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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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Carbon ion radiotherapy boost in the treatment of glioblastoma: a randomized phase I/III clinical trial.
Kong, L, Gao, J, Hu, J, Lu, R, Yang, J, Qiu, X, Hu, W, Lu, JJ
Cancer communications (London, England). 2019;(1):5
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Abstract
BACKGROUND Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy. METHODS AND DESIGN Patients with newly diagnosed malignant gliomas will have their tumor tissue samples submitted for the analysis of the status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. In Phase I, the patients will undergo an induction carbon ion radiotherapy (CIRT) boost followed by 60 GyE of proton irradiation with concurrent temozolomide (TMZ) at 75 mg/m2. To determine the maximal dose of safe induction boost, the tolerance, and acute toxicity rates in a dose-escalation manner from 9 to 18 GyE in three fractions will be used. In Phase III, GBM-only patients will be randomized to receive either 60 GyE (2 GyE per fraction) of proton irradiation with concurrent TMZ (control arm) or a CIRT boost (dose determined in Phase I of this trial) followed by 60 GyE of proton irradiation with concurrent TMZ. The primary endpoints are overall survival (OS) and toxicity rates (acute and long-term). Secondary endpoints are progression-free survival (PFS), and tumor response (based upon assessment with C-methionine/fluoro-ethyl-tyrosine positron emission tomography [MET/FET PET] or magnetic resonance imaging [MRI] and detection of serologic immune markers). We hypothesize that the induction CIRT boost will result in a greater initial tumor-killing ability and prime the tumor microenvironment for enhanced immunologic tumor clearance, resulting in an expected 33% improvement in OS rates. DISCUSSION The prognosis of GBM remains grim. The mechanism underpinning the poor prognosis of this malignancy is its chronic state of tumor hypoxia, which promotes both immunosuppression/immunologic evasion and radio-resistance. The unique physical and biological properties of CIRT are expected to overcome these microenvironmental limitations to confer an improved tumor-killing ability and anti-tumor immune response, which could result in an improvement in OS with minimal toxicity. Trial registration number This trial has been registered with the China Clinical Trials Registry, and was allocated the number ChiCTR-OID-17013702.
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Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and nonbrainstem gliomas.
Pollack, IF, Jakacki, RI, Butterfield, LH, Hamilton, RL, Panigrahy, A, Potter, DM, Connelly, AK, Dibridge, SA, Whiteside, TL, Okada, H
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014;(19):2050-8
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Abstract
PURPOSE Diffuse brainstem gliomas (BSGs) and other high-grade gliomas (HGGs) of childhood carry a dismal prognosis despite current treatments, and new therapies are needed. Having identified a series of glioma-associated antigens (GAAs) commonly overexpressed in pediatric gliomas, we initiated a pilot study of subcutaneous vaccinations with GAA epitope peptides in HLA-A2-positive children with newly diagnosed BSG and HGG. PATIENTS AND METHODS GAAs were EphA2, interleukin-13 receptor alpha 2 (IL-13Rα2), and survivin, and their peptide epitopes were emulsified in Montanide-ISA-51 and given every 3 weeks with intramuscular polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose for eight courses, followed by booster vaccinations every 6 weeks. Primary end points were safety and T-cell responses against vaccine-targeted GAA epitopes. Treatment response was evaluated clinically and by magnetic resonance imaging. RESULTS Twenty-six children were enrolled, 14 with newly diagnosed BSG treated with irradiation and 12 with newly diagnosed BSG or HGG treated with irradiation and concurrent chemotherapy. No dose-limiting non-CNS toxicity was encountered. Five children had symptomatic pseudoprogression, which responded to dexamethasone and was associated with prolonged survival. Only two patients had progressive disease during the first two vaccine courses; 19 had stable disease, two had partial responses, one had a minor response, and two had prolonged disease-free status after surgery. Enzyme-linked immunosorbent spot analysis in 21 children showed positive anti-GAA immune responses in 13: to IL-13Rα2 in 10, EphA2 in 11, and survivin in three. CONCLUSION GAA peptide vaccination in children with gliomas is generally well tolerated and has preliminary evidence of immunologic and clinical responses. Careful monitoring and management of pseudoprogression is essential.