Schwannoma

BACKGROUND AND RATIONALE 6-\[18F\]fluoro-dihydroxyphenylalanine (18F-DOPA) is a large neutral amino acid that resembles natural L-3.4-dihydroxyphenylalanine (L-DOPA) biochemically. L-DOPA is a precursor for dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline), collectively known as catecholamines. 18F-DOPA enters the biochemical pathway of L-DOPA both in the brain and peripherally, and can be imaged with a positron emission tomography / computed tomography (PET/CT) scanner. 18F-DOPA can therefore allow imaging of the L-DOPA metabolic pathway with a high target-to-background ratio providing valuable information for a number of diseases. While 18F-DOPA is an established diagnostic tracer at a number of different institutions globally, given the short half-life of 18F (110 minutes) this tracer cannot be imported for local use. The Edmonton PET Centre has recently developed a production method for this tracer allowing local access. An initial study at the University of Alberta (Pro00055342) has demonstrated this tracer to have an acceptable safety profile, an expected biodistribution (both physiologic and disease-related), and has established clinical efficacy of the tracer. In March, 2020 the University of Alberta Hospital (UAH) installed a new PET/CT scanner (GE Discovery MI) with a digital detector system and new iterative image reconstruction algorithms that represent a substantial technological improvement compared to the previously installed scanner. It is expected that this new system will reduce artifact and will increase the sensitivity for the detection of smaller lesions. Our initial study demonstrated rapid urinary excretion with intense collection of activity within the urinary bladder. While this physiology was expected, it did result in diminished image quality in the evaluation of the pelvis in some patients. Improved image reconstruction algorithms available on the new GE Discovery MI PET/CT system may improve imaged quality related to this problem. Based on our experience with 18F-fluorodeoxyglucose (FDG) PET/CT scans, the administration of intravenous furosemide prior to imaging can also substantially improve the image quality in the pelvis. These potential improvements have not yet been established with 18F-DOPA. A second observation from our initial study was that many participants demonstrated intense early activity at the gallbladder fundus. While biliary and gallbladder activity are described in the normal biodistribution of 18F-DOPA, the observed distribution suggests that the gallbladder fundus activity reflects primary uptake rather than reflux of activity within bile into the gallbladder. The rationale for this study is to explore the efficacy of these optimization parameters (new digital PET/CT camera system and use of intravenous furosemide) in the context of 18F-DOPA PET/CT imaging for patients with clinical indications for the scan. Imaging data from this study will be compared with data from the prior study (Pro00055342) to determine if the new digital detector PET/CT technology and preparatory furosemide administration improves image quality for these patients. A subgroup will also be scanned dynamically at the abdomen to better assess the pattern of gallbladder activity over time. This will include a mixture of clinical indications listed within the inclusion criteria. All patients will be screened for a history of previous gallbladder disease at the time of the scan by questionnaire. The intention of this sub-study is to better determine 18F-DOPA activity patterns associated with the gallbladder and to explore if there is a correlation between dopaminergic degeneration in the brain and the gallbladder. PURPOSE AND STUDY OBJECTIVE: Trial Type: Phase III non-randomized, non-blinded prospective cohort clinical trial of patients with a clinical indication for 18F-DOPA PET/CT imaging. The primary purpose of this study is to assess optimization parameters for 18F-DOPA PET CT imaging at UAH including the impact of new digital detector PET/CT technology as well as the impact of preparatory intravenous furosemide administration on image quality within the pelvis. A secondary purpose of this study is to better delineate the pattern of 18F-DOPA activity associated with the gallbladder and to explore if there is a relationship between dopaminergic denervation in the gallbladder and the brain. Only patient populations for which there are established clinical indications for the use of 18F-DOPA will be included in this study. Participation in this study will allow access to this tracer for patients in Alberta as there is no Health Canada approved similar tracer currently available. 18F-DOPA is an established clinical tracer at multiple institutions globally and has been approved for clinical use at multiple European centres for many (10+) years. Established clinical indications in the literature include: 1. Pediatric patients (less than 18 years old) with congenital hyperinsulinism. The 18F-DOPA scan is used to plan required surgical intervention for these patients. 2. Pediatric patients (less than 18 years old) with neuroblastoma. The 18F-DOPA scan is indicated for pre-operative assessment of a mass suspected to be a neuroblastoma, staging, re-staging, and assessment of recurrence in this patient group. 3. Pediatric (less than 18 years old) or Adult patients (18 or older) with known or clinically suspected neuroendocrine tumor. These include patients with carcinoid tumor, pheochromocytoma, paraganglioma, and medullary thyroid cancer. 18F-DOPA is indicated for metabolic assessment of a mass suspected to represent one of these tumor-types, for staging of a known tumor, for re-staging, and for assessment of recurrence in this patient group. 4. Adult patients (18 or older) with a clinical suspicion of Parkinson's disease or Lewy body dementia. 18F-DOPA is indicated to differentiate benign essential tremor from Parkinson's disease in this patient group \[22-26\]. 18F-DOPA may also be used to differentiate Lewy body dementia from other dementia types. 5. Pediatric (less than 18 years old) or Adult patients (18 or older) with brain tumors (primary or metastatic). 18F-DOPA is indicated for biopsy planning, radiation therapy planning, and post-therapy assessment to differentiate residual viable tumor from post-therapy necrosis in this patient population. When requested for patients falling into one of these diagnostic groups, an 18F-DOPA PET/CT scan will be performed and interpreted clinically with the results conveyed to the referring physician. Image optimization (the primary study objective) will be evaluated based on the following: * For patients with abnormal activity, the smallest 3 lesions will be recorded in terms of size (mm) and activity (SUVmax). For PET-avid lesions, the size measurement will be based on measuring the maximum dimension of the corresponding lesion on the CT scan component if possible. If not possible, a size measurement based on the PET images will be used. The minimum lesion size and average (3 smallest lesions) will be compared with a cohort of scans acquired on the previous non-digital PET/CT scanner (retrospective cohort of 50 positive patients, Pro00055342). * The SUVmax, SUVmean, and SUV standard deviation of urinary bladder activity will be measured and compared to a retrospective cohort of 50 patients from a previous study (Pro00055342) * A subjective score will be applied to the pelvis with respect to image artifact related to bladder activity (0 = no artifact, 1 = mild artifact, 2 = severe artifact). This will be compared to scoring of the previous study (retrospective cohort of 50 patients, Pro00055342) retrospectively. Gallbladder activity pattern (the secondary objective) will be evaluated based on the following: * SUVmax measurements of the gallbladder fundus, gallbladder neck, common bile duct, right and left main intrahepatic ducts, and liver parenchyma (right and left lobes, 3 cm diameter VOI) will be measured at 5 minute increments. These will be analyzed in total, and subgroups will be compared (32 PD vs. 32 non-PD participants). * All participants will be screened by questionnaire at the time of the scan as to whether there is a history of previous gallbladder disease. The positive response rate will be compared between three groups: non-PD patients, PD patients with objective evidence of dopaminergic denervation (positive FDOPA scan), PD patients without objective evidence of dopaminergic denervation (negative FDOPA scan). PATIENT POPULATION: A total of 800 patients who meet the inclusion criteria will be identified based on referrals from physicians who deem the imaging studies potentially useful for clinical care. It is anticipated that complete enrollment will take 5 years (approximately 160 scans per year). Sample size calculation is based on the following. There will typically be 5 participants total scanned per day. Dynamic imaging will be restricted to one patient per scanning day due to time constraints related to the scanner, as this requires the participant to lie quietly in the PET/CT scanner for up to one hour. Allowing for this restriction, it is estimated that the overall participation rate for dynamic scanning will be 10%. Based on a minimum total sample size of 64 participants for the secondary objective analysis, a total minimum study population of 640 is required. Allowing for some potential buffer for recruitment, a total of 800 participants is planned. The minimum sample size of 64 participants is based on the following estimations: gallbladder fundus SUVmax mean 10.9, SUVmax DS 4.6 (measured from cohort of 10 patients from the previous study), α = 0.05, and power = 0.80. Two groups of 32 participants (64 total) should allow for detection of a minimum 30% difference in SUVmax involving the gallbladder fundus between the two groups.

Prior to the onset of this study, the utility of Ga-68-DOTATATE PET/MRI in meningioma had not been explored. The investigator's pilot study serving as the basis for the proposed protocol resulted in the - to the investigators' knowledge - largest case series of 21 patients in whom Ga-68 DOTATATE PET/MRI demonstrated utility in the assessment of meningioma, including assessment for postsurgical/postradiation recurrence, detection of additional lesions not visualized on MRI alone, and evaluation of osseous invasion. Based on this initial experience, investigators continued to study the impact of Ga-68-DOTATATE PET/MRI in the assessment of the extent of residual tumor in patients status post meningioma resection, specifically in patients in whom tumor location limits resectability, patients with WHO grade II/III disease, and patients with history of SRS who develop postradiation change.

Conventional 18F-FDG PET/CT has important diagnostic value in cell metabolism level, early metastasis, judging malignant potential and prognosis of tumors. It has been routinely used for staging and restaging of most tumors, but there are still some tumors with low uptake of 18F-FDG PET/CT. Receptor imaging with a single target also has some limitations in clinical application. For example, not all diseased cells express a large amount of single receptor on the surface, which greatly affects the judgment of the nature of the lesion. The dual-target molecular imaging based on GRPr expressed in the lesion site and integrin αvβ3 receptor highly expressed on the surface of the lesion neovascularization will overcome the above limitations and make full use of the advantages of the dual-target molecular imaging, which will greatly assist the diagnosis of malignant tumors such as breast\\brain\\prostate tumor which have high GRPr and αvβ3 receptor expression . In this study, a novel dual-target imaging agent 68Ga-RM26-RGD was used for PET/CT imaging of breast\\brain\\prostate cancer, compared with conventional 18F-FDG, or single target imaging agent 68Ga-RGD or 68Ga-RM26 PET/CT imaging.

Bevacizumab can be an effective treatment for individuals with NF2 and improve different nerve functions (like hearing, tinnitus or balance problems) and the quality of life of NF2 patients. However, bevacizumab is not effective in all patients or all tumors, at the cost of moderate toxicity and considerable financial burden. Therefore, this observational study will validate an imaging biomarker method to predict bevacizumab efficacy in order to avoid adverse effects and high costs in non-responders to bevacizumab treatment. Patients will undergo standard-of-care treatment with the sole addition of a pre-treatment 89Zr-Bevacizumab PET/CT-scan. Per standard-of-care bevacizumab therapy is administered every three weeks for six months. To monitor treatment effect, follow-up is performed at 3-month intervals.

Primary Objectives: To validate resting-state fMRI (rs-fMRI) mapping of language and motor (hand and tongue) areas obtained by using the software developed in this research: We will test the non-inferiority of rs-fMRI comparing to task-based fMRI (tb-fMRI) by using intra-operative direct cortical stimulation as the gold standard. To test whether CVR mapping using the software developed in this research will increase confidence of fMRI mapping of language and motor (hand and tongue) areas: We will test whether the accuracy of fMRI, assessed by using intra-operative direct cortical stimulation as the gold standard, will improve after incorporating the CVR mapping. Secondary Objectives: To optimize the rs-fMRI and CVR mapping software during the development phases and to test feasibility of the post-processing workflow using clinical images.

The glioblastoma microenvironment is well known to be immunosuppressive. One mechanism of immunosuppression involves systemic and local accumulation of myeloid-derived suppressor cells (MDSCs) that inhibit cytotoxic immune cell populations and contribute to immune suppression. Glioblastoma(GBM) patients have increased circulating MDSCs compared to lower grade glioma patients, and GBM patients with a better prognosis have reduced MDSCs in their tumors as well as in their peripheral circulation. A trial (NCT02669173) performed at the Cleveland Clinic demonstrated that pre-surgical anti-MDSC therapy (capecitabine) was associated with reduced circulating MDSCs and increased cytotoxic immune infiltration in tumor tissue. This proof-of-principle pilot study demonstrated that targeting MDSCs in patients can attenuate tumor-induced immunosuppression. Subsequent work at the Cleveland Clinic demonstrated that MDSCs relied on dipeptidyl peptidase 4 (DPP-4) for entry into the brain and overall MDSC function. Screening for a DPP-4 inhibitor identified sitagliptin as a good inhibitor that has limited toxicity with efficacy in pre-clinical models. Investigators hypothesize that treating GBM patients with sitagliptin will deplete circulating MDSCs and reduce their entry into the brain, reversing systemic and intratumoral immunosuppression. To test this hypothesis, investigators plan a "window of opportunity" clinical trial to evaluate the safety and biological impact of sitagliptin treatment in patients with recurrent grade 4 glioma undergoing clinically indicated surgical resection. For this trial, investigators will enroll 48 patients; 36 will undergo presurgical treatment with sitagliptin and 12 with no presurgical treatment. All patients will receive post-operative sitagliptin and chemotherapy until disease progression.

Background: * Zotiraciclib is a multi-kinase inhibitor that has been shown to have anti-glioma effects through transcriptional suppression, mitochondrial dysfunction, and adenosine 5'-triphosphate (ATP) reduction in glioblastoma in our preclinical studies * Zotiraciclib is orally administered and likely penetrates the blood brain barrier (BBB). There has been a clinical experience in using zotiraciclib as a single agent and in combination with other chemotherapy agents in cancers, including malignant gliomas * Our phase I study of zotiraciclib and temozolomide (TMZ) in recurrent high-grade astrocytomas determined the maximum tolerated dose (MTD) of zotiraciclib in combination with TMZ and demonstrated the safety of the treatment in recurrent high-grade glioma patients * Preliminary efficacy analysis of Phase I demonstrated an improved response to zotiraciclib in combination with TMZ in IDH-mutant gliomas compared to the IDH-wildtype counterpart * A selective vulnerability to zotiraciclib as a single agent was demonstrated in the preclinical models of IDH-mutant gliomas Objectives: * Phase I: To estimate recommended phase II dose (RP2D) of zotiraciclib * Phase II: To determine 12-months progression free survival (PFS) in participants with recurrent glioma, IDH1/2-mutant, World Health Organization (WHO) grade 3 treated with zotiraciclib in comparison with the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors Eligibility: * Age \>=15; Karnofsky performance status (KPS) \>=70% * Histological confirmation of diffuse glioma, WHO grades 2-4 with IDH1/2 mutation status confirmed by DNA sequencing * Have recurrent disease * Have prior treatment of radiation and/or conventional chemotherapies * No prior use of bevacizumab as a treatment for a brain tumor Design: * This is a phase I/II study to evaluate the safety and efficacy of zotiraciclib as a single agent in recurrent IDH-mutant gliomas. * Initially, 9-24 participants (Cohort 1) will be assigned to Phase I to estimate recommended phase 2 dose (RP2D) of zotiraciclib. * Once RP2D is estimated, we will start enrollment into cohorts for Phase II, non-surgical participants (Cohorts 2-4), and surgical (Cohort 5). This trial plans to enroll up 64 evaluable participants. * Drug will be administered on days 1, 4, 8, 11, 15, 18 in cycles of 28 days for a maximum of 18 cycles. Starting dose is 200 mg. In the case that 200 mg is not tolerable, a lower dose 150 mg, will be evaluated. If 200 mg is tolerated well, a higher dose level will be evaluated at 250 mg. * Participants in the surgical cohort will get an additional single pre-treatment with one dose of study drug at the RP2D on Day 1 of Cycle 0, followed by brain tumor biopsy or surgical resection within 24 hours on Day 2 of Cycle 0. Approximately 2-4 weeks after surgery or biopsy participants in this Cohort will continue treatment with the study drug and start Day 1 of Cycle 1.

The study aims to compare the efficacy of combining Bevacizumab with NaviFUS System relative to Bevacizumab alone in patients with rGBM who have previously undergone radiotherapy and temozolomide chemotherapy. Any patient with a histological diagnosis of GBM who meets all of the specific eligibility criteria may participate in this study by signing informed consent in person or through their legal representative. Eligible patients will undergo a 2-week baseline observation screening period. Up to 32 evaluable patients will be recruited in this study. Eligible patients will be randomized in a 1:1 ratio, with one group receiving the standard of care (SoC) BEV alone and the other group receiving treatment with microbubble-mediated FUS treatment in addition to BEV (FUS-MB+BEV). Eligible patients who assigned to the SoC group will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes). On the other hand, eligible patients assigned to treatment group will initially receive the same BEV schedule. After at least 30 minutes, patients will be administered microbubbles (MB) (SonoVue® ) at a dose of 0.1 mL/kg, along with optimal ultrasound exposure doses determined by the acoustic emission feedback FUS power control algorithm of the NaviFUS System. The treatment will be administered every 2 weeks up to 34 weeks or until evidence of progression disease (PD), intolerable toxicity precluding further treatment, non- compliance with study follow-up, or withdrawal of consent, whichever occurs first.

Spinal cord gliomas are rare primary intramedullary tumors characterized by lateralized infiltrative growth and limited treatment options beyond surgical resection. Due to the anatomical complexity and functional sensitivity of the spinal cord, the choice of surgical approach significantly impacts postoperative neurological outcomes. The traditional posterior median sulcus (PMS) approach provides direct midline access for tumor removal but carries a considerable risk of damage to central neural tracts. The dorsolateral sulcus (DLS) approach offers an alternative route for laterally located tumors, potentially sparing critical midline structures and improving functional outcomes. This single-center, registry-based cohort study aims to evaluate and compare the clinical outcomes of spinal cord glioma resections performed via the DLS and PMS approaches. Patients will be enrolled based on eligibility criteria including lateralized tumor growth confirmed by imaging and histopathology, in accordance with the 2021 WHO classification of CNS tumors. Primary and secondary outcomes will be assessed using validated clinical scales, including: Visual Analog Scale (VAS) for pain assessment McCormick Functional Grading Scale Japanese Orthopaedic Association (JOA) Score for spinal cord function SF-36 Health Survey for quality of life evaluation Functional assessment of posterior column integrity Outcome assessments will be performed at five scheduled time points: preoperatively, and postoperatively at 1 month, 3 months, 6 months, and at the last follow-up visit. The study will evaluate neurological recovery, extent of resection, tumor recurrence, postoperative complications, and overall survival. This research aims to identify the optimal surgical approach that maximizes tumor resection while preserving neurological function in patients with spinal cord gliomas.

The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma multiforme (GBM). The main question it aims to answer is: Does niraparib improve overall survival (OS) compared to TMZ? Participants will be randomly assigned to one of two treatment arms: niraparib or TMZ. * study drug (Niraparib) or * comparator drug (Temozolomide - which is the standard approved treatment for MGMT unmethylated glioblastoma). The study medication will be taken daily while receiving standard of care radiation therapy (RT) for 6-7 weeks. Participants may continue to take the niraparib or TMZ adjuvantly as long as the cancer does not get worse or completion of 6 cycles of treatment (TMZ). A total of 450 participants will be enrolled in the study. Participants' tasks will include: * Complete study visits as scheduled * Complete a diary to record study medication