who do not have mutations. The first line treatment is maximal safe resection. If the patient has a grade 2 lesion, further treatment may be delayed until they progress. Standard of care (SOC) treatment for recurrent, previously untreated grade 2 and for newly diagnosed grade 3 IDH mutant astrocytoma include radiation therapy and temozolomide. Although patients do benefit from these treatments, variation between individuals still exists. Most patients eventually progress, and the majority experience malignant transformation to a higher grade. Cancer vaccines are considered to be a safe and effective option for this population, because they have slower tumor growth rate and are generally not immune-compromised. However, inflammatory responses to the vaccines makes it difficult to assess treatment efficacy. These limitations have led to the consideration of novel approaches that can improve the characterization of tumor burden for treatment planning, assessment of malignant progression, and differentiation of progression from treatment effects. Proton MR spectroscopy, also called proton MR metabolic imaging, is a method that can provide the concentrations of in vivo (steady state) brain metabolites non-invasively, which has been implemented into our clinical examinations for patient evaluation. Hyperpolarized carbon-13 pyruvate MR metabolite imaging is another promising new technology that provides real-time (dynamic) brain metabolism. After the injection of carbon-13 pyruvate, which is non-radioactive, it converts to lactate and bicarbonate in the brain within a short time. The preclinical work suggests that it could provide an early biomarker of response to therapy. First-in-human brain of hyperpolarized carbon-13 pyruvate were reported recently for its safety and feasibly. In the proposed study, we will investigate patients with IDH mutant astrocytoma by combining these two metabolic imaging methods. We will first evaluate the metabolic changes when receiving SOC treatment (Aim 1) to understand the metabolic changes during the treatment, and then we will establish metabolic signatures that are associated with malignant progression to a higher grade, recurrent tumor (the same grade as the initial diagnosis), and treatment related effects in patients who receive SOC treatment (Aim 2), or immunotherapy trial (Aim 3). We hypothesize that the combination of steady state (proton) and dynamic (carbon-13) metabolic imaging will improve our understanding of the biologic processes during treatment, which will aid neuro-oncologists in making timely decisions on how to manage their patients. The proposed study will address The Fiscal Year 2020 Peer Reviewed Cancer Research Program Military Health Focus Areas on “brain cancer,” “immunotherapy,” and “early detection/diagnosis, prognosis, treatment, and/or survivorship that may impact mission readiness and the health and well-being of military members, Veterans, their beneficiaries, and the general public.” Upon completion of the proposed study, we will have created metabolic signatures that can assess SOC treatment-induced changes that are associated with malignant transformation and that can differentiate tumor progression from treatment effects. These metabolic metrics can be used for treatment planning, for identifying responders and early markers of failure, for directing tissue sampling to the most malignant regions, and for assessing response to treatment. We will also obtain metabolic information associated with IDH mutation, how they change during the course of the disease and with treatment. Thus, these results will direct the selection of appropriate patients for enrolling into precision medicine-based clinical trials. Successful completion of the study w
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110412
Entities
People
- Yan Li
Organizations
- United States Army
- University of California, San Francisco