Background: Patients with in-transit melanoma metastases (ITM) experience a diverse spectrum of clinical presentations and a highly variable disease course. There is no standardized treatment protocol for these patients due to the limited data comparing treatment modalities for ITM. This is the first study to describe the disease trajectory and natural history of a large cohort of patients with ITM.
View Article and Find Full Text PDFSome patients with metastatic differentiated thyroid cancer (DTC) lack iodine avidity and are therefore unsuitable for radioactive iodine (RAI) therapy. Limited experience suggests that single-agent selective mitogen-activated protein kinase (MAPK) pathway inhibitors can restore expression of the sodium-iodide symporter rendering RAI refractory (RAIR) DTC patients amenable to RAI therapy. The aim of this study was to assess the feasibility of mutation-guided MAPK-pathway blockade combined with thyroid hormone withdrawal (THW) for redifferentiation.
View Article and Find Full Text PDFPurpose: To describe outcomes of transrenal embolization with vascular plugs and ethylene vinyl alcohol (EVOH) in a case series of patients with refractory urinary leak or fistula.
Materials And Methods: Fifteen ureteral occlusions performed over 53 months in 9 consecutive patients (56% female; mean age 61 y; range, 45-80 y) were reviewed retrospectively. The main indication was palliation for refractory fistula or leak in the setting of malignancy not responding to urine diversion by percutaneous nephrostomy tube or nephroureteral stent.
Due to the increasing incidence and prevalence of neuroendocrine tumors (NETs), there is a need to assess any gaps in awareness and care. A survey was undertaken in 2017 to identify perceived unmet needs from the perspectives of patients/families, patient advocates and health care professionals (HCPs). The survey consisted of 33-37 questions (depending on type of respondent) across four areas: information, care, treatments and research.
View Article and Find Full Text PDFCurr Treat Options Oncol
August 2019
Neuroendocrine neoplasia (NEN) represents a heterogenous group of tumours. Guidelines regarding treatment choice and sequencing remain complex given varied primary sites, hormone-secretory status, tumour grade, disease heterogeneity, and paucity of rigorous comparative trials due to rarity of this condition. However, there is increasing evidence that peptide receptor radionuclide therapy (PRRT) is an effective treatment, especially for grade 1 and 2 NEN.
View Article and Find Full Text PDFBackground: Human induced pluripotent stem cells (hiPSC) hold great promise for use in cell therapy applications and for improved in vitro models of human disease. So far, most hiPSC differentiation protocols to astroglia use undefined, animal-containing culture matrices. Laminins, which play an essential role in the regulation of cell behavior, offer a source of defined, animal-free culture matrix.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
November 2019
Prostate-specific membrane antigen (PSMA) is expressed in most prostate cancers and can be identified by PSMA-ligand imaging, which has already become clinically accepted in several countries in- and outside Europe. PSMA-directed radioligand therapy (PSMA-RLT) with Lutetium-177 (Lu-PSMA) is currently undergoing clinical validation. Retrospective observational data have documented favourable safety and striking clinical responses.
View Article and Find Full Text PDFMolecules containing lysine-ureido-glutamate functional groups bind to the active site of prostate specific membrane antigen, which is overexpressed in prostate cancer. To prepare copper radiopharmaceuticals for the diagnosis and therapy of prostate cancer, macrobicyclic sarcophagine ligands tethered to either one or two lysine-ureido-glutamate functional groups through an appropriate linker have been prepared. Sarcophagine ligands can be readily radiolabeled with positron-emitting copper-64 at room temperature.
View Article and Find Full Text PDFTechnical advances in imaging are well demonstrated by MRI (Magnetic Resonance Imaging) and PET (Positron Emission Tomography). Excellent anatomical detail and a lack of ionising radiation make MRI the standard of care for most neuroimaging indications, and advanced sequences are providing an ever-growing ability for lesion characterisation. PET utilising the tracer fluorine-18 fluorodeoxyglucose is widely used in oncology, while newer PET tracers are able to target a growing number of metabolic pathways and cell membrane receptors.
View Article and Find Full Text PDFBackground: Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of Lu-PSMA-617 radioligand therapy in men with high PSMA expression who progressed after standard therapies.
Objective: To determine outcomes for men screened for the trial but not treated because of low PSMA expression.
Background Endothelin B receptor (ETR) is involved in melanoma pathogenesis and is overexpressed in metastatic melanoma. The antibody-drug conjugate DEDN6526A targets ETR and is comprised of the humanized anti-ETR monoclonal antibody conjugated to the anti-mitotic agent monomethyl auristatin E (MMAE). Methods This Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of DEDN6526A (0.
View Article and Find Full Text PDFDalton Trans
September 2019
A series of palladium(ii) complexes containing a redox-active, tridentate verdazyl ligand of general formula (verdazyl)PdL (L = Cl, CHCN) are synthesized. The tetrazine core of tridentate verdazyl ligand 5 is flanked by two pyridyl groups, creating a geometry in which the ancillary ligand L is bound trans to the verdazyl ring in the square planar metal complexes. Pd(ii) complexes were isolated with the verdazyl ligand in either its neutral radical charge state (6: L = CHCN, 12: L = Cl) or its closed-shell monoanionic charge state (10: L = CHCN, 9: L = Cl).
View Article and Find Full Text PDFBackground: The prognosis of patients with metastatic neuroendocrine neoplasms (NEN) continues to improve with modern oncological therapy. In the subgroup of patients with carcinoid syndrome, the development of carcinoid heart disease (CaHD) severely impacts long term survival. Valve surgery has been demonstrated to improve survival and symptoms in patients with CaHD.
View Article and Find Full Text PDFSerous carcinomas of the testis or para-testis are extremely rare tumors of Mullerian type. We report a case of high-grade serous papillary carcinoma of the tunica vaginalis, treated with radical orchiectomy and hemi-scrotectomy after being referred for a rapidly growing painless scrotal mass. In addition to negative testicular tumor markers, scrotal ultrasound, and conventional computerized tomography (CT) scanning, this patient's workup included a positron emission tomography (PET) scan using F-18-fluoro-deoxyglucose (FDG), demonstrating metabolically avid uptake of the disease.
View Article and Find Full Text PDFPurpose: Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results.
View Article and Find Full Text PDFAlthough bone-scanning agents remain important for the detection of bone metastasis, the most common site of distant disease in prostate cancer, novel molecular imaging techniques are entering into clinical practice that provide new opportunities to both detect and characterize sites of involvement by prostate cancer, particularly in the setting of recurrent or advanced metastatic disease based on biochemical, clinical or imaging criteria. These approaches can define disease burden, guide locoregional salvage therapies, and select and monitor systemic treatment. While a wide array of tracers is available, the clinical role of broad classes of agents will be reviewed.
View Article and Find Full Text PDFPurpose: Inflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS).
Methods: Retrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT.
Background: Testicular germ cell tumour is the commonest malignancy affecting males aged between 15 and 35, with an increased relative risk amongst those with a history of cryptorchidism. In patients presenting with locoregional metastatic disease, retroperitoneal and pelvic soft tissue masses are common findings on ultrasound and computed tomography, which has several differential diagnoses within this demographic cohort. On staging F-FDG-PET/CT, understanding the typical testicular lymphatic drainage pathway facilitates prompt recognition of the pathognomonic constellation of unilateral absence of testicular scrotal activity, and FDG-avid nodal masses along the drainage pathway.
View Article and Find Full Text PDFMicrobial colonization can be detrimental to the integrity of metal surfaces and lead to microbiologically influenced corrosion (MIC). Biocorrosion is a serious problem for aquatic and marine industries in the world. In Minnesota (USA), where this study was conducted, biocorrosion severely affects the maritime transportation industry.
View Article and Find Full Text PDFPurpose: Detailed data comparing the biodistribution of PSMA radioligands is still scarce, raising concerns regarding the comparability of different compounds. We investigated differences in normal-organ biodistribution and uptake variability between the two most commonly PSMA tracers in clinical use, Ga-PSMA-11 and F-DCFPyL.
Methods: This retrospective analysis included 34 patients with low tumor burden referred for PET/CT imaging with Ga-PSMA-11 and subsequently F-DCFPyL.
Introduction: Congenital myotonic dystrophy (CDM) is a rare neuromuscular disorder characterized by severe hypotonia and muscle weakness at birth that tends to improve with age. Understanding lean body and bone mass in this population has important research and clinical implications. The main objective of this study was to determine whether older children with CDM had muscle mass similar to healthy controls.
View Article and Find Full Text PDFObjective: To test whether systemic cytokine release is associated with central nervous system inflammatory responses and glial injury in immune effector cell-associated neurotoxicity syndrome (ICANS) after chimeric antigen receptor (CAR)-T cell therapy in children and young adults.
Methods: We performed a prospective cohort study of clinical manifestations as well as imaging, pathology, CSF, and blood biomarkers on 43 subjects ages 1 to 25 who received CD19-directed CAR/T cells for acute lymphoblastic leukemia (ALL).
Results: Neurotoxicity occurred in 19 of 43 (44%) subjects.