Melanoma Management最新文献

{"title":"Is the neutrophil-to-lymphocyte ratio a useful prognostic indicator in melanoma patients?","authors":"Joshua T Cohen, Thomas J Miner, Michael P Vezeridis","doi":"10.2217/mmt-2020-0006","DOIUrl":"10.2217/mmt-2020-0006","url":null,"abstract":"<p><p>The neutrophil-to-lymphocyte ratio (NLR) is gaining traction as a biomarker with utility in a variety of malignancies including melanoma. Intact lymphocyte function is necessary for tumor surveillance and destruction, and neutrophils play a role in suppressing lymphocyte proliferation and in the induction of lymphocyte apoptosis. Early research in melanoma indicates that in high-risk localized melanoma, a high NLR is correlated with worse overall and disease-free survival. Similarly, in metastatic melanoma treated with both metastasectomy and immunotherapies, an elevated NLR is predictive of shortened overall survival and progression-free survival. Future studies incorporating NLR into more traditional melanoma prognostic markers while employing more granular outcomes, are needed to realize the full potential of NLR.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2020-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/53/mmt-07-47.PMC7475797.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pandemic medicine: the management of advanced melanoma during COVID-19.","authors":"James R Patrinely,&nbsp;Douglas B Johnson","doi":"10.2217/mmt-2020-0012","DOIUrl":"https://doi.org/10.2217/mmt-2020-0012","url":null,"abstract":"Amid the COVID-19 pandemic cancer patients present a unique challenge, as they are often immunosuppressed or subject to treatment-related toxicities that may cause severe disease manifestations. The practical impact of the COVID-19 pandemic on the management of advanced melanoma warrants further consideration. Restrictions on the US healthcare system to mitigate COVID-19 transmission have significantly altered melanoma management practices from the initial diagnosis of primary cutaneous disease to systemic treatment for advanced and metastatic presentations. We herein report our experience and recommendations for this patient population, highlighting the importance patient-centered planning based on tumor characteristics, resource availability and the local state of COVID-19 control.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2020-0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylated circulating tumor DNA as a biomarker in cutaneous melanoma.","authors":"Russell J Diefenbach,&nbsp;Jenny H Lee,&nbsp;Helen Rizos","doi":"10.2217/mmt-2020-0010","DOIUrl":"https://doi.org/10.2217/mmt-2020-0010","url":null,"abstract":"The detection and monitoring of circulating tumor DNA (ctDNA) in melanoma using mutation-detection techniques such as droplet digital PCR and targeted next-generation sequencing (NGS) panels has been well documented (reviewed in [1]). In melanoma, baseline ctDNA assessment predicts overall survival of stage III patients and longitudinal assessment predicts response and survival of stage IV patients treated with immune checkpoint inhibitors and targeted therapies [2–4]. ctDNA can also be used to monitor the appearance of treatment-resistant melanoma subclones [2], tumor heterogeneity [5], metabolic tumor burden [6] and differentiates true progression from pseudoprogression in melanoma patients treated with immunotherapy [7]. ctDNA can be detected in approximately 34% of stage III melanoma and 73% of stage IV melanoma [2,4]. Several customized melanoma-associated NGS mutation panels for ctDNA have been described [8,9], and these panels are designed to detect greater than 80% of melanomas with mutant allele frequency detection limits of only 0.1%. These sequencing panels have several limitations, however. They often yield lower coverage of guaninecytosine (GC)-rich DNA regions, and these regions can be extremely informative cancer markers. For instance, the TERT gene has a GC-rich promoter that is mutated in approximately 70% of melanomas [8]. The complete sequencing of large genes (such as the NF1 gene at >8 kb) is also difficult as the increased gene coverage comes at the expense of overall mutation detection sensitivity. Moreover, the significance of many, low-frequency mutations can be unclear and alterations in some genes, including the TP53 tumor suppressor gene, may not reflect tumor biology, but rather clonal hematopoiesis, a common age-associated phenomenon involving the expansion of nucleated blood cells with somatic mutations [10]. An alternative liquid biopsy approach for monitoring cancer, without prior knowledge of somatic mutation profiles, involves the detection of epigenetic DNA changes, such as methylation. Methylation of cytosine residues within CpG islands is important for the regulation of gene expression and is altered during the development and progression of many cancers, including melanoma. Importantly, aberrant methylation of CpG-rich gene promoters can be a very consistent feature of cancer [11] and thus, the analysis of methylated DNA in liquid biopsies is a rapidly emerging area of interest [12]. Patterns of DNA methylation can change during melanoma progression and the analysis of DNA methylation can provide valuable information related to the phenotypic behavior and stage of melanoma [13]. The analysis of ctDNA methylation is challenging due to the low amounts and highly fragmented nature of ctDNA. Typically, most methylation analysis workflows incorporate an initial bisulfite conversion step which preserves methylated cytosines prior to downstream sequencing. With limited amounts of ctDNA, it is imperative that the ef","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2020-0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoma in pregnancy: certainties unborn.","authors":"Enrico Zelin, Claudio Conforti, Roberta Giuffrida, Teresa Deinlein, Nicola di Meo, Iris Zalaudek","doi":"10.2217/mmt-2020-0007","DOIUrl":"10.2217/mmt-2020-0007","url":null,"abstract":"<p><p>Melanoma diagnosed during childbearing period or up to 1 year after delivery is defined as pregnancy-associated melanoma (PAM). There is some evidence that PAM has worse prognosis if compared with melanoma in nonpregnant women, although literature is still inconclusive. Many biological mechanisms could explain this behavior, such as hormonal and immune status, increased lymphangiogenesis but also delay in diagnostic and therapeutic management. If PAM is suspected, a prompt excisional biopsy under local anesthesia can be performed regardless of the gestational period. Conversely, additional staging procedures (such as sentinel lymph node biopsy or imaging) and systemic therapy are still debatable during pregnancy. A multidisciplinary tailored approach should be preferred, together with exhaustive counseling of the mother.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/4f/mmt-07-48.PMC7475795.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on GM-CSF and its potential role in melanoma management.","authors":"Robert O Dillman","doi":"10.2217/mmt-2020-0011","DOIUrl":"https://doi.org/10.2217/mmt-2020-0011","url":null,"abstract":"<p><p>GM-CSF drives the differentiation of granulocytes and monocyte/macrophages from hematopoietic stem cell progenitors. It is required for differentiating monocytes into dendritic cells (DC). Although approved for recovery of granulocytes/monocytes in patients receiving chemotherapy, G-CSF is preferred. Enthusiasm for GM-CSF monotherapy as a melanoma treatment was dampened by two large randomized trials. Although GM-CSF has been injected into tumors for many years, the efficacy of this has not been tested. There is a strong rationale for GM-CSF as a vaccine adjuvant, but it appears of benefit only for strategies that directly involve DCs, such as intratumor talimogene laherparepvec and vaccines in which DCs are loaded with antigen <i>ex vivo</i> and injected admixed with GM-CSF.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2020-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laparoscopically assisted ilio-inguinal lymph node dissection versus inguinal lymph node dissection in melanoma.","authors":"Enrique Boldo,&nbsp;Araceli Mayol,&nbsp;Rafael Lozoya,&nbsp;Alba Coret,&nbsp;Diana Escribano,&nbsp;Carlos Fortea,&nbsp;Andres Muñoz,&nbsp;Juan Carlos Pastor,&nbsp;Guillermo Perez De Lucia","doi":"10.2217/mmt-2019-0023","DOIUrl":"https://doi.org/10.2217/mmt-2019-0023","url":null,"abstract":"<p><strong>Aim: </strong>Morbidity of open inguinal lymphadenectomy (OIL) is high. We use laparoscopy for pelvic time, preservation of the greater saphenous vein and transverse inguinal incisions (laparoscopically assisted ilio-inguinal lymphadenectomy, LIIL) to improve postoperative outcomes.</p><p><strong>Patients & methods: </strong>Retrospective comparison of 14 patients who underwent LIIL and seven patients who underwent OIL.</p><p><strong>Results: </strong>Fourteen LIIL compared with seven OIL showed a statistically significant reduction in morbidity (15.3 vs 75%) and hospital stay (7 vs 15.7 days). Pelvic lymph node involvement (27%) was not detected preoperatively. With a mean follow-up of 36.2 (range: 3-137) months, local recurrence rate was 58.3% in LIIL and 40% in OIL. Overall survival was significantly higher in OIL than in LIIL.</p><p><strong>Conclusion: </strong>Compared with OIL, LIIL reduced postoperative complications and hospital stay.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38294802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary cilia: putting a sensor on the underlying melanocytic tumor cell state.","authors":"Ursula E Lang","doi":"10.2217/mmt-2020-0008","DOIUrl":"https://doi.org/10.2217/mmt-2020-0008","url":null,"abstract":"Melanocytic neoplasms constitute some of the most challenging histopathologic entities in pathology and trigger high levels of diagnostic uncertainty among general practice pathologists and even among expert dermatopathologists [1,2]. When histopathologic findings are ambiguous or indeterminate, one turns to immunohistochemical and/or genetic analyses, given sufficient tissue and resources [3]. These additional tests can provide valuable information about the underlying genetic drivers, level of genomic instability and relative levels of key transcripts, which are then integrated with histopathology and clinical information [4]. When fortunate enough to obtain the genetic data, the hope is for a compelling basis to definitively classify the tumor. Analysis may be less than straightforward, as mutations or chromosomal changes of unknown significance may be uncovered. Additional impediments to diagnosis include poor quality DNA, low purity of tumor cells and a chromosomal copy-number neutral melanoma. For these reasons, the gold standard remains histopathologic review by an experienced dermatopathologist. Often the true malignant potential remains a mystery, and management is aimed at balancing caution with morbidity. In such instances, one can wonder if microRNA (miRNA), transcriptomic or DNA methylation data would shed more light onto the underlying biologic potential [5–7]. In the case of miRNAs, which are stable in formalin-fixed paraffin-embedded (FFPE) tissue, several studies have shown the potential for use as diagnostic biomarkers [6,8]. Although mRNA is less stable than miRNAs in FFPE, commercially available kits leverage a limited panel of gene transcripts that can predict risk of recurrence, metastasis and assist in diagnosis [9]. DNA methylation shares the advantage of stability similar to miRNAs, and appears to correlate with poor prognosis in advanced melanoma [5]. The epigenetic information gained from methylation analysis remains unknown in histopathologically indeterminate lesions. Challenges in using these tests include the lack of high-quality evidence guiding best practice use [10]. As any cell biologist will attest, it is the proteome and interactome of cells that ultimately results in behavior. While the complexity can be overwhelming, it remains a fascination and continues to propel the field of melanoma biology. It is in this vein that the assessment of primary cilia has emerged as a window into melanoma cell biology. The primary cilium is ubiquitous cell surface organelle that acts as cellular antenna, sensing the extracellular environment and transmitting downstream signals [11]. Many important signaling pathways have been linked to the primary cilium in a cell-context-dependent manner and implicated in cancer pathogenesis [12]. With respect to melanocytes and melanoma progression, there are limited but intriguing data to support the WNT/β-catenin pathway being repressed by an intact primary cilium [13]. Additionally, the ","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2020-0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38294800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparity in outcomes of melanoma adjuvant immunotherapy by demographic profile.","authors":"Alexandra Ikeguchi,&nbsp;Michael Machiorlatti,&nbsp;Sara K Vesely","doi":"10.2217/mmt-2020-0002","DOIUrl":"https://doi.org/10.2217/mmt-2020-0002","url":null,"abstract":"<p><strong>Background: </strong>Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors.</p><p><strong>Materials & methods: </strong>We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan-Meier method and Cox proportional hazards models.</p><p><strong>Results: </strong>All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy.</p><p><strong>Conclusion: </strong>Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2020-0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38286648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Observational study of talimogene laherparepvec use in the anti-PD-1 era for melanoma in the US (COSMUS-2).","authors":"James Sun, Brian R Gastman, Lucy McCahon, Elizabeth I Buchbinder, Igor Puzanov, Michele Nanni, James M Lewis, Richard D Carvajal, Shahnaz Singh-Kandah, Anupam M Desai, Leon Raskin, Carrie M Nielson, Rubina Ismail, Jonathan S Zager","doi":"10.2217/mmt-2020-0005","DOIUrl":"10.2217/mmt-2020-0005","url":null,"abstract":"<p><strong>Aim: </strong>Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization.</p><p><strong>Materials & methods: </strong>A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions.</p><p><strong>Results: </strong>Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable lesions, 37% discontinued T-VEC due to progressive disease. Discontinuation of T-VEC did not differ by anti-PD-1-based therapy use or timing.</p><p><strong>Conclusion: </strong>In real-world settings, T-VEC may be used concurrently with or after anti-PD-1-based therapy.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/5e/mmt-07-41.PMC7426742.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38294801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoma brain metastases: review of histopathological features and immune-molecular aspects.","authors":"Lorenzo Salvati,&nbsp;Mario Mandalà,&nbsp;Daniela Massi","doi":"10.2217/mmt-2019-0021","DOIUrl":"https://doi.org/10.2217/mmt-2019-0021","url":null,"abstract":"<p><p>Patients with melanoma brain metastases (MBM) have a dismal prognosis, but the unprecedented advances in systemic therapy alone or in combination with local therapy have now extended the 1-year overall survival rate from 20-25% to nearing 80-85%, mainly in asymptomatic patients. The histopathological and molecular characterization of MBM and the understanding of the microenvironment are critical to more effectively manage patients with advanced melanoma and to design biologically driven clinical trials. This review aims to give an overview of the main histopathological features and the immune-molecular aspects of MBM.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2020-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38286649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}