Melanoma Management最新文献

Due to the unique side-effect profile of immune checkpoint inhibitors (ICIs), groups of patients deemed to be at high risk of complications were excluded from trials that proved the efficacy and safety of these agents in patients with various malignancies. Among these excluded patients were those with prior solid organ transplantation, chronic viral infections and pre-existing autoimmune diseases including paraneoplastic syndromes. We present follow-up on a patient from a previously published case report with an orthotopic heart transplantation who was treated with both cytotoxic T-lymphocyte antigen 4 and PD-1 inhibition safely, without organ rejection. Additionally, we describe the case of a patient with a cardiac allograft who also did not experience organ rejection after treatment with pembrolizumab. Through smaller trials, retrospective analyses, case series and individual case reports, we are accumulating initial data on how these agents are tolerated by the aforementioned groups. Our survey of the literature has found more evidence of organ transplant rejection in patients treated with PD-1 inhibitors than those treated with inhibitors of cytotoxic T-lymphocyte antigen 4. Patients with chronic viral infections, especially hepatitis C, seem to have little to no risk of treatment-related increase in serum RNA levels. The literature contains few documented cases of devastating exacerbations of pre-existing autoimmune disease during treatment with ICIs, and flares seem to be easily controlled by immunosuppression in the vast majority of cases. Last, several cases allude to a promising role for disease-specific antibodies and other serum biomarkers in identifying patients at high risk of developing certain immune-related adverse events, detecting subclinical immune-related adverse event onset, and monitoring treatment response to immunosuppressive therapy in patients treated with ICIs. Though these excluded populations have not been well studied in randomized placebo-controlled trials, we may be able to learn and derive hypotheses from the existing observational data in the literature.

Mucosal melanomas are a rare subtype of melanoma and are associated with a particularly poor prognosis. Due to the rarity of the diagnosis, and the pace with which the management of cutaneous melanoma has evolved over recent years, there is little good evidence to guide management and evidence-based clinical guidelines are still in development in the UK. In this review we provide an overview of the management of mucosal melanoma, highlighting the critical differences between cutaneous and mucosal melanomas, before examining recent advances in the systemic treatment of this disease and likely future directions.

The contribution of nuclear medicine to management of melanoma patients is increasing. In intermediate-thickness N0 melanomas, lymphoscintigraphy provides a roadmap for sentinel node biopsy. With the introduction of single-photon emission computed tomography images with integrated computed tomography (SPECT/CT), 3D anatomic environments for accurate surgical planning are now possible. Sentinel node identification in intricate anatomical areas (pelvic cavity, head/neck) has been improved using hybrid radioactive/fluorescent tracers, preoperative lymphoscintigraphy and SPECT/CT together with modern intraoperative portable imaging technologies for surgical navigation (free-hand SPECT, portable gamma cameras). Furthermore, PET/CT today provides 3D roadmaps to resect ¹⁸F-fluorodeoxyglucose-avid melanoma lesions. Simultaneously, in advanced-stage melanoma and recurrences, ¹⁸F-fluorodeoxyglucose-PET/CT is useful in clinical staging and treatment decision as well as in the evaluation of therapy response. In this article, we review new insights and recent nuclear medicine advances in the management of melanoma patients.

The incidence of metastatic melanoma has been increasing dramatically over the last decades. Yet, there have been many new innovative therapies, such as targeted therapies and checkpoint inhibitors, which have made progress in survival for these patients. The oncology pharmacist is part of the healthcare team and can help in optimizing these newer therapies. There will be discussion about combination therapies, the oncology pharmacist's role, and issues at the core of his interest, such as drug interactions and complementary and alternative therapies.

Aim: Neoadjuvant treatment of locally advanced disease with BRAF inhibitors is expected to increase the likelihood of a R0 resection. We present six patients with stage III unresectable melanoma, neoadjuvantly treated with BRAF inhibitors.

Methods: Patients with unresectable, BRAF-mutated, stage III melanoma, were treated with BRAF inhibitors between 2012 and 2015. Unresectability was determined based on clinical and/or radiological findings. At maximal response, resection was performed. The specimen was reviewed to determine the degree of response.

Results: In five of six patients a radical resection was achieved. Postoperative complications were unremarkable. In five of six resected specimens, vital tumor tissue was found.

Conclusion: Neoadjuvant BRAF inhibitor treatment of locally advanced melanoma is feasible and has the potential to facilitate an R0 resection.

In vivo reflectance confocal microscopy (RCM) is a noninvasive high-resolution skin imaging tool that has become an important adjunct to clinical exam, dermoscopy and histopathology assessment, in the diagnosis and management of melanoma. RCM generates a horizontal view of the skin, whereby cellular and subcellular (e.g., nuclei, melanophages, collagen) structures, to the level of the upper dermis, are projected onto a screen at near-histological resolution. Morphologic descriptors, standardized terminology, and diagnostic algorithms are well established for the RCM assessment of melanoma, melanocytic, and nonmelanocytic lesions. Clinical applications of RCM in melanoma are broad and include diagnosis, assessment of large lesions on cosmetically sensitive areas, directing areas to biopsy, delineating margins prior to surgery, detecting response to treatment and assessing recurrence. This review will provide an overview of RCM technology, findings by melanoma subtype, clinical applications, as well as explore the accuracy of RCM for melanoma diagnosis, pitfalls and emerging uses of this technology ex vivo.

Aim: We aimed to characterize the safety profile of pembrolizumab in advanced melanoma patients at our center to better reflect 'real-world' data on anti-PD-1 inhibitors.

Materials & methods: At our institution, 58 ipilimumab-naive and 30 ipilimumab-treated patients with advanced melanoma who have received pembrolizumab between June 2014 and June 2017 were included for analysis.

Results: Incidence of any-grade and grade 3/4 toxicities were 81.8% (n = 72) and 12.5% (n = 11), respectively. The most common side effects were skin-related (61.4%, n = 54) and gastrointestinal-related (51.1%, n = 45) events. In total, 25% of patients required oral steroids to manage immune-related adverse events with a median cumulative prednisolone dose of 683 mg (range: 40-3745 mg).

Conclusion: Pembrolizumab is well tolerated in 'real-world' patients and severe toxicities can be effectively managed with systemic steroids.

Aim: We assessed the role of adjuvant interferon on relapse-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) in node-positive melanoma patients.

Methods: We retrospectively reviewed 385 node-positive patients without distant metastatic disease treated from 1998 to 2015. The surgery was therapeutic lymph node dissection (LND, n = 86) or sentinel lymph node biopsy ± completion LND (n = 270). 128 patients (33.2%) received adjuvant interferon.

Results: After a median follow-up of 70 months, interferon was associated with improved RFS (hazard ratio [HR]: 0.55; p < 0.001), DMFS (HR: 0.59; p < 0.001) and OS (HR: 0.61; p = 0.003), controlling for tumor and nodal stage, node size, sex, primary site, adjuvant therapy and extracapsular extension. In an exploratory age-matched comparison of patients treated with (n = 67) and without (n = 233) adjuvant immunotherapy, interferon still showed improved RFS, DMFS and OS.

Conclusion: Adjuvant interferon appears to improve OS among node-positive melanoma patients in a modern experience, providing context for comparison in the adjuvant therapy landscape.