Melanoma Management最新文献

{"title":"Systemic therapies for unresectable locoregional melanoma: a significant area of need","authors":"E. Nan Tie, J. Lai-Kwon, D. Gyorki","doi":"10.2217/mmt-2019-0010","DOIUrl":"https://doi.org/10.2217/mmt-2019-0010","url":null,"abstract":"Immune checkpoint inhibitors and BRAF-MEK inhibitors have revolutionized the management and prognosis of patients with metastatic melanoma. However, there is minimal evidence to guide their incorporation into current treatment paradigms for unresectable stage III disease. The era of effective systemic therapies has prompted a discussion about what constitutes unresectable disease. Patients with unresectable stage III disease can experience significant morbidity from their disease and locoregional therapies, and may progress with distant metastases. Despite increasing use of systemic therapies in unresectable stage III disease, further evidence is needed to establish their degree of benefit in this population.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41836644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Journal Watch: our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of melanoma management.","authors":"Robert V Rawson, Teresa Bailey, Andrew J Colebatch, Peter Ferguson","doi":"10.2217/mmt-2019-0002","DOIUrl":"https://doi.org/10.2217/mmt-2019-0002","url":null,"abstract":"Hauschild A, Dummer R, Schadendorf D et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant Stage III melanoma. J. Clin. Oncol. 36(35), 3441–3449 (2018) This publication, an update of the COMBI-AD trial, provides the most mature data with extended follow-up in Stage III metastatic melanoma patients treated with immune checkpoint or targeted therapies in the adjuvant setting. The results of this study of Stage III BRAF V600 mutant metastatic melanoma continue to show relapse-free survival (RFS) benefit at 40 months of dabrafenib plus trametinib therapy over placebo with an absolute difference of almost 20% between the arms. The RFS benefit was also confirmed regardless of stage, clinical and pathological subgroups. For the first time, the somewhat controversial, Weibull mixture cure-rate analysis has been used in metastatic melanoma patients and showed estimated cure rates of 54% (treatment arm) versus 37% (placebo arm). Moving forward it will be interesting to compare these results with the results of immunotherapy and combinations therapy trials in the adjuvant and neoadjuvant setting to ascertain the optimal treatment protocol for BRAF-mutant metastatic melanoma patients. – Written by Robert V Rawson","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 1","pages":"MMT18"},"PeriodicalIF":3.6,"publicationDate":"2019-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37358792","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 for melanoma in clinical practice in the United States (COSMUS-1)","authors":"M. Perez, J. Zager, T. Amatruda, R. Conry, C. Ariyan, Anupam M. Desai, J. Kirkwood, S. Treichel, D. Cohan, L. Raskin","doi":"10.2217/mmt-2019-0012","DOIUrl":"https://doi.org/10.2217/mmt-2019-0012","url":null,"abstract":"Aim: Talimogene laherparepvec (T-VEC) is an intralesional treatment for unresectable cutaneous, subcutaneous and nodal melanoma. COSMUS-1 was conducted to examine how T-VEC is used in US clinical practice. Materials & methods: A chart review was conducted at seven centers, with 78 patients screened and 76 eligible. Results: Patients began treatment with T-VEC between October 2015 and December 2016. Median follow-up was 9.4 months. Twenty percent of patients (n = 15) completed T-VEC treatment with no remaining injectable lesions or pathologic complete response. Flu-like symptoms were the most commonly reported adverse events (n = 8; 10.5%), followed by lesion ulceration (n = 4; 5.3%). No herpetic lesions or infections were reported. Conclusion: T-VEC was well tolerated and showed clinical utility.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49513528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neurotoxic effects of immune checkpoint inhibitor therapy for melanoma.","authors":"Lavinia Spain,&nbsp;Rachel Wong","doi":"10.2217/mmt-2019-0001","DOIUrl":"https://doi.org/10.2217/mmt-2019-0001","url":null,"abstract":"The advent of immune checkpoint inhibitors (ICIs), CTLA-4, PD-1 and PD-L1 inhibitors, have dramatically changed outcomes for patients with melanoma and other malignancies [1–3]. With this new class of antineoplastic agents comes a new range of adverse effects. These immune-related adverse events (irAEs) mediated by Tlymphocytes and other mechanisms including enhanced cytokine levels and antibodies [4] are often unpredictable, in contrast to adverse effects seen commonly with cytotoxic chemotherapy. Few of the initial Phase III trials evaluating the role of ICIs in the treatment of melanoma specifically reported immune-related neurotoxicity. When reported, the incidence of grade 3/4 neurotoxicity was low (<2%) [5]. Increasingly, immune-mediated neurological irAEs are being recognized and reported. Clinical presentation is varied and, while usually occurs early on in the course of therapy, in some cases neurological irAEs may occur many months after cessation of ICI therapy [6,7]. Importantly, the morbidity and mortality associated with this toxicity is relatively high. In a series of 613 fatal ICI-associated toxic events reported by Wang et al., 11% of these were attributed to neurological irAEs [8]. A review by Cuzzubbo et al. of neurological irAEs suggests that their incidence is higher with combination CTLA-4/PD-1 inhibition than for either class of agent when used as monotherapy. Interestingly, for monotherapy regimens, the reported rates of any grade neurotoxicity were higher for PD-1 inhibitors compared with CTLA4 inhibitors (anti-CTLA-4 3.8%, anti-PD-1 6.1%, combination therapy 13%). Severe (Grade 3 or 4) irAEs were infrequent, but more common with anti-CTLA-4 (0.7%) than anti-PD1 agents (0.4%). The majority of cases presented early with a median time to onset of 6 weeks [9]. These data are supported by other ‘real-world’ single-center retrospective series of patients treated with anti-CTLA-4 and/or anti-PD1 inhibitors [6] or anti-PD-1 inhibitors alone [10], reporting rates of neurological irAEs of 2.8 and 2.9%, respectively. In the former series, 14% of patients receiving combination therapy had neurological irAEs. In all three series, the clinical presentations were varied, highlighting the need for clinical vigilance when assessing patients for suspected irAEs.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 2","pages":"MMT16"},"PeriodicalIF":3.6,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215436","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":"Patient-specific dendritic cell vaccines with autologous tumor antigens in 72 patients with metastatic melanoma","authors":"R. Dillman, A. Cornforth, E. McClay, C. Depriest","doi":"10.2217/mmt-2018-0010","DOIUrl":"https://doi.org/10.2217/mmt-2018-0010","url":null,"abstract":"Aim: Metastatic melanoma patients were treated with patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines. Patients & methods: A total of 72 patients were enrolled in a single-arm Phase I/II (NCT00948480) trial or a randomized Phase II (NCT00436930). Results: Toxicity was minimal. Median overall survival (OS) was 49.4 months; 5-year OS 46%. A 5-year OS was 72% for 18 recurrent stage 3 without measurable disease when treated and 53% for 30 stage 4 without measurable disease when treated. A total of 24 patients with measurable stage 4 when treated (median of four prior therapies) had an 18.5 months median OS and 46% 2-year OS. Conclusion: This dendritic cell vaccine was associated with encouraging survival in all three clinical subsets. Clinicaltrial.gov NCT00436930 and NCT00948480.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2018-0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48548522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-biopsy of partially sampled thin melanoma impacts sentinel lymph node sampling as well as surgical margins.","authors":"Evan S Weitman,&nbsp;Matthew C Perez,&nbsp;Daniel Lee,&nbsp;Youngchul Kim,&nbsp;William Fulp,&nbsp;Vernon K Sondak,&nbsp;Amod A Sarnaik,&nbsp;Ricardo J Gonzalez,&nbsp;Carl W Cruse,&nbsp;Jane L Messina,&nbsp;Jonathan S Zager","doi":"10.2217/mmt-2018-0011","DOIUrl":"https://doi.org/10.2217/mmt-2018-0011","url":null,"abstract":"<p><strong>Aim: </strong>To assess the impact of re-biopsy on partially sampled melanoma <i>in situ</i> (MIS), atypical melanocytic proliferation (AMP) and thin invasive melanoma.</p><p><strong>Materials & methods: </strong>We retrospectively identified cases of re-biopsied partially sampled neoplasms initially diagnosed as melanoma <i>in situ</i>, AMP or thin melanoma (Breslow depth ≤0.75 mm).</p><p><strong>Results & conclusion: </strong>Re-biopsy led to sentinel lymph node biopsy (SLNB) in 18.3% of cases. No patients upstaged from AMP or MIS had a positive SLNB. One out of nine (11.1%) initially diagnosed as a thin melanoma ≤0.75 mm, upstaged with a re-biopsy, had a positive SLNB. After re-biopsy 8.5% underwent an increased surgical margin. Selective re-biopsy of partially sampled melanoma with gross residual disease can increase the accuracy of microstaging and optimize treatment regarding surgical margins and SLNB.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 2","pages":"MMT17"},"PeriodicalIF":3.6,"publicationDate":"2019-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2018-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215435","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":"Application of CO₂ laser evaporation in locally advanced melanoma.","authors":"Otis M Vrielink,&nbsp;Schelto Kruijff,&nbsp;Barbara L van Leeuwen,&nbsp;Jan Ln Roodenburg","doi":"10.2217/mmt-2018-0008","DOIUrl":"https://doi.org/10.2217/mmt-2018-0008","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to investigate the role of CO₂ laser evaporation in the treatment of melanoma patients with satellite or in-transit metastases.</p><p><strong>Materials & methods: </strong>Patients who underwent CO₂ laser evaporation were retrospectively included between November 2002 and August 2018. The Sharplan 40C CO₂ laser was used with a high pulse wave mode. Data concerning patient and tumor characteristics, CO₂ laser evaporation and subsequent therapies were collected.</p><p><strong>Results: </strong>A total of 26 patients were included. Median duration of local control was 5.5 months. The median number of lesions evaporated per treatment was three (1-16); patients received a median of three (1-19) treatments.</p><p><strong>Conclusion: </strong>In a selected group of melanoma patients with satellite or in-transit metastases, CO₂ laser evaporation should be considered as treatment for local control.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 1","pages":"MMT14"},"PeriodicalIF":3.6,"publicationDate":"2019-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2018-0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37358791","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":"Surveillance imaging for metastasis in high-risk melanoma: importance in individualized patient care and survivorship.","authors":"Morganna Freeman, Shachar Laks","doi":"10.2217/mmt-2019-0003","DOIUrl":"10.2217/mmt-2019-0003","url":null,"abstract":"<p><p>Most patients newly diagnosed with melanoma have early-stage disease considered of good prognosis. However, with a risk of recurrence, appropriate follow-up may include surveillance imaging for early relapse detection. Previously, surveillance imaging to detect recurrences was considered unjustified, given the lack of effective treatments. Now, systemic therapies have improved, and patients with low tumor burden may derive benefit from surveillance imaging. Despite this, controversy exists regarding the role of surveillance imaging in early-stage melanoma survivorship, in part reflected by the lack of consensus on specific imaging protocols and broad guidelines. This review discusses published evidence on surveillance imaging to detect metastasis in high-risk melanoma, the need for early recurrence detection and implications for value-based clinical decision-making, survivorship care and multidisciplinary patient management.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 1","pages":"MMT12"},"PeriodicalIF":1.0,"publicationDate":"2019-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/93/mmt-06-12.PMC6582455.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37358789","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":"Hypophysitis induced by immune checkpoint inhibitors in a Scottish melanoma population.","authors":"Khor Zhong Wei,&nbsp;Mark Baxter,&nbsp;Richard Casasola","doi":"10.2217/mmt-2018-0009","DOIUrl":"https://doi.org/10.2217/mmt-2018-0009","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to determine the incidence of all immune-mediated adverse events (IMAEs) with a focus on hypophysitis in patients with metastatic melanoma receiving immune checkpoint inhibitors (ICI).</p><p><strong>Methods: </strong>51 patients with metastatic melanoma who received immune checkpoint inhibitors (ipilimumab, pembrolizumab and nivolumab) in Ninewells Hospital, Dundee between 2014 and 2018 were identified. Patient demographic data and outcomes were recorded retrospectively.</p><p><strong>Results: </strong>A total of 6 patients (11.7%) developed hypophysitis, while 15 patients (29.4%) developed IMAEs. A significant improvement in overall survival (p = 0.03) and progression-free survival (p = 0.041) was seen in patients who developed IMAEs compared with those who did not.</p><p><strong>Conclusion: </strong>This study demonstrates a high rate of hypophysitis in melanoma patients receiving ipilimumab. Careful monitoring of symptoms is crucial to detect and appropriately manage IMAEs.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 1","pages":"MMT13"},"PeriodicalIF":3.6,"publicationDate":"2019-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2018-0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37358790","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":"Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations.","authors":"Michael J Grant,&nbsp;Nicholas DeVito,&nbsp;April K S Salama","doi":"10.2217/mmt-2018-0004","DOIUrl":"https://doi.org/10.2217/mmt-2018-0004","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"5 4","pages":"MMT10"},"PeriodicalIF":3.6,"publicationDate":"2018-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2018-0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36703650","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}