Pub Date : 2024-02-01Epub Date: 2023-11-28DOI: 10.1097/CMR.0000000000000928
Rui Duarte, Filipa Trigo, Ivan Luz, Paulo Santos
Immune checkpoint inhibitors are effective monoclonal antibodies used in cancer treatment, particularly in metastatic melanoma. They target proteins responsible for cancer cells evading the immune system. However, their use can lead to immune-related adverse events, with the skin and gastrointestinal tract being commonly affected. Kidney involvement is rarer, with interstitial nephritis being the most common manifestation. In a unique case, kidney biopsy-proven small-vessel vasculitis with arteriolar immune deposition was observed following ipilimumab administration.
{"title":"Small-vessel vasculitis leading to severe acute kidney injury after ipilimumab: a case report.","authors":"Rui Duarte, Filipa Trigo, Ivan Luz, Paulo Santos","doi":"10.1097/CMR.0000000000000928","DOIUrl":"10.1097/CMR.0000000000000928","url":null,"abstract":"<p><p>Immune checkpoint inhibitors are effective monoclonal antibodies used in cancer treatment, particularly in metastatic melanoma. They target proteins responsible for cancer cells evading the immune system. However, their use can lead to immune-related adverse events, with the skin and gastrointestinal tract being commonly affected. Kidney involvement is rarer, with interstitial nephritis being the most common manifestation. In a unique case, kidney biopsy-proven small-vessel vasculitis with arteriolar immune deposition was observed following ipilimumab administration.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"76-79"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-19DOI: 10.1097/CMR.0000000000000941
Katie Roster, Christopher Thang, Sumaiya Islam, Shari R Lipner
{"title":"Underreporting of acral lentiginous melanoma in studies informing American Joint Committee on Cancer Staging System Guidelines: a review of 150 cited studies.","authors":"Katie Roster, Christopher Thang, Sumaiya Islam, Shari R Lipner","doi":"10.1097/CMR.0000000000000941","DOIUrl":"10.1097/CMR.0000000000000941","url":null,"abstract":"","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"34 1","pages":"84-88"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-11-13DOI: 10.1097/CMR.0000000000000935
Noémi E Mezőlaki, Eszter Baltás, Henriette L Ócsai, Anita Varga, Irma Korom, Erika Varga, István B Németh, Erika G Kis, János Varga, Ádám Kocsis, Rolland Gyulai, Mátyás Bukva, Lajos Kemény, Judit Oláh
We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan-Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1-T4) of the primary tumour. Regression was significantly positively related to PFS ( P = 0.0018, HR = 0.352) and OS ( P = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P = 0.0001, HR = 2.629; OS: P = 0.0003, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.
{"title":"Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study.","authors":"Noémi E Mezőlaki, Eszter Baltás, Henriette L Ócsai, Anita Varga, Irma Korom, Erika Varga, István B Németh, Erika G Kis, János Varga, Ádám Kocsis, Rolland Gyulai, Mátyás Bukva, Lajos Kemény, Judit Oláh","doi":"10.1097/CMR.0000000000000935","DOIUrl":"10.1097/CMR.0000000000000935","url":null,"abstract":"<p><p>We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan-Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1-T4) of the primary tumour. Regression was significantly positively related to PFS ( P = 0.0018, HR = 0.352) and OS ( P = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P = 0.0001, HR = 2.629; OS: P = 0.0003, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"54-62"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2023-03-18DOI: 10.1007/s12291-023-01130-7
Khair Ul Nisa, Najeebul Tarfeen, Shahnaz Ahmad Mir, Ajaz Ahmad Waza, Mir Bilal Ahmad, Bashir Ahmad Ganai
Among the premenopausal women, Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrinopathy affecting the reproductive system and metabolic rhythms leading to disrupted menstrual cycle. Being heterogeneous in nature it is characterized by complex symptomology of oligomennorhoea, excess of androgens triggering masculine phenotypic appearance and/or multiple follicular ovaries. The etiology of this complex disorder remains somewhat doubtful and the researchers hypothesize multisystem links in the pathogenesis of this disease. In this review, we attempt to present several hypotheses that tend to contribute to the etiology of PCOS. Metabolic inflexibility, aberrant pattern of gonadotropin signaling along with the evolutionary, genetic and environmental factors have been discussed. Considered a lifelong endocrinological implication, no universal treatment is available for PCOS so far however; multiple drug therapy is often advised along with simple life style intervention is mainly advised to manage its cardinal symptoms. Here we aimed to present a summarized view of pathophysiological links of PCOS with potential therapeutic strategies.
{"title":"Molecular Mechanisms in the Etiology of Polycystic Ovary Syndrome (PCOS): A Multifaceted Hypothesis Towards the Disease with Potential Therapeutics.","authors":"Khair Ul Nisa, Najeebul Tarfeen, Shahnaz Ahmad Mir, Ajaz Ahmad Waza, Mir Bilal Ahmad, Bashir Ahmad Ganai","doi":"10.1007/s12291-023-01130-7","DOIUrl":"10.1007/s12291-023-01130-7","url":null,"abstract":"<p><p>Among the premenopausal women, Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrinopathy affecting the reproductive system and metabolic rhythms leading to disrupted menstrual cycle. Being heterogeneous in nature it is characterized by complex symptomology of oligomennorhoea, excess of androgens triggering masculine phenotypic appearance and/or multiple follicular ovaries. The etiology of this complex disorder remains somewhat doubtful and the researchers hypothesize multisystem links in the pathogenesis of this disease. In this review, we attempt to present several hypotheses that tend to contribute to the etiology of PCOS. Metabolic inflexibility, aberrant pattern of gonadotropin signaling along with the evolutionary, genetic and environmental factors have been discussed. Considered a lifelong endocrinological implication, no universal treatment is available for PCOS so far however; multiple drug therapy is often advised along with simple life style intervention is mainly advised to manage its cardinal symptoms. Here we aimed to present a summarized view of pathophysiological links of PCOS with potential therapeutic strategies.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"11 1","pages":"18-36"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10784448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83629862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-22DOI: 10.1097/cmr.0000000000000951
Joshua Yee, Cliff Rosendahl, Lauren G Aoude
Clinical dermatoscopy and pathological slide assessment are essential in the diagnosis and management of patients with cutaneous melanoma. For those presenting with stage IIC disease and beyond, radiological investigations are often considered. The dermatoscopic, whole slide and radiological images used during clinical care are often stored digitally, enabling artificial intelligence (AI) and convolutional neural networks (CNN) to learn, analyse and contribute to the clinical decision-making. To review the literature on the progression, capabilities and limitations of AI and CNN and its use in diagnosis and management of cutaneous melanoma. A keyword search of the Medline database for articles relating to cutaneous melanoma. Full-text articles were reviewed if they related to dermatoscopy, pathological slide assessment or radiology. Through analysis of 95 studies, we demonstrate that diagnostic accuracy of AI/CNN can be superior (or at least equal) to clinicians. However, variability in image acquisition, pre-processing, segmentation, and feature extraction remains challenging. With current technological abilities, AI/CNN and clinicians synergistically working together are better than one another in all subspecialty domains relating to cutaneous melanoma. AI has the potential to enhance the diagnostic capabilities of junior dermatology trainees, primary care skin cancer clinicians and general practitioners. For experienced clinicians, AI provides a cost-efficient second opinion. From a pathological and radiological perspective, CNN has the potential to improve workflow efficiency, allowing clinicians to achieve more in a finite amount of time. Until the challenges of AI/CNN are reliably met, however, they can only remain an adjunct to clinical decision-making.
{"title":"The role of artificial intelligence and convolutional neural networks in the management of melanoma: a clinical, pathological, and radiological perspective.","authors":"Joshua Yee, Cliff Rosendahl, Lauren G Aoude","doi":"10.1097/cmr.0000000000000951","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000951","url":null,"abstract":"Clinical dermatoscopy and pathological slide assessment are essential in the diagnosis and management of patients with cutaneous melanoma. For those presenting with stage IIC disease and beyond, radiological investigations are often considered. The dermatoscopic, whole slide and radiological images used during clinical care are often stored digitally, enabling artificial intelligence (AI) and convolutional neural networks (CNN) to learn, analyse and contribute to the clinical decision-making. To review the literature on the progression, capabilities and limitations of AI and CNN and its use in diagnosis and management of cutaneous melanoma. A keyword search of the Medline database for articles relating to cutaneous melanoma. Full-text articles were reviewed if they related to dermatoscopy, pathological slide assessment or radiology. Through analysis of 95 studies, we demonstrate that diagnostic accuracy of AI/CNN can be superior (or at least equal) to clinicians. However, variability in image acquisition, pre-processing, segmentation, and feature extraction remains challenging. With current technological abilities, AI/CNN and clinicians synergistically working together are better than one another in all subspecialty domains relating to cutaneous melanoma. AI has the potential to enhance the diagnostic capabilities of junior dermatology trainees, primary care skin cancer clinicians and general practitioners. For experienced clinicians, AI provides a cost-efficient second opinion. From a pathological and radiological perspective, CNN has the potential to improve workflow efficiency, allowing clinicians to achieve more in a finite amount of time. Until the challenges of AI/CNN are reliably met, however, they can only remain an adjunct to clinical decision-making.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"9 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-22DOI: 10.1097/cmr.0000000000000950
Baptiste Louveau, Coralie Reger De Moura, Fanélie Jouenne, Aurélie Sadoux, Clara Allayous, Laetitia Da Meda, Mélanie Bernard-Cacciarella, Barouyr Baroudjian, Céleste Lebbé, Samia Mourah, Nicolas Dumaz
Upregulation of phosphodiesterase type 4 (PDE4) has been associated with worse prognosis in several cancers. In melanomas harboring NRAS mutations, PDE4 upregulation has been shown to trigger a switch in signaling from BRAF to RAF1 which leads to mitogen-activated protein kinase pathway activation. Previous in vitro evidence showed that PDE4 inhibition induced death in NRASQ61mut melanoma cells and such a strategy may thus be a relevant therapeutic option in those cases with no molecular targeted therapies approved to date. In this study, we generated patient-derived xenografts (PDX) from two NRASQ61mut melanoma lesions. We performed ex vivo histoculture drug response assays and in vivo experiments. A significant ex vivo inhibition of proliferation with the combination of roflumilast+cobimetinib was observed compared to dimethyl sulfoxyde control in both models (51 and 67%). This antiproliferative effect was confirmed in vivo for PDX-1 with a 56% inhibition of tumor growth. To decipher molecular mechanisms underlying this effect, we performed transcriptomic analyses and revealed a decrease in MKI67, RAF1 and CCND1 expression under bitherapy. Our findings strengthen the therapeutic interest of PDE4 inhibitors and support further experiments to evaluate this approach in metastatic melanoma.
{"title":"Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.","authors":"Baptiste Louveau, Coralie Reger De Moura, Fanélie Jouenne, Aurélie Sadoux, Clara Allayous, Laetitia Da Meda, Mélanie Bernard-Cacciarella, Barouyr Baroudjian, Céleste Lebbé, Samia Mourah, Nicolas Dumaz","doi":"10.1097/cmr.0000000000000950","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000950","url":null,"abstract":"Upregulation of phosphodiesterase type 4 (PDE4) has been associated with worse prognosis in several cancers. In melanomas harboring NRAS mutations, PDE4 upregulation has been shown to trigger a switch in signaling from BRAF to RAF1 which leads to mitogen-activated protein kinase pathway activation. Previous in vitro evidence showed that PDE4 inhibition induced death in NRASQ61mut melanoma cells and such a strategy may thus be a relevant therapeutic option in those cases with no molecular targeted therapies approved to date. In this study, we generated patient-derived xenografts (PDX) from two NRASQ61mut melanoma lesions. We performed ex vivo histoculture drug response assays and in vivo experiments. A significant ex vivo inhibition of proliferation with the combination of roflumilast+cobimetinib was observed compared to dimethyl sulfoxyde control in both models (51 and 67%). This antiproliferative effect was confirmed in vivo for PDX-1 with a 56% inhibition of tumor growth. To decipher molecular mechanisms underlying this effect, we performed transcriptomic analyses and revealed a decrease in MKI67, RAF1 and CCND1 expression under bitherapy. Our findings strengthen the therapeutic interest of PDE4 inhibitors and support further experiments to evaluate this approach in metastatic melanoma.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"4 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1097/cmr.0000000000000940
Jie Yan, Haiyan Wang, Xiaoou Lu, Fengjuan Li
The current state of survival prediction models for elderly patients with ulcerative melanoma (uCM) is limited. We sought to develop a nomogram model that can predict overall survival of geriatric patients with uCM. The Surveillance, Epidemiology, and End Results (SEER) database served as a source for patients diagnosed with uCM between 2004 and 2015. Statistical analyses were conducted to determine the significant prognostic elements affecting overall survival using multivariate and univariate Cox proportional risk regression models. Subsequently, an independent forecasting nomogram was developed on the basis of these identified predictors. The predictive model was then assessed and validated through the utilization of receiver operating characteristic curves, calibration curves as well as decision curves. The study included a total of 5019 participants. Univariate and multivariate analyses revealed age, sex, marital status, primary site, tumor size, N stage, M stage, histological type, and surgery were independent prognostic factors. A nomogram was developed using the findings from both univariate and multivariate Cox analyses (P < 0.05). The receiver operating characteristic curves, which vary over time, and the area under the curve (AUC) for the training and validation cohorts, demonstrated the nomogram's strong discriminatory ability. Additionally, the calibration curves indicated satisfactory agreement between the predicted values from the nomogram and the practical outcomes observed in both cohorts. Furthermore, the decision curve analysis curves displayed favorable positive net gains at all times, when the critical value is most likely to occur. In this study, age, sex, marital status, primary site, tumor size, N stage, M stage, histologic type and surgery were determined as independent predictors for elderly patients with uCM. Then, a predictive model with good discriminatory ability was constructed to predict 12-, 24-, and 36-month overall survival in geriatric patients with uCM, which facilitates patients' counseling and individualized medical decision.
{"title":"Development and validation of a nomogram for elderly patients with ulcerative melanoma.","authors":"Jie Yan, Haiyan Wang, Xiaoou Lu, Fengjuan Li","doi":"10.1097/cmr.0000000000000940","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000940","url":null,"abstract":"The current state of survival prediction models for elderly patients with ulcerative melanoma (uCM) is limited. We sought to develop a nomogram model that can predict overall survival of geriatric patients with uCM. The Surveillance, Epidemiology, and End Results (SEER) database served as a source for patients diagnosed with uCM between 2004 and 2015. Statistical analyses were conducted to determine the significant prognostic elements affecting overall survival using multivariate and univariate Cox proportional risk regression models. Subsequently, an independent forecasting nomogram was developed on the basis of these identified predictors. The predictive model was then assessed and validated through the utilization of receiver operating characteristic curves, calibration curves as well as decision curves. The study included a total of 5019 participants. Univariate and multivariate analyses revealed age, sex, marital status, primary site, tumor size, N stage, M stage, histological type, and surgery were independent prognostic factors. A nomogram was developed using the findings from both univariate and multivariate Cox analyses (P < 0.05). The receiver operating characteristic curves, which vary over time, and the area under the curve (AUC) for the training and validation cohorts, demonstrated the nomogram's strong discriminatory ability. Additionally, the calibration curves indicated satisfactory agreement between the predicted values from the nomogram and the practical outcomes observed in both cohorts. Furthermore, the decision curve analysis curves displayed favorable positive net gains at all times, when the critical value is most likely to occur. In this study, age, sex, marital status, primary site, tumor size, N stage, M stage, histologic type and surgery were determined as independent predictors for elderly patients with uCM. Then, a predictive model with good discriminatory ability was constructed to predict 12-, 24-, and 36-month overall survival in geriatric patients with uCM, which facilitates patients' counseling and individualized medical decision.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"20 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1097/cmr.0000000000000948
Erika Richtig, Van A Nguyen, Peter Koelblinger, Ingrid Wolf, Helmut Kehrer, Werner Saxinger, Julia M Ressler, Georg Weinlich, Damian Meyersburg, Christine Hafner, Elisabeth Jecel-Grill, Julian Kofler, Bernhard Lange-Asschenfeldt, Felix Weihsengruber, Klemens Rappersberger, Nina Svastics, Klaus Gasser, Arno Seeber, Franz Kratochvill, Sophie Nagler, Bernhard Mraz, Christoph Hoeller
The efficacy of combined BRAF and MEK inhibition for BRAF V600-mutant melanoma in a broad patient population, including subgroups excluded from phase 3 trials, remains unanswered. This noninterventional study (DATUM-NIS) assessed the real-world efficacy, safety and tolerability of dabrafenib plus trametinib in Austrian patients with unresectable/metastatic melanoma.
{"title":"Dabrafenib plus trametinib in unselected advanced BRAF V600-mut melanoma: a non-interventional, multicenter, prospective trial.","authors":"Erika Richtig, Van A Nguyen, Peter Koelblinger, Ingrid Wolf, Helmut Kehrer, Werner Saxinger, Julia M Ressler, Georg Weinlich, Damian Meyersburg, Christine Hafner, Elisabeth Jecel-Grill, Julian Kofler, Bernhard Lange-Asschenfeldt, Felix Weihsengruber, Klemens Rappersberger, Nina Svastics, Klaus Gasser, Arno Seeber, Franz Kratochvill, Sophie Nagler, Bernhard Mraz, Christoph Hoeller","doi":"10.1097/cmr.0000000000000948","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000948","url":null,"abstract":"The efficacy of combined BRAF and MEK inhibition for BRAF V600-mutant melanoma in a broad patient population, including subgroups excluded from phase 3 trials, remains unanswered. This noninterventional study (DATUM-NIS) assessed the real-world efficacy, safety and tolerability of dabrafenib plus trametinib in Austrian patients with unresectable/metastatic melanoma.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"115 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1097/cmr.0000000000000949
Dimitrios Bafaloukos, Panagiotis Kouzis, Panagiotis Gouveris, Ioannis Boukovinas, Konstantinos Kalbakis, Sofia Baka, Georgios Kyriakakis, Despoina Moschou, Aristea Molfeta, Stamatia Demiri, Dimitrios Mavroudis, Spanoudi Filio, Ioannis Dimitriadis, Helen Gogas
This study primarily aimed to generate real-world evidence (RWE) on the profile and first-line treatment (1LT) patterns of patients with advanced (unresectable Stage III/metastatic) cutaneous melanoma initiated on immuno-oncology (IO)- or targeted therapy (TT)-based 1LT between 1 January 2015 and 1 January 2018 (index period), in routine settings of Greece. This was a multicenter, retrospective chart review study. Eligible consented (unless deceased, for whom consent was waived by the hospital) patients were consecutively included by six oncology clinics. The look-back period extended from informed consent or death to initial melanoma diagnosis. Between 9 Junuary 2021 and 9 February 2022, 225 eligible patients (all Caucasians; 60.4% male; 35.6% diagnosed with de novo advanced melanoma) were included. At 1LT initiation, median age was 62.6 years; 2.7/6.7/90.7% of the patients had Stage IIIB/IIIC/IV disease and 9.3% were unresected. Most frequent metastatic sites were the lung (46.7%), non-regional nodes (33.8%), and liver (20.9%). Among patients, 98.2% had single primary melanoma, 45.6% had disease localized on the trunk, and 63.6% were BRAF-mutant. Of the patients, 45.3% initiated 1LT with an IO-based, 53.3% with a TT-based regimen, and three patients (1.3%) received TT-based followed by IO-based or vice versa. Most common 1LT patterns (frequency ≥10%) were BRAFi/MEKi combination (31.6%), anti-PD-1 monotherapy (25.3%), BRAFi monotherapy (21.8%), and anti-CTLA-4 monotherapy (17.8%). Most frequent regimens were Dabrafenib+Trametinib in 25.3%, and monotherapies with Pembrolizumab/Ipilimumab/Vemurafenib/Dabrafenib in 23.6/17.8/11.1/10.7% of patients, respectively. SUMMER provides RWE on 1LT strategies and profile of patients initiated 1L IO- or TT-based therapy in Greece during the 3-year index period.
{"title":"Real-world management practices and characteristics of patients with advanced melanoma initiated on immuno-oncology or targeted therapy in the first-line setting during the period 2015-2018 in Greece. The 'SUMMER' study: a retrospective multicenter chart review project.","authors":"Dimitrios Bafaloukos, Panagiotis Kouzis, Panagiotis Gouveris, Ioannis Boukovinas, Konstantinos Kalbakis, Sofia Baka, Georgios Kyriakakis, Despoina Moschou, Aristea Molfeta, Stamatia Demiri, Dimitrios Mavroudis, Spanoudi Filio, Ioannis Dimitriadis, Helen Gogas","doi":"10.1097/cmr.0000000000000949","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000949","url":null,"abstract":"This study primarily aimed to generate real-world evidence (RWE) on the profile and first-line treatment (1LT) patterns of patients with advanced (unresectable Stage III/metastatic) cutaneous melanoma initiated on immuno-oncology (IO)- or targeted therapy (TT)-based 1LT between 1 January 2015 and 1 January 2018 (index period), in routine settings of Greece. This was a multicenter, retrospective chart review study. Eligible consented (unless deceased, for whom consent was waived by the hospital) patients were consecutively included by six oncology clinics. The look-back period extended from informed consent or death to initial melanoma diagnosis. Between 9 Junuary 2021 and 9 February 2022, 225 eligible patients (all Caucasians; 60.4% male; 35.6% diagnosed with de novo advanced melanoma) were included. At 1LT initiation, median age was 62.6 years; 2.7/6.7/90.7% of the patients had Stage IIIB/IIIC/IV disease and 9.3% were unresected. Most frequent metastatic sites were the lung (46.7%), non-regional nodes (33.8%), and liver (20.9%). Among patients, 98.2% had single primary melanoma, 45.6% had disease localized on the trunk, and 63.6% were BRAF-mutant. Of the patients, 45.3% initiated 1LT with an IO-based, 53.3% with a TT-based regimen, and three patients (1.3%) received TT-based followed by IO-based or vice versa. Most common 1LT patterns (frequency ≥10%) were BRAFi/MEKi combination (31.6%), anti-PD-1 monotherapy (25.3%), BRAFi monotherapy (21.8%), and anti-CTLA-4 monotherapy (17.8%). Most frequent regimens were Dabrafenib+Trametinib in 25.3%, and monotherapies with Pembrolizumab/Ipilimumab/Vemurafenib/Dabrafenib in 23.6/17.8/11.1/10.7% of patients, respectively. SUMMER provides RWE on 1LT strategies and profile of patients initiated 1L IO- or TT-based therapy in Greece during the 3-year index period.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"20 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-02DOI: 10.1097/CMR.0000000000000926
Marco Rubatto, Silvia Borriello, Nadia Sciamarrelli, Valentina Pala, Luca Tonella, Simone Ribero, Pietro Quaglino
Melanoma is a rare but highly lethal type of skin cancer whose incidence is increasing globally. Melanoma is characterized by high resistance to therapy and relapse. Despite significant advances in the treatment of metastatic melanoma, many patients experience progression due to resistance mechanisms. Epigenetic changes, including alterations in chromatin remodeling, DNA methylation, histone modifications, and non-coding RNA rearrangements, contribute to neoplastic transformation, metastasis, and drug resistance in melanoma. This review summarizes current research on epigenetic mechanisms in melanoma and their therapeutic potential. Specifically, we discuss the role of histone acetylation and methylation in gene expression regulation and melanoma pathobiology, as well as the promising results of HDAC inhibitors and DNMT inhibitors in clinical trials. We also examine the dysregulation of non-coding RNA, particularly miRNAs, and their potential as targets for melanoma therapy. Finally, we highlight the challenges of epigenetic therapies, such as the complexity of epigenetic mechanisms combined with immunotherapies and the need for combination therapies to overcome drug resistance. In conclusion, epigenetic changes may be reversible, and the use of combination therapy between traditional therapies and epigenetically targeted drugs could be a viable solution to reverse the increasing number of patients who develop treatment resistance or even prevent it. While several clinical trials are underway, the complexity of these mechanisms presents a significant challenge to the development of effective therapies. Further research is needed to fully understand the role of epigenetic mechanisms in melanoma and to develop more effective and targeted therapies.
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