Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Borderline Findings in -(2-[F]-Fluoroethyl)-l-Tyrosine PET of Patients with Suspected Glioma Relapse: Role in Clinical Practice.

One of the most common clinical indications for amino acid PET using the tracer -(2-[F]-fluoroethyl)-l-tyrosine (F-FET) is the differentiation of tumor relapse from treatment-related changes in patients with gliomas. A subset of patients may present with an uptake of F-FET close to recommended threshold values. The goal of this study was to investigate the frequency of borderline cases and the role of quantitative F-FET PET parameters in this situation.

The Value of Multidisciplinary Neuro-oncological Tumor Boards to Increase the Accuracy of FET PET for Identifying Brain Tumor Relapse.

Purpose: Especially in Europe, amino acid PET is increasingly integrated into multidisciplinary neuro-oncological tumor boards (MNTBs) to overcome diagnostic uncertainties such as treatment-related changes. We evaluated the accuracy of MNTB decisions that included the O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET information compared with FET PET results alone to differentiate tumor relapse from treatment-related changes.

Patients And Methods: In a single academic center, we retrospectively evaluated 180 MNTB decisions of 151 patients with CNS WHO grade 3 or 4 gliomas (n = 122) or brain metastases (n = 29) presenting equivocal MRI findings following anticancer treatment.

Evaluation of early metabolic changes following vorasidenib using FET PET in patients with -mutant gliomas.

The phase-3 INDIGO trial demonstrated that the isocitrate dehydrogenase () inhibitor vorasidenib significantly prolonged progression-free survival and delayed intervention in patients with CNS WHO grade 2 gliomas. However, conventional MRI showed limited response, with only 11% of patients having objective responses. Studies suggest that serial PET imaging with radiolabeled amino acids, such as -(2-[ F]-fluoroethyl)-L-tyrosine (FET) PET, may provide earlier and more informative assessments of treatment response than MRI.

Glutamate Signaling in Patients With Parkinson Disease With REM Sleep Behavior Disorder.

Background And Objectives: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive.

Clinical Applications of Radiomics in Nuclear Medicine.

Radiomics is an emerging field of artificial intelligence that focuses on the extraction and analysis of quantitative features such as intensity, shape, texture and spatial relationships from medical images. These features, often imperceptible to the human eye, can reveal complex patterns and biological insights. They can also be combined with clinical data to create predictive models using machine learning to improve disease characterization in nuclear medicine.

Hybrid PET/MRI in Cerebral Glioma: Current Status and Perspectives.

Advanced MRI methods and PET using radiolabelled amino acids provide valuable information, in addition to conventional MR imaging, for brain tumour diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumour progression from treatment-related changes, and the early assessment of responses to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing, and has been addressed in numerous studies.

High uptake of Ga-PSMA and F-DCFPyL in the peritumoral area of rat gliomas due to activated astrocytes.

Background: Recent studies reported on high uptake of the PSMA ligands [Ga]HBED-CC (Ga-PSMA) and F-DCFPyL in cerebral gliomas. This study explores the regional uptake and cellular targets of Ga-PSMA and F-DCFPyL in three different rat glioma models.

Methods: F98, 9 L, or U87 rat gliomas were implanted into the brains of 38 rats.

Current trends in the use of O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET) in neurooncology.

The diagnostic potential of PET using the amino acid analogue O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET) in brain tumor diagnostics has been proven in many studies during the last two decades and is still the subject of multiple studies every year. In addition to standard magnetic resonance imaging (MRI), positron emission tomography (PET) using [F]FET provides important diagnostic data concerning brain tumor delineation, therapy planning, treatment monitoring, and improved differentiation between treatment-related changes and tumor recurrence. The pharmacokinetics, uptake mechanisms and metabolism have been well described in various preclinical studies.

Flare Phenomenon in -(2-F-Fluoroethyl)-l-Tyrosine PET After Resection of Gliomas.

PET using -(2-F-fluoroethyl)-l-tyrosine (F-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes in F-FET uptake at the rim of the resection cavity within the first 2 wk after resection of gliomas. In the present study, we evaluated pre- and postoperative F-FET PET scans of glioma patients with particular emphasis on the identification of reactive changes after surgery.

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia.

Background: Cachexia, highly prevalent in patients with non-small cell lung cancer (NSCLC), impairs quality of life and is associated with reduced tolerance and responsiveness to cancer therapy and decreased survival. MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in post-transcriptional gene regulation. Changes in intramuscular levels of miRNAs have been implicated in muscle wasting conditions.

Treatment-Related Uptake of -(2-F-Fluoroethyl)-l-Tyrosine and l-[Methyl-H]-Methionine After Tumor Resection in Rat Glioma Models.

Assessment of residual tumor after resection of cerebral gliomas can be difficult with MRI and may be improved by amino acid PET. The aim of this experimental study was to investigate uptake of 2-F-fluoroethyl-l-tyrosine (F-FET) and l-[methyl-H]-methionine (H-MET) in residual tumor after surgery and possible false-positive uptake in treatment-related changes. F98 or GS-9L rat gliomas were implanted into the brain of 64 rats.

Combined Amino Acid Positron Emission Tomography and Advanced Magnetic Resonance Imaging in Glioma Patients.

Imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) provide valuable information about brain tumor patients. Particularly amino acid PET, advanced MRI techniques, and combinations thereof are of great interest for the non-invasive assessment of biological characteristics in patients with primary or secondary brain cancer. A methodological innovation that potentially advances research in patients with brain tumors is the increasing availability of hybrid PET/MRI systems, which enables the simultaneous acquisition of both imaging modalities.

Influence of Dexamethasone on O-(2-[F]-Fluoroethyl)-L-Tyrosine Uptake in the Human Brain and Quantification of Tumor Uptake.

Purpose: O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [F]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR).

Procedures: [F]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women).

Investigation of cis-4-[F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment.

Purpose: Cis-4-[F]fluoro-D-proline (D-cis-[F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[F]FPro in human brain tumors after multimodal treatment.

Procedures: In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases).

Relevant tumor sink effect in prostate cancer patients receiving 177Lu-PSMA-617 radioligand therapy.

Aim: In metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in Lu-PSMA-617 therapy was evaluated.

Methods: Eleven consecutive prostate cancer patients receiving a first cylcle of Lu-PSMA-617 (administered activity of approximately 6GBq) were included.

Comparison of F-FET PET and perfusion-weighted MRI for glioma grading: a hybrid PET/MR study.

Purpose: Both perfusion-weighted MR imaging (PWI) and O-(2-F-fluoroethyl)-L-tyrosine PET (F-FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of F-FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner.

Methods: Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with F-FET PET and PWI using a hybrid PET/MR scanner.

O-(2-[F]fluoroethyl)-L-tyrosine PET in gliomas: influence of data processing in different centres.

Background: PET using O-(2-[F]fluoroethyl)-L-tyrosine (F-FET) is an established method for brain tumour diagnostics, but data processing varies in different centres. This study analyses the influence of methodological differences between two centres for tumour characterization with F-FET PET using the same PET scanner. Methodological differences between centres A and B in the evaluation of F-FET PET data were identified for (1) framing of PET dynamic data, (2) data reconstruction, (3) cut-off values for tumour delineation to determine tumour-to-brain ratios (TBR) and tumour volume (T) and (4) ROI definition to determine time activity curves (TACs) in the tumour.

Imaging of amino acid transport in brain tumours: Positron emission tomography with O-(2-[F]fluoroethyl)-L-tyrosine (FET).

The assessment of cerebral gliomas using magnetic resonance imaging (MRI) provides excellent structural images but cannot solve all diagnostic problems satisfactorily. The differentiation of tumour tissue from non-neoplastic changes may be difficult especially in the post-treatment phase. In recent years, positron emission tomography (PET) using radiolabelled amino acids has gained considerable interest as an additional tool to improve the diagnosis of cerebral gliomas and brain metastases.

Outcome-Driven Thresholds for Increased Home Blood Pressure Variability.

Increased blood pressure (BP) variability predicts cardiovascular disease, but lack of operational thresholds limits its use in clinical practice. Our aim was to define outcome-driven thresholds for increased day-to-day home BP variability. We studied a population-based sample of 6238 individuals (mean age 60.

Influence of Bevacizumab on Blood-Brain Barrier Permeability and -(2-F-Fluoroethyl)-l-Tyrosine Uptake in Rat Gliomas.

Restoration of the blood-brain barrier (BBB) after antiangiogenic therapy of gliomas with bevacizumab may result in a decrease in contrast enhancement on MRI despite tumor progression. This so-called pseudoresponse is difficult to differentiate from a true tumor response with conventional MRI. Initial patient studies have indicated that PET using -(2-F-fluoroethyl)-l-tyrosine (F-FET) may be helpful for solving this diagnostic problem.