Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma

Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response.

Increasing importance of 18F-FDG PET in the diagnosis of neurolymphomatosis

Item does not contain fulltextNeurolymphomatosis (NL) is a rare clinical entity that is defined as infiltration of the nervous system by a known or unknown haematological malignancy and is difficult to diagnose. Fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging is increasingly being used in haematological malignancies. This article focus on the role of 18F-FDG PET in the diagnosis and management of NL by presenting a review of cases described in the literature. Reports on NL that used PET with or without computed tomography (CT) as a diagnostic modality were extracted from Medline and evaluated. A total of 58 patients described in 49 case reports on NL were found. In 36 distinctive patients 18F-FDG PET with or without CT was used as a diagnostic modality. In 91% of patients PET showed uptake in various structures in the central or peripheral nervous system, suggesting involvement of lymphoma. Predilection localizations were the brachial and lumbar plexuses, along the course of peripheral nerves of the extremities, and the trigeminal nerve root. MRI, cerebrospinal fluid or bone marrow analysis were frequently negative. In the cases described in the literature 18F-FDG PET assisted in diagnosing NL by providing a whole-body evaluation, showing frequent uptake in affected nervous structures and supported disease management by defining a target for biopsy, monitoring progression and evaluating response to treatment. As other diagnostic methods may be negative, the importance of PET-CT is increasing in the diagnosis and management of this rare clinical entity

Dosimetry methods and clinical applications in peptide receptor radionuclide therapy for neuroendocrine tumours: a literature review

Contains fulltext : 196897.pdf (publisher's version ) (Open Access)BACKGROUND: The main challenge for systemic radiation therapy using radiopharmaceuticals (SRT) is to optimise the dose delivered to the tumour, while minimising normal tissue irradiation. Dosimetry could help to increase therapy response and decrease toxicity after SRT by individual treatment planning. Peptide receptor radionuclide therapy (PRRT) is an accepted SRT treatment option for irresectable and metastatic neuroendocrine tumours (NET). However, dosimetry in PRRT is not routinely performed, mainly due to the lack of evidence in literature and clinical implementation difficulties. The goal of this review is to provide insight in dosimetry methods and requirements and to present an overview of clinical aspects of dosimetry in PRRT for NET. METHODS: A PubMed query including the search criteria dosimetry, radiation dose, peptide receptor radionuclide therapy, and radionuclide therapy was performed. Articles were selected based on title and abstract, and description of dosimetric approach. RESULTS: A total of 288 original articles were included. The most important dosimetry methods, their main advantages and limitations, and implications in the clinical setting are discussed. An overview of dosimetry in clinical studies regarding PRRT treatment for NET is provided. CONCLUSION: Clinical dosimetry in PRRT is feasible and can result in improved treatment outcomes. Current clinical dosimetry studies focus on safety and apply non-voxel-based dosimetry methods. Personalised treatment using sophisticated dosimetry methods to assess tumour and normal tissue uptake in clinical trials is the next step towards routine dosimetry in PRRT for NET

The Effects of Early and Late Scanning on Image Quality and Functional Parameters in Myocardial Perfusion Imaging

Materials and Methods: Timing of acquisition is a factor that may influence the subdiaphragmatic activity in myocardial perfusion scintigraphy (MPS). According to the instructions of tetrofosmin, scintigraphy may already be started 15 minutes postinjection. The aim of the present study was to compare the image quality and the functional parameters between early and late scanning. Eventually, 49 consecutive patients underwent a 2-day MPS protocol in which 15 and 45 minutes after the injection of 500 MBq of technetium-99m-tetrofosmin scintigraphy both at stress and rest were performed. The amount of subdiaphragmatic tracer activity was scored from "no tracer activity" to "severe." Moderate and severe subdiaphragmatic tracer activity was considered relevant for the interpretation of the myocardial perfusion scan. Results: Two-thirds of the patients (64%) showed a considerable amount of subdiaphragmatic activity on the 15 minutes rest images, whereas only 9 patients (18%) had considerable subdiaphragmatic activity on the late images. Stress imaging showed comparable results, however, subdiaphragmatic activity was generally less frequent and less prominent following stress. The value of the ejection fraction was significantly lower during early imaging comparing with late imaging. Lower ejection fraction was exclusively noticed in imaging with moderate and severe subdiaphragmatic tracer activity related wrong border estimation. Conclusions: Acquisition 15 minutes after the injection of Tetrofosmin shows a significant and clinically relevant subdiaphragmatic activity in most myocardial perfusion scans leading to poorer image quality and to an erroneous measurement of the ejection fraction. Therefore, early acquisition in MPS is not recommended in clinical practice.Cardiovascular Aspects of Radiolog

SPECT/CT for Anatomical Mapping of Lymphatic Drainage in Vulvar Cancer: Possible Implications for the Extent of Inguinal Lymph Node Dissection

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

The use of SPECT/CT for anatomical mapping of lymphatic drainage in vulvar cancer: possible implications for the extent of inguinal lymph node dissection

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas