Pub Date : 2025-01-01DOI: 10.1016/j.ejcskn.2025.100285
Sophia Kreft , Tommaso Bosetti , Rebecca Lee , Paul Lorigan
Immunotherapy has dramatically changed the outcome for patients with advanced melanoma, with significant improvements in overall survival and potential cure for some. The recent approval of nivolumab in combination with relatlimab (nivolumab-relatlimab) added a third immunotherapy option for first-line treatment for advanced melanoma. Nivolumab-relatlimab has shown greater efficacy compared to single-agent nivolumab and has fewer unacceptable side effects compared to the combination of ipilimumab and nivolumab (ipilimumab-nivolumab). However, the lack of both long-term follow-up data and direct comparison with ipilimumab-nivolumab raises uncertainty about where to position nivolumab-relatlimab in clinical practice. Since most patients who respond to combination ipilimumab-nivolumab also respond to nivolumab-relatlimab, and many to single-agent anti-programmed death-1 (PD-1) monotherapy, the challenge is to identify the subgroup of patients who need ipilimumab-nivolumab and would not achieve similar benefits from less toxic alternatives. This review discusses the available data on efficacy of the three approved first-line immunotherapies (single-agent anti-PD-1, nivolumab-relatlimab or ipilimumab-nivolumab) and their value in distinct population groups to help guide clinical decisions.
{"title":"Selecting first-line immunotherapy in advanced melanoma: Current evidence on efficacy across diverse patient populations","authors":"Sophia Kreft , Tommaso Bosetti , Rebecca Lee , Paul Lorigan","doi":"10.1016/j.ejcskn.2025.100285","DOIUrl":"10.1016/j.ejcskn.2025.100285","url":null,"abstract":"<div><div>Immunotherapy has dramatically changed the outcome for patients with advanced melanoma, with significant improvements in overall survival and potential cure for some. The recent approval of nivolumab in combination with relatlimab (nivolumab-relatlimab) added a third immunotherapy option for first-line treatment for advanced melanoma. Nivolumab-relatlimab has shown greater efficacy compared to single-agent nivolumab and has fewer unacceptable side effects compared to the combination of ipilimumab and nivolumab (ipilimumab-nivolumab). However, the lack of both long-term follow-up data and direct comparison with ipilimumab-nivolumab raises uncertainty about where to position nivolumab-relatlimab in clinical practice. Since most patients who respond to combination ipilimumab-nivolumab also respond to nivolumab-relatlimab, and many to single-agent anti-programmed death-1 (PD-1) monotherapy, the challenge is to identify the subgroup of patients who need ipilimumab-nivolumab and would not achieve similar benefits from less toxic alternatives. This review discusses the available data on efficacy of the three approved first-line immunotherapies (single-agent anti-PD-1, nivolumab-relatlimab or ipilimumab-nivolumab) and their value in distinct population groups to help guide clinical decisions.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143323472","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}
Significant advancements have been made in the treatment of cutaneous melanoma over the past decade, particularly with the effectiveness of immune checkpoint inhibitors (ICIs) in advanced and adjuvant stages. However, the efficacy of ICIs for non-Caucasian populations and the rare clinical subtypes acral melanoma (AM) and mucosal melanoma (MM), has gradually been recognized to be lower in the advanced setting than cutaneous melanoma, suggesting that the use of ICIs in treating AM and MM need careful consideration in terms of ethnic and disease-specific factors to optimize outcomes in the adjuvant and neoadjuvant setting. However, the efficacy of adjuvant and neoadjuvant ICIs for AM and MM remains unclear. Therefore, in this review, we discussed the latest study updates on adjuvant and neoadjuvant therapies for AM and MM, focusing on anti-PD-1 antibody-based therapies. Our findings revealed that the efficacy of adjuvant and neoadjuvant therapy with anti-programmed death-1 receptor (anti-PD-1) antibody-based therapies for cutaneous melanoma is promising; however, their effectiveness varies according to ethnicity and melanoma subtype. There are several ongoing clinical trials on adjuvant and neoadjuvant therapies targeting AM or MM, which will provide the future perspectives of the strategy in the adjuvant and neoadjuvant settings for these rare melanoma subtypes.
{"title":"Adjuvant and neoadjuvant immunotherapy for acral and mucosal melanoma","authors":"Takaya Komori , Shigeru Koizumi , Sadao Inoue , Maiko Yamaura , Yuri Murayama , Atsushi Otsuka , Yasuhiro Nakamura","doi":"10.1016/j.ejcskn.2024.100277","DOIUrl":"10.1016/j.ejcskn.2024.100277","url":null,"abstract":"<div><div>Significant advancements have been made in the treatment of cutaneous melanoma over the past decade, particularly with the effectiveness of immune checkpoint inhibitors (ICIs) in advanced and adjuvant stages. However, the efficacy of ICIs for non-Caucasian populations and the rare clinical subtypes acral melanoma (AM) and mucosal melanoma (MM), has gradually been recognized to be lower in the advanced setting than cutaneous melanoma, suggesting that the use of ICIs in treating AM and MM need careful consideration in terms of ethnic and disease-specific factors to optimize outcomes in the adjuvant and neoadjuvant setting. However, the efficacy of adjuvant and neoadjuvant ICIs for AM and MM remains unclear. Therefore, in this review, we discussed the latest study updates on adjuvant and neoadjuvant therapies for AM and MM, focusing on anti-PD-1 antibody-based therapies. Our findings revealed that the efficacy of adjuvant and neoadjuvant therapy with anti-programmed death-1 receptor (anti-PD-1) antibody-based therapies for cutaneous melanoma is promising; however, their effectiveness varies according to ethnicity and melanoma subtype. There are several ongoing clinical trials on adjuvant and neoadjuvant therapies targeting AM or MM, which will provide the future perspectives of the strategy in the adjuvant and neoadjuvant settings for these rare melanoma subtypes.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143183584","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}
Pub Date : 2025-01-01DOI: 10.1016/j.ejcskn.2024.100279
Tommaso Bosetti , Oliver John Kennedy , Rebecca Lee , Avinash Gupta , Patricio Serra , Nadia Ali , Avanti Andhale , Sophia Kreft , Paul Lorigan
Introduction
Checkpoint inhibitors (CPI) and targeted therapy (TT) have revolutionised the outcomes for melanoma. Other than the approval of pembrolizumab for resected stage IIB/IIC in February 2023, there were no changes in the Systemic Anti-Cancer Therapy (SACT) treatments available for melanoma in England between 2019 and 2023. The national SACT dataset provides an insight on systemic treatment use during this timeframe. The purpose of this study was to evaluate the patterns of use and costs of SACT for melanoma between 2019 and 2023.
Materials and Methods
Data on prescriptions of SACT for adjuvant and metastatic disease between April 2019 to March 2023 were obtained from the SACT dataset and joinpoint regression analyses were used to look for any trends and change in trends. The list prices reported on the British National Formulary (BNF) were used to model drug acquisition costs.
Results
Data were available from a total of 71 Hospital Trusts. There was a non significant increasing trend in the adjuvant prescriptions (semestral percentage change = 3.25, 95% confidence interval [CI] -2.15–8.96, p = 0.22) and a non significant negative trend in the metastatic prescriptions (semestral percentage change = -0.59, 95% CI -3.02–1.92, p = 0.64) from April 2019 to March 2023. The estimated costs for SACT in the same timeframe were approximately £ 1.2 billion. Despite an increase in the spending on adjuvant therapy, the total costs in the financial year 2022–2023 decreased compared to 2019–2020 due to a slight reduction in the spending on metastatic treatment.
Conclusions
The opposite trends seen for adjuvant and metastatic prescriptions are a potential indicator of the impact of adjuvant treatment on development of distant metastases.
{"title":"Patterns of systemic treatment for melanoma: An insight on trends and costs between 2019–2023 from the English systemic anti-cancer therapy national database","authors":"Tommaso Bosetti , Oliver John Kennedy , Rebecca Lee , Avinash Gupta , Patricio Serra , Nadia Ali , Avanti Andhale , Sophia Kreft , Paul Lorigan","doi":"10.1016/j.ejcskn.2024.100279","DOIUrl":"10.1016/j.ejcskn.2024.100279","url":null,"abstract":"<div><h3>Introduction</h3><div>Checkpoint inhibitors (CPI) and targeted therapy (TT) have revolutionised the outcomes for melanoma. Other than the approval of pembrolizumab for resected stage IIB/IIC in February 2023, there were no changes in the Systemic Anti-Cancer Therapy (SACT) treatments available for melanoma in England between 2019 and 2023. The national SACT dataset provides an insight on systemic treatment use during this timeframe. The purpose of this study was to evaluate the patterns of use and costs of SACT for melanoma between 2019 and 2023.</div></div><div><h3>Materials and Methods</h3><div>Data on prescriptions of SACT for adjuvant and metastatic disease between April 2019 to March 2023 were obtained from the SACT dataset and joinpoint regression analyses were used to look for any trends and change in trends. The list prices reported on the British National Formulary (BNF) were used to model drug acquisition costs.</div></div><div><h3>Results</h3><div>Data were available from a total of 71 Hospital Trusts. There was a non significant increasing trend in the adjuvant prescriptions (semestral percentage change = 3.25, 95% confidence interval [CI] -2.15–8.96, p = 0.22) and a non significant negative trend in the metastatic prescriptions (semestral percentage change = -0.59, 95% CI -3.02–1.92, p = 0.64) from April 2019 to March 2023. The estimated costs for SACT in the same timeframe were approximately £ 1.2 billion. Despite an increase in the spending on adjuvant therapy, the total costs in the financial year 2022–2023 decreased compared to 2019–2020 due to a slight reduction in the spending on metastatic treatment.</div></div><div><h3>Conclusions</h3><div>The opposite trends seen for adjuvant and metastatic prescriptions are a potential indicator of the impact of adjuvant treatment on development of distant metastases.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143183585","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}
Mycosis fungoides (MF) is the most common form of a rare cutaneous T-cell lymphoma, often present with patches or plaques on the skin and characterized of malignant T cell infiltration. Topical Chlormethine (CL) gel has been approved by EMA for treatment of adult patients with MF. In clinical practice, chlormethine (CL) gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions.
Objective
Increase knowledge, identify and discuss the use of CL gel on MF lesions in clinical practice with the aim of improving patients health-related quality of life (QoL).
Method
in the present study a modified Delphi methodology is used. A panel of 7 experts (the Scientific Board) was selected to identify 22 statements to be voted by the extended panel (28 expert Italian dermatologists or haematologists) and consensus was reached on most of the points discussed.
Results
In case of early stages of the disease, it was stated that although the use of CL gel is recommended in stages IA-IIA. The panel agreed in supporting the tolerability of CL gel in combination with other topical or systemic therapies, paying attention to the type of lesion treated (stage) and emphasizing the fact that it is a very useful treatment for persistent or refractory lesions. It was also stated by the panel that maintenance therapy after a partial response is suggested until complete remission. Finally, the experts unanimously support how CL gel is characterized by speed of action and flexibility in its application and also has safety features in cases of early and advanced lesions, giving to the patient an improvement of Quality of Life.
{"title":"Italian expert opinion on the treatment of mycosis fungoides with chlormethine gel: Results of a Delphi consensus","authors":"Silvia Alberti Violetti , Marco Ardigò , Raffaele Filotico , Pietro Quaglino , Alessandro Pileri , Nicola Pimpinelli , Pierluigi Zinzani","doi":"10.1016/j.ejcskn.2025.100280","DOIUrl":"10.1016/j.ejcskn.2025.100280","url":null,"abstract":"<div><h3>Background</h3><div>Mycosis fungoides (MF) is the most common form of a rare cutaneous T-cell lymphoma, often present with patches or plaques on the skin and characterized of malignant T cell infiltration. Topical Chlormethine (CL) gel has been approved by EMA for treatment of adult patients with MF. In clinical practice, chlormethine (CL) gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions.</div></div><div><h3>Objective</h3><div>Increase knowledge, identify and discuss the use of CL gel on MF lesions in clinical practice with the aim of improving patients health-related quality of life (QoL).</div></div><div><h3>Method</h3><div>in the present study a modified Delphi methodology is used. A panel of 7 experts (the Scientific Board) was selected to identify 22 statements to be voted by the extended panel (28 expert Italian dermatologists or haematologists) and consensus was reached on most of the points discussed.</div></div><div><h3>Results</h3><div>In case of early stages of the disease, it was stated that although the use of CL gel is recommended in stages IA-IIA. The panel agreed in supporting the tolerability of CL gel in combination with other topical or systemic therapies, paying attention to the type of lesion treated (stage) and emphasizing the fact that it is a very useful treatment for persistent or refractory lesions. It was also stated by the panel that maintenance therapy after a partial response is suggested until complete remission. Finally, the experts unanimously support how CL gel is characterized by speed of action and flexibility in its application and also has safety features in cases of early and advanced lesions, giving to the patient an improvement of Quality of Life.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143183583","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}
Pub Date : 2025-01-01DOI: 10.1016/j.ejcskn.2025.100281
M. Jevric , I. Salatic , D. Brasanac , K. Griewank , A. Hauschild , D. Schadendorf , M. Stojanovic Milosavljevic , J. Filipovic , M. Dencic-Fekete , V. Sondak , M. Zegarac , L. Kandolf
Congenital melanoma is a very rare condition defined as a melanoma recognized at or shortly after birth. It may arise de novo or from transplacental metastasis of maternal melanoma. In this case report, de novo primary congenital melanoma presented during the first four months of life, and was diagnosed by histopathological, immunohistochemical, FISH and genetic analysis. Re-excision and sentinel lymph node biopsy was performed, which revealed a micrometastasis in the sentinel lymph node. No adjuvant treatment was provided. There were no signs of relapse with 15 months postoperative follow-up.
{"title":"Neonatal melanoma with lymph node metastasis","authors":"M. Jevric , I. Salatic , D. Brasanac , K. Griewank , A. Hauschild , D. Schadendorf , M. Stojanovic Milosavljevic , J. Filipovic , M. Dencic-Fekete , V. Sondak , M. Zegarac , L. Kandolf","doi":"10.1016/j.ejcskn.2025.100281","DOIUrl":"10.1016/j.ejcskn.2025.100281","url":null,"abstract":"<div><div>Congenital melanoma is a very rare condition defined as a melanoma recognized at or shortly after birth. It may arise de novo or from transplacental metastasis of maternal melanoma. In this case report, de novo primary congenital melanoma presented during the first four months of life, and was diagnosed by histopathological, immunohistochemical, FISH and genetic analysis. Re-excision and sentinel lymph node biopsy was performed, which revealed a micrometastasis in the sentinel lymph node. No adjuvant treatment was provided. There were no signs of relapse with 15 months postoperative follow-up.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100281"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143183163","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}
To describe various clinical pictures of posterior scleritis following pembrolizumab therapy for metastatic cutaneous melanoma.
Methods
Description of the clinical case with data from patient presentation and recurrences, diagnostic examinations, treatment, and six-months follow up. Clinical presentation of previous reports of pembrolizumab related of eye inflammation are discussed.
Results
A 49-year-old patient underwent resection of metastatic melanoma of the skin with sentinel lymph nodes removal and pembrolizumab adjuvant therapy every three weeks. Nine months after pembrolizumab initiation the patient accessed ophthalmology emergency service complaining one week vision loss on her right eye associated with pain on eye movement. Ocular examination revealed right eye papillitis and posterior scleritis. Intravenous corticosteroid treatment was started associated with topical prednisolone drops, after which complete resolution of the subretinal fluid was seen. During the six months follow up one episode of posterior scleritis was observed in the contralateral eye and resolved after peribulbar corticosteroid injection and oral therapy and one recurrence of intermediate scleritis in the right eye which resolved after oral therapy.
Conclusion
Posterior and intermediate scleritis may be added to the spectrum of pembrolizumab related eye inflammation; in the case presented posterior scleritis occurred asymmetrically in both eyes suggesting chronic features, importance of steroid tapering and follow up.
{"title":"Diagnostic challenges of posterior scleritis in pembrolizumab treated patient for cutaneous melanoma: A case report","authors":"Fabrizio Sinisi , Cesare Pirondini , Emanuela Passoni , Cinzia Solinas , Ornella Garrone , Nerina Denaro","doi":"10.1016/j.ejcskn.2024.100019","DOIUrl":"https://doi.org/10.1016/j.ejcskn.2024.100019","url":null,"abstract":"<div><h3>Purpose</h3><p>To describe various clinical pictures of posterior scleritis following pembrolizumab therapy for metastatic cutaneous melanoma.</p></div><div><h3>Methods</h3><p>Description of the clinical case with data from patient presentation and recurrences, diagnostic examinations, treatment, and six-months follow up. Clinical presentation of previous reports of pembrolizumab related of eye inflammation are discussed.</p></div><div><h3>Results</h3><p>A 49-year-old patient underwent resection of metastatic melanoma of the skin with sentinel lymph nodes removal and pembrolizumab adjuvant therapy every three weeks. Nine months after pembrolizumab initiation the patient accessed ophthalmology emergency service complaining one week vision loss on her right eye associated with pain on eye movement. Ocular examination revealed right eye papillitis and posterior scleritis. Intravenous corticosteroid treatment was started associated with topical prednisolone drops, after which complete resolution of the subretinal fluid was seen. During the six months follow up one episode of posterior scleritis was observed in the contralateral eye and resolved after peribulbar corticosteroid injection and oral therapy and one recurrence of intermediate scleritis in the right eye which resolved after oral therapy.</p></div><div><h3>Conclusion</h3><p>Posterior and intermediate scleritis may be added to the spectrum of pembrolizumab related eye inflammation; in the case presented posterior scleritis occurred asymmetrically in both eyes suggesting chronic features, importance of steroid tapering and follow up.</p></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"2 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277261182400003X/pdfft?md5=d7018ba9d27498062baa3a2443ebce86&pid=1-s2.0-S277261182400003X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139504339","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}
Pub Date : 2024-01-15DOI: 10.1016/j.ejcskn.2024.100017
Charlie Yue Wang , Mark Shackleton , Sonia Mailer , Grant A. McArthur , Sophia Zoungas , Rory Wolfe , Victoria J. Mar
Background
Pre-clinical and clinical studies propose that statins may have chemopreventive effects against cancer, suggesting their possible roles as adjunctive therapies for melanoma.
Objective
To investigate the association between regular statin use and disease recurrence in patients with resected Stage I-III melanoma.
Methods
We conducted a retrospective analysis of patients enrolled in the multi-center Melanoma Research Victoria cohort with a histologically confirmed, resected American Joint Committee on Cancer Stage I-III cutaneous melanoma. Patients with uveal melanoma, melanoma of unknown primary site, or mucosal melanoma were excluded. Melanoma recurrence outcomes were compared between statin users and statin non-users, with statin use determined by linkage to the Pharmaceutical Benefits Scheme (Australia) prescription database.
Results
624 patients with resected Stage I-III melanoma at diagnosis were eligible for the study. 193 patients were classified as statin users and 431 patients as statin non-users. In all, 45 statin users experienced disease recurrence compared to 140 (23.3 vs 32.5%, p = 0.05) statin non-users with similar durations of follow-up (median 2.2 and 2.4 years, respectively). After adjustment, statin users had a lower risk melanoma recurrence than statin non-users (HR 0.66, 95%CI 0.44–0.99, p = 0.04). A lower risk of recurrence was also observed in subset analyzes of statin users on high-dose therapy (HR 0.50, 95%CI 0.25–0.99, p = 0.05) and patients who were adherent to statin therapy (HR 0.60, 95%CI 0.39–0.92, p = 0.02).
Conclusion
Our study supports the possibility that an association exists between statin use and reduced disease recurrence in resected cutaneous melanoma.
背景临床前和临床研究表明，他汀类药物可能具有化学预防癌症的作用，这表明它可以作为黑色素瘤的辅助疗法。方法我们对加入多中心维多利亚黑色素瘤研究队列、经组织学确诊并切除的美国癌症联合委员会I-III期皮肤黑色素瘤患者进行了回顾性分析。葡萄膜黑色素瘤、原发部位不明的黑色素瘤或粘膜黑色素瘤患者除外。比较了他汀类药物使用者和非他汀类药物使用者的黑色素瘤复发情况，他汀类药物的使用情况通过与澳大利亚药品福利计划处方数据库的链接来确定。193名患者被归类为他汀类药物使用者，431名患者被归类为他汀类药物非使用者。在相似的随访时间（中位数分别为2.2年和2.4年）内，45名他汀类药物使用者与140名他汀类药物非使用者（23.3% vs 32.5%，p = 0.05）相比出现了疾病复发。经调整后，他汀类药物使用者的黑色素瘤复发风险低于非他汀类药物使用者（HR 0.66，95%CI 0.44-0.99，p = 0.04）。结论：我们的研究证实，在切除的皮肤黑色素瘤中，他汀类药物的使用与疾病复发率的降低之间可能存在关联。
{"title":"Statin use in resected, high-risk cutaneous melanoma: A multi-centre retrospective cohort study","authors":"Charlie Yue Wang , Mark Shackleton , Sonia Mailer , Grant A. McArthur , Sophia Zoungas , Rory Wolfe , Victoria J. Mar","doi":"10.1016/j.ejcskn.2024.100017","DOIUrl":"https://doi.org/10.1016/j.ejcskn.2024.100017","url":null,"abstract":"<div><h3>Background</h3><p>Pre-clinical and clinical studies propose that statins may have chemopreventive effects against cancer, suggesting their possible roles as adjunctive therapies for melanoma.</p></div><div><h3>Objective</h3><p>To investigate the association between regular statin use and disease recurrence in patients with resected Stage I-III melanoma.</p></div><div><h3>Methods</h3><p>We conducted a retrospective analysis of patients enrolled in the multi-center Melanoma Research Victoria cohort with a histologically confirmed, resected American Joint Committee on Cancer Stage I-III cutaneous melanoma. Patients with uveal melanoma, melanoma of unknown primary site, or mucosal melanoma were excluded. Melanoma recurrence outcomes were compared between statin users and statin non-users, with statin use determined by linkage to the Pharmaceutical Benefits Scheme (Australia) prescription database.</p></div><div><h3>Results</h3><p>624 patients with resected Stage I-III melanoma at diagnosis were eligible for the study. 193 patients were classified as statin users and 431 patients as statin non-users. In all, 45 statin users experienced disease recurrence compared to 140 (23.3 vs 32.5%, p = 0.05) statin non-users with similar durations of follow-up (median 2.2 and 2.4 years, respectively). After adjustment, statin users had a lower risk melanoma recurrence than statin non-users (HR 0.66, 95%CI 0.44–0.99, p = 0.04). A lower risk of recurrence was also observed in subset analyzes of statin users on high-dose therapy (HR 0.50, 95%CI 0.25–0.99, p = 0.05) and patients who were adherent to statin therapy (HR 0.60, 95%CI 0.39–0.92, p = 0.02).</p></div><div><h3>Conclusion</h3><p>Our study supports the possibility that an association exists between statin use and reduced disease recurrence in resected cutaneous melanoma.</p></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"2 ","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772611824000016/pdfft?md5=6e345491703535cf350a71b46b8a151f&pid=1-s2.0-S2772611824000016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139493096","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}
Pub Date : 2024-01-01DOI: 10.1016/j.ejcskn.2024.100268
Jacques Pierre du Toit, Johann de Wet
{"title":"The “Lone Wolf” sign: An underutilised aid for the diagnosis of melanoma in patients lacking multiple nevi","authors":"Jacques Pierre du Toit, Johann de Wet","doi":"10.1016/j.ejcskn.2024.100268","DOIUrl":"10.1016/j.ejcskn.2024.100268","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"2 ","pages":"Article 100268"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423007","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}
Pub Date : 2024-01-01DOI: 10.1016/j.ejcskn.2024.100260
Marc Bender , I.-Peng Chen , Leonie Bluhm , Peter Mohr , Beate Volkmer , Rüdiger Greinert
Introduction
Cutaneous malignant melanoma suffers from the highest metastasis rate and mortality among different skin cancer entities. However, with emerging immune checkpoint inhibitor (ICI) therapy, prognosis has significantly improved over the last years. To better assess treatment response stable and reliable biomarkers are needed.
Methods
We gathered blood samples of 81 patients with predominantly AJCC Stage III/IV melanoma to evaluate serum markers and plasma-derived miRNAs. A machine learning model was developed to predict immunotherapy response. Serum markers were measured according to standard clinical routines. Expression levels of 61 miRNAs were quantified via flowcytometry. LASSO logistic regression was fit to the data to predict therapy outcome, employing AUROC as the performance metric. Nested cross-validation was used to mitigate overfitting.
Results
Plasma-derived miRNA expression exhibited significant association with therapy response for 5 miRNAs: miR-132–3p, miR-137, miR-197, miR-214, miR-514a-3p. Serum markers LDH, CRP, S100 and eosinophile concentration showed significant differences between Responders and Non-Responders. Age and previous anti-BRAF therapy (BRAFi/MEKi) were the only demographic parameters significantly related to therapy outcome. Among six machine learning models tested, a relaxed LASSO approach on the entire dataset performed best (AUC = 0.851).
Conclusion
Validation of the relaxed LASSO model in the outer loop of the nested cross validation yielded an AUC of 0.847. This model incorporated expression of a miRNA-quartet, LDH, patient age and prior BRAFi/MEKi. It effectively identifies Responders and Non-Responders with high sensitivity and specificity, presenting promising candidates for the validation of future biomarkers.
{"title":"LASSO logistic regression reveals a mixed MiRNA and serum-marker classifier for prediction of immunotherapy response in liquid biopsies of melanoma patients","authors":"Marc Bender , I.-Peng Chen , Leonie Bluhm , Peter Mohr , Beate Volkmer , Rüdiger Greinert","doi":"10.1016/j.ejcskn.2024.100260","DOIUrl":"10.1016/j.ejcskn.2024.100260","url":null,"abstract":"<div><h3>Introduction</h3><p>Cutaneous malignant melanoma suffers from the highest metastasis rate and mortality among different skin cancer entities. However, with emerging immune checkpoint inhibitor (ICI) therapy, prognosis has significantly improved over the last years. To better assess treatment response stable and reliable biomarkers are needed.</p></div><div><h3>Methods</h3><p>We gathered blood samples of 81 patients with predominantly AJCC Stage III/IV melanoma to evaluate serum markers and plasma-derived miRNAs. A machine learning model was developed to predict immunotherapy response. Serum markers were measured according to standard clinical routines. Expression levels of 61 miRNAs were quantified via flowcytometry. LASSO logistic regression was fit to the data to predict therapy outcome, employing AUROC as the performance metric. Nested cross-validation was used to mitigate overfitting.</p></div><div><h3>Results</h3><p>Plasma-derived miRNA expression exhibited significant association with therapy response for 5 miRNAs: miR-132–3p, miR-137, miR-197, miR-214, miR-514a-3p. Serum markers LDH, CRP, S100 and eosinophile concentration showed significant differences between Responders and Non-Responders. Age and previous anti-BRAF therapy (BRAFi/MEKi) were the only demographic parameters significantly related to therapy outcome. Among six machine learning models tested, a relaxed LASSO approach on the entire dataset performed best (AUC = 0.851).</p></div><div><h3>Conclusion</h3><p>Validation of the relaxed LASSO model in the outer loop of the nested cross validation yielded an AUC of 0.847. This model incorporated expression of a miRNA-quartet, LDH, patient age and prior BRAFi/MEKi. It effectively identifies Responders and Non-Responders with high sensitivity and specificity, presenting promising candidates for the validation of future biomarkers.</p></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"2 ","pages":"Article 100260"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772611824002489/pdfft?md5=bf70acd75897b7b894bf210588d1b406&pid=1-s2.0-S2772611824002489-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978468","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}
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