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1.
18F-Fluciclovine (18F-FACBC) PET/CT or PET/MRI in gliomas/glioblastomas.
Albano, D, Tomasini, D, Bonù, M, Giubbini, R, Bertagna, F
Annals of nuclear medicine. 2020;(2):81-86
Abstract
18F-fluciclovine (18F-FACBC) is a radiotracer already studied for prostate cancer, and its potential role in brain tumors (such as glioma) is not yet well investigated despite promising results. The aim of this review is to evaluate the possible diagnostic role of 18F-FACBC PET/CT or PET/MRI in patients with gliomas and glioblastomas. A comprehensive literature search of the PubMed/MEDLINE, Scopus, Embase, and Cochrane library databases was conducted to find the relevant published articles about the diagnostic performance of FACBC PET/CT or PET/MRI in patients affected by glioma and/or glioblastoma. Seven papers were included in the systematic review. From the analyses of the selected studies, the following main findings were obtained: glioma and glioblastoma are FACBC-avid tumors with a detection rate of about 100%; FACBC PET has high-diagnostic accuracy in defining tumor extent, volumes, and satellite lesions better than MR; compared to methionine, FACBC has similar accuracy but better tumor-to-background contrast; FACBC uptake may help to discriminate between low-grade and high-grade glioma. Radiolabelled fluciclovine (18F-FACBC) imaging seems to be useful in analyzing glioma/glioblastoma. Further studies enrolling a wider population are needed to clarify the real clinical and diagnostic role of 18F-FACBC in this setting and its possible position in the diagnostic flowchart.
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2.
Trace Element Concentration Changes in Brain Tumors: A Review.
Cilliers, K, Muller, CJF, Page, BJ
Anatomical record (Hoboken, N.J. : 2007). 2020;(5):1293-1299
Abstract
Trace elements have been implicated in cancer, since the levels differ between cancerous and noncancerous tissue, different cancer types, and different malignancy grades. However, few studies have been conducted on trace element concentrations in brain tumors. Thus, this study aims to review the available literature on trace element changes related to brain tumors, and to identify gaps in the literature. A literature search was done on Google Scholar and PubMed from their start date to January 2018, using terms related to trace element concentration and brain tumors. All brain tumor types were included, and articles could be published in any year. From this search, only 11 articles on this topic could be found. Tumors had significantly higher concentrations of arsenic, thorium, lanthanum, lutetium, cerium, and gadolinium compared to control brain samples. Compared to adjacent tissue, tumor tissue indicated increased magnesium, decreased copper, and contradicting results for zinc. Furthermore, the higher the malignancy grade, the lower the calcium, cadmium, iron, phosphorus and sulfur concentration, and the higher the mercury, manganese, lead, and zinc concentrations. In conclusion, altered trace element levels differ amongst different tumor types, as well as malignancy grades. Consequently, it is impossible to compare data from these studies, and available data are still considerably inconclusive. Ideally, future studies should have a sufficient samples size, compare different tumor types, and compare tumors with adjacent healthy tissue as well as with samples from unaffected matched brains. Anat Rec, 303:1293-1299, 2020. © 2019 American Association for Anatomy.
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Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study.
Martin-McGill, KJ, Marson, AG, Tudur Smith, C, Young, B, Mills, SJ, Cherry, MG, Jenkinson, MD
Journal of neuro-oncology. 2020;(1):213-227
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Abstract
PURPOSE We conducted a feasibility study to investigate the use of ketogenic diets (KDs) as an adjuvant therapy for patients with glioblastoma (GBM), investigating (i) trial feasibility; (ii) potential impacts of the trial on patients' quality of life and health; (iii) patients' perspectives of their decision-making when invited to participate in the trial and (iv) recommending improvements to optimize future phase III trials. METHODS A single-center, prospective, randomized, pilot study (KEATING), with an embedded qualitative design. Twelve newly diagnosed patients with GBM were randomized 1:1 to modified ketogenic diet (MKD) or medium chain triglyceride ketogenic diet (MCTKD). Primary outcome was retention at three months. Semi-structured interviews were conducted with a purposive sample of patients and caregivers (n = 15). Descriptive statistics were used for quantitative outcomes and qualitative data were analyzed thematically aided by NVivo. RESULTS KEATING achieved recruitment targets, but the recruitment rate was low (28.6%). Retention was poor; only four of 12 patients completed the three-month diet (MCTKD n = 3; MKD n = 1). Participants' decisions were intuitive and emotional; caregivers supported diet implementation and influenced the patients' decision to participate. Those who declined made a deliberative and considered decision factoring diet burden and quality of life. A three-month diet was undesirable to patients who declined and withdrew. CONCLUSION Recruitment to a KD trial for patients with GBM is possible. A six-week intervention period is proposed for a phase III trial. The role of caregivers should not be underestimated. Future trials should optimize and adequately support the decision-making of patients.
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Quercetin: A promising phytochemical for the treatment of glioblastoma multiforme.
Tavana, E, Mollazadeh, H, Mohtashami, E, Modaresi, SMS, Hosseini, A, Sabri, H, Soltani, A, Javid, H, Afshari, AR, Sahebkar, A
BioFactors (Oxford, England). 2020;(3):356-366
Abstract
Quercetin, a plant-derived flavonoid, is known for its antitumor and antiproliferative activities. Glioblastoma multiforme (GBM), as a highly aggressive cerebrum tumor, has a poor prognosis that is approximately 12 months despite standard therapy. Therefore, because of the low effectiveness of the current therapeutic strategies, additional medications in combination with chemotherapy and radiotherapy are needed, which could improve the prognosis of GBM patients. Multiple lines of evidence have shown that quercetin regulates many proteins involved in the cellular signal transduction in GBM. In this review, recent findings on the targeting of particular signaling pathways by quercetin and the subsequent effect on the pathogenesis of GBM are presented and discussed.
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Ependymal fluorescence in fluorescence-guided resection of malignant glioma: a systematic review.
Müther, M, Stummer, W
Acta neurochirurgica. 2020;(2):365-372
Abstract
BACKGROUND Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas infiltrate the ventricles. However, the underlying pathophysiology and clinical importance are largely unknown but may play a role in deciding whether to continue resection into the ventricles or not. Here, we systematically review available data regarding ependymal fluorescence in FGR using five aminolevulinic acid (5-ALA) and sodium fluorescein (SF). METHODS A literature search on MEDLINE, EMBASE, and WEB OF SCIENCE was performed using the following headings and search operators: ependy* fluorescence AND (5-ALA OR five aminolevulinic acid), ventric* wall fluorescence AND (5-ALA OR five aminolevulinic acid), ependy* fluorescence AND fluorescein, and ventric* wall fluorescence AND fluorescein. Both authors analyzed abstracts independently. Included articles were further reviewed for prevalence of ependymal fluorescence, patterns of fluorescence, and histopathological characteristics of sampled tissues as well as radiological signs of ependymal fluorescence. Results are reported according to the PRISMA statement. RESULTS Of 202 records identified, 6 studies were included compiling a total number of 198 patients treated with FGR using 5-ALA. No study on ependymal fluorescence after administration of SF was found. Overall prevalence of ependymal fluorescence was 61.4%. A total of 54.5% of cases were found to be positive for tumor cells. A total of 25.5% of patients with ependymal fluorescence were related to contrast enhancement in ventricular walls. CONCLUSIONS The phenomenon of ventricular wall fluorescence in 5-ALA-derived fluorescence-guided resection of malignant glioma is poorly understood and not always may fluorescence represent tumor infiltration. A larger scale prospective sampling study with molecular analyses is currently ongoing and will hopefully provide further insight into pathophysiology and clinical implications of ependymal fluorescence.
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Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors.
Werner, JM, Lohmann, P, Fink, GR, Langen, KJ, Galldiks, N
Molecules (Basel, Switzerland). 2020;(6)
Abstract
The number of positron-emission tomography (PET) tracers used to evaluate patients with brain tumors has increased substantially over the last years. For the management of patients with brain tumors, the most important indications are the delineation of tumor extent (e.g., for planning of resection or radiotherapy), the assessment of treatment response to systemic treatment options such as alkylating chemotherapy, and the differentiation of treatment-related changes (e.g., pseudoprogression or radiation necrosis) from tumor progression. Furthermore, newer PET imaging approaches aim to address the need for noninvasive assessment of tumoral immune cell infiltration and response to immunotherapies (e.g., T-cell imaging). This review summarizes the clinical value of the landscape of tracers that have been used in recent years for the above-mentioned indications and also provides an overview of promising newer tracers for this group of patients.
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Usefulness of 18F-FDOPA PET for the management of primary brain tumors: a systematic review of the literature.
Somme, F, Bender, L, Namer, IJ, Noël, G, Bund, C
Cancer imaging : the official publication of the International Cancer Imaging Society. 2020;(1):70
Abstract
Contrast-enhanced magnetic resonance imaging is currently the standard of care in the management of primary brain tumors, although certain limitations remain. Metabolic imaging has proven useful for an increasing number of indications in oncology over the past few years, most particularly 18F-FDG PET/CT. In neuro-oncology, 18F-FDG was insufficient to clearly evaluate brain tumors. Amino-acid radiotracers such as 18F-FDOPA were then evaluated in the management of brain diseases, notably tumoral diseases. Even though European guidelines on the use of amino-acid PET in gliomas have been published, it is crucial that future studies standardize acquisition and interpretation parameters. The aim of this article was to systematically review the potential effect of this metabolic imaging technique in numerous steps of the disease: primary and recurrence diagnosis, grading, local and systemic treatment assessment, and prognosis. A total of 41 articles were included and analyzed in this review. It appears that 18F-FDOPA PET holds promise as an effective additional tool in the management of gliomas. More consistent prospective studies are still needed.
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Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma.
Kaley, TJ, Panageas, KS, Pentsova, EI, Mellinghoff, IK, Nolan, C, Gavrilovic, I, DeAngelis, LM, Abrey, LE, Holland, EC, Omuro, A, et al
Annals of clinical and translational neurology. 2020;(4):429-436
Abstract
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. Therefore, we initiated a phase I trial of combined therapy in recurrent MGs to determine safety and a recommended phase II dose. METHODS Adults with recurrent MG, Karnofsky Performance Status ≥ 60 were enrolled, with no limit on the number of prior therapies. Temsirolimus dose was escalated using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. Perifosine was fixed as a 600 mg load on day 1 followed by 100 mg nightly (single agent MTD) until dose level 7 when the load increased to 900 mg. RESULTS We treated 35 patients with with glioblastoma (17) or other MGs (18; including nine anaplastic astrocytoma, nine anaplastic oligodendroglioma, one anaplastic oligoastrocytoma, and two low grade astrocytomas with radiographic transformation to MG). We observed five dose-limiting toxicities (DLTs): one at dose level 3 (50mg temsirolimus), then two at dose level 7 expansion (170 mg temsirolimus), and then two more at dose level 6 expansion (170 mg temsirolimus). DLTs included thrombocytopenia (n = 3), intracerebral hemorrhage (n = 1) and lung infection (n = 1). CONCLUSION Combining the mTOR inhibitor temsirolimus dosed at 115 mg weekly and the AKT inhibitor perifosine dosed at 100 mg daily (following 600 mg load) is tolerable in heavily pretreated adults with recurrent MGs.
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A novel three-dimensional template combined with MR-guided 125I brachytherapy for recurrent glioblastoma.
He, X, Liu, M, Zhang, M, Sequeiros, RB, Xu, Y, Wang, L, Liu, C, Wang, Q, Zhang, K, Li, C
Radiation oncology (London, England). 2020;(1):146
Abstract
BACKGROUND At present, the treatment of recurrent glioblastoma is extremely challenging. In this study, we used a novel three-dimensional non-coplanar template (3DNPT) combined with open MR to guide 125I seed implantation for recurrent glioblastoma. The aim of this study was to evaluate the feasibility, accuracy, and effectiveness of this technique. METHODS Twenty-four patients of recurrent glioblastoma underwent 3DNPT with open MR-guided 125I brachytherapy from August 2017 to January 2019. Preoperative treatment plan and 3DNPT were made according to enhanced isovoxel T1-weighted MR images. 125I seeds were implanted using 3DNPT and 1.0-T open MR imaging guidance. Dosimetry verification was performed after brachytherapy based on postoperative CT/MR fusion images. Preoperative and postoperative dosimetry parameters of D90, V100, V200, conformity index (CI), external index (EI) were compared. The objective response rate (ORR) at 6 months and 1-year survival rate were calculated. Median overall survival (OS) measured from the date of brachytherapy was estimated by Kaplan-Meier method. RESULTS There were no significant differences between preoperative and postoperative dosimetry parameters of D90, V100, V200, CI, EI (P > 0.05). The ORR at 6 months was 75.0%. The 1-year survival rate was 58.3%. Median OS was 12.9 months. One case of small amount of epidural hemorrhage occurred during the procedure. There were 3 cases of symptomatic brain edema after brachytherapy treatment, including grade three toxicity in 1 case and grade two toxicity in 2 cases. The three patients were treated with corticosteroid for 2 to 4 weeks. The clinical symptoms related to brain edema were significantly alleviated thereafter. CONCLUSIONS 3DNPT combined with open MR-guided 125I brachytherapy for circumscribed recurrent glioblastoma is feasible, effective, and with low risk of complications. Postoperative dosimetry matched the preoperative treatment plan. The described method can be used as a novel implantation technique for 125I brachytherapy in the treatment of recurrent gliomas. TRIAL REGISTRATION The study was approved by the Institutional Review Board of Shandong Provincial Hospital Affiliated to Shandong University (NSFC:NO.2017-058), registered 1st July 2017.
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Fluorescein-guided resection of gliomas.
Save, AV, Gill, BJ, D'amico, RS, Canoll, P, Bruce, JN
Journal of neurosurgical sciences. 2019;(6):648-655
Abstract
Standard of care in the management of high-grade gliomas includes gross total resection (GTR) followed by treatment with radiation and temozolomide. GTR remains one of the few independent prognostic factors for improved survival in this disease. Sodium fluorescein is an organic fluorophore that has been studied as a surgical adjunct to improve the likelihood of achieving GTR in gliomas. Though sodium fluorescein does not selectively accumulate in glioma cells, it allows for real-time identification of regions of blood brain barrier breakdown, corresponding to the contrast-enhancing cores of high-grade gliomas. In addition to its high predictive value for identifying pathologic tissue, use of fluorescein has been shown to improve rates of GTR. In stereotactic needle biopsies, it helps reduce procedure time by rapidly confirming the presence of diagnostic tissue. Furthermore, in non-enhancing, low-grade gliomas, it labels focal regions of vascular dysregulation that have been correlated with high-grade features. Fluorescein has also been shown to be significantly less expensive than other contemporary surgical adjuncts such as intraoperative ultrasound, intraoperative MRI, and the recently FDA approved fluorophore, 5-aminolevulinic acid (5-ALA). Here, we review the current literature on the effectiveness of fluorescein as a surgical tool in the resection of gliomas.