Ringlike pattern as a dermatoscopy sign for vulvar melanosis does not preclude synchronous existence of vulvar melanoma.
J Eur Acad Dermatol Venereol. 2019 Mar 21;:
Authors: Dobrosavljevic D, Brasanac D, Lukic S, Kosovac O, Radlovic P, Stilet A, Vukicevic J, Rzodic R
Vulvar melanoma (VM) accounts for 1-3% of all melanoma arising in women with poor long-term clinical outcome.1,2 VM can be uni- or multifocal.3-5 Multifocality is defined as multiple foci of melanoma separated by intact epithelium, or arising on follow-up, outside the vicinity of the surgical scar. This article is protected by copyright. All rights reserved.
PMID: 30897233 [PubMed - as supplied by publisher]
A Metal-Free DOTA-Conjugated 18F-Labeled Radiotracer: [18F]DOTA-AMBF3-LLP2A for Imaging VLA-4 Over-Expression in Murine Melanoma with Improved Tumor Uptake and Greatly Enhanced Renal Clearance.
Bioconjug Chem. 2019 Mar 21;:
Authors: Roxin A, Zhang C, Huh S, Lepage ML, Zhang Z, Lin KS, Bénard F, Perrin DM
DOTA is commonly used for radiometal chelation in molecular imaging. Yet in the absence of a radiometal, DOTA is hypothesized to promote renal clearance of 18F-labeled peptide tracers. In light of an increasing interest in the use of F18 for PET, here the effect of DOTA is evaluated for the first time with an 18F-labeled tracer and is found to significantly improve the quality of images acquired through positron emission tomography (PET). We chose to image the peptide LLP2A that recognizes the transmembrane protein very-late antigen 4 (VLA-4) that is overexpressed by many cancers. Since it is known that [18F]RBF3-PEG2-LLP2A derivatives gave low tumor uptake values and significant GI tract accumulation, this ligand thus represents an ideal means of testing the additive effects of a DOTA group on clearance while permitting a facile, user-friendly, one-step 18F-labeling. A newly designed RBF3-LLP2A bioconjugate with an appended DOTA moiety increased tumor uptake nearly 3-fold and reduced GI accumulation by more than 10-fold. The DOTA-AMBF3-PEG2-LLP2A was radiolabeled by isotope exchange and was purified by semi-prep HPLC and C18 cartridge elution. Male C57BL/6J mice bearing B16-F10 melanoma tumors that overexpress the VLA-4 target were used to evaluate [18F]DOTA-AMBF3-PEG2-LLP2A using a combination of static and dynamic PET scans, biodistribution studies and blocking controls at 1h post injection (p.i.). The precursor peptide was synthesized and 18F-labeled to provide formulations with mean (±SD) radiochemical purities of 95.9 ± 1.8 %, in radiochemical yields of 4.8 ± 2.9 % having molar activities of 131.7 ± 50.3 GBq/μmol. In vivo static PET images of [18F]DOTA-AMBF3-PEG2-LLP2A provided clear tumor visualization, and biodistribution studies showed that tumor uptake was 9.46 ± 2.19 percent injected dose per gram of tissue (%ID/g) with high tumor:muscle and tumor:blood contrast ratios of ~8 and ~10, respectively. Blocking confirmed the specificity of [18F]DOTA-AMBF3-PEG2-LLP2A to VLA-4 in the tumor and the bone marrow. Dynamic PET showed clearance of [18F]DOTA-AMBF3-PEG2-LLP2A mainly via the renal pathway, wherein accumulation in the intestines was reduced 10-fold compared to our previously investigated LLP2A's, while spleen uptake was at levels similar to previously reported LLP2A-chelator radiotracers. [18F]DOTA-AMBF3-PEG2-LLP2A represents a promising VLA-4 radiotracer and provides key evidence as to how a DOTA appendage can significantly reduce GI-uptake in favor of urinary excretion. Implications for the development of dual-isotope theranostics that exploit the use fluorine-18 for imaging and DOTA to chelate therapeutic metal cations for therapy are discussed.
PMID: 30896929 [PubMed - as supplied by publisher]
The Need for Increased Melanoma Awareness among Non-dermatology Secondary Care Colleagues.
Acta Derm Venereol. 2019 Mar 21;:
Authors: Quinlan C, McCracken S, Tierney E, Heffron C, Fitzgibbon J, Murphy C, Bourke JF, Murphy M
PMID: 30896782 [PubMed - as supplied by publisher]
Outcomes Associated With Sustained-Release Intraocular Fluocinolone Implants in a Case of Melanoma-Associated Retinopathy Treated Without Systemic Immunosuppression.
JAMA Ophthalmol. 2019 Mar 21;:
Authors: Karatsai E, Robson AG, Taylor SRJ
Importance: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome in which antiretinal antibodies crossreact with retinal ON-bipolar cells, resulting in night blindness and progressive visual field loss. Current therapeutic options include cytoreductive surgery in combination with immunoglobulin, corticosteroids, or plasmapheresis, but their effectiveness is limited and may be contraindicated, given the possible protective role of circulating autoantibodies against metastatic spread. We report 3-year follow-up of the first case (to our knowledge) of MAR treated with intravitreal long-acting steroid implants.
Objective: To report on a patient with MAR who was treated with intravitreal fluocinolone acetonide implants in the absence of systemic immunosuppression.
Design, Setting, and Participants: This is a 3-year follow-up of a 73-year-old woman with a history of surgical excision of a malignant melanoma of the left pinna who presented with visual symptoms of shimmering and nyctalopia. Fundus examination, fundus autofluorescence, and optical coherence tomography were normal, with no evidence of cystoid macular edema. Automated perimetry showed a reduction in visual field and full-field electroretinography (ERG) demonstrated findings consistent with generalized ON-bipolar cell dysfunction, typical of MAR. The patient was treated with bilateral fluocinolone acetonide intravitreal implants.
Main Outcomes and Measures: Visual acuity, visual field, and electroretinography testing for 3 years after treatment.
Results: Visual fields improved in this 73-year-old patient from 20/30 (Snellen measured as 6/9) OD and 20/16 (6/5) OS at baseline to 20/20 OU within 1 week of treatment. Detailed electroretinography monitoring indicated characteristic abnormalities that partly resolved after treatment, consistent with improved inner retinal ON-bipolar cell function. Bilateral cataracts developed approximately 2 years after injection; cataract surgery was performed uneventfully. At 3 years posttreatment, the patient remained visually stable and in systemic disease remission, with best-corrected visual acuity remaining at 20/20 OU.
Conclusions and Relevance: We report what is, to our knowledge, the first case of MAR treated with intravitreal slow-release corticosteroid implants, which shows improvements in visual symptoms, visual fields, and retinal function. Sustained-release intraocular steroid implants may offer an effective and safe alternative to systemic immunosuppression in MAR, although results from 1 case should be generalized with abundant caution.
PMID: 30896772 [PubMed - as supplied by publisher]
Adjuvant systemic therapy in high-risk melanoma.
Melanoma Res. 2019 Mar 20;:
Authors: Blankenstein SA, van Akkooi ACJ
In resected high-risk melanoma (stage IIB/C-III) the risk of locoregional and/or distant recurrence is substantial and so far adjuvant therapies have been fairly unsuccessful. Interferon showed slight improvements in recurrence-free survival (RFS) but failed to convincingly improve overall survival (OS). In these patients, adjuvant therapy with treatments that show promising results in stage IV disease is arising. Studies using immune checkpoint blockade with anti-CTLA-4 and anti-PD-1 agents reveal convincing RFS benefits. OS rates, however, are not mature yet in most studies. Only ipilimumab has shown an OS benefit but at a high cost of toxicity. Also in studies with adjuvant targeted therapy using BRAF and MEK inhibitors, ensuring results are reported regarding RFS. As possible toxicity cannot be ignored, it is crucial to identify patients who would benefit most from these adjuvant therapies. In patients with clinically detectable lymph node metastases, studies using neoadjuvant schedules of immunotherapy and targeted therapy have been performed. In phase I and II studies the most optimal schedule of combination immunotherapy was identified and further research on this front will follow in the coming years. Concluding, after decades of scarce options for patients with high-risk melanoma, recent developments in adjuvant therapy have changed the standard of care for these patients.
PMID: 30896556 [PubMed - as supplied by publisher]