Pub Date : 2024-06-01Epub Date: 2024-02-16DOI: 10.1097/CMR.0000000000000958
Renan J Teixeira, Vinícius G de Souza, Bruna P Sorroche, Victor G Paes, Fabiana A Zambuzi-Roberto, Caio A D Pereira, Vinicius L Vazquez, Lidia M R B Arantes
Elevated neutrophil-to-lymphocyte ratio (NLR) is associated with diminished immunotherapy response in metastatic melanoma. Although NLR assessment in peripheral blood is established, tissue dynamics remain insufficiently explored. This study aimed to evaluate tissue NLR (tNLR)'s predictive potential through immunohistochemistry in immunotherapy-treated melanoma. Fifty melanoma patients who underwent anti-programmed cell death 1 (PD-1) therapy were assessed. Hematological, clinical and tumor features were collected from medical records. Responses were categorized using the Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST) guidelines. Immunohistochemistry for tumor-infiltrating T cells (cluster differentiation 3) and neutrophils (myeloperoxidase) was performed on formalin-fixed paraffin-embedded tumor samples. NLR, derived NLR (dNLR) and tNLR were calculated. Overall survival (OS) and survival following immunotherapy (SFI) were calculated from diagnosis or immunotherapy start to loss of follow-up or death. Patients with high tNLR presented improved OS ( P = 0.038) and SFI with anti-PD-1 therapy ( P = 0.006). Both NLR and dNLR were associated with OS ( P = 0.038 and P = 0.046, respectively) and SFI ( P = 0.001 and P = 0.019, respectively). NLR was also associated with immunotherapy response ( P = 0.007). In conclusion, tNLR emerged as a novel potential biomarker of enhanced survival post anti-PD-1 therapy, in contrast to classical NLR and dNLR markers.
{"title":"Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy.","authors":"Renan J Teixeira, Vinícius G de Souza, Bruna P Sorroche, Victor G Paes, Fabiana A Zambuzi-Roberto, Caio A D Pereira, Vinicius L Vazquez, Lidia M R B Arantes","doi":"10.1097/CMR.0000000000000958","DOIUrl":"10.1097/CMR.0000000000000958","url":null,"abstract":"<p><p>Elevated neutrophil-to-lymphocyte ratio (NLR) is associated with diminished immunotherapy response in metastatic melanoma. Although NLR assessment in peripheral blood is established, tissue dynamics remain insufficiently explored. This study aimed to evaluate tissue NLR (tNLR)'s predictive potential through immunohistochemistry in immunotherapy-treated melanoma. Fifty melanoma patients who underwent anti-programmed cell death 1 (PD-1) therapy were assessed. Hematological, clinical and tumor features were collected from medical records. Responses were categorized using the Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST) guidelines. Immunohistochemistry for tumor-infiltrating T cells (cluster differentiation 3) and neutrophils (myeloperoxidase) was performed on formalin-fixed paraffin-embedded tumor samples. NLR, derived NLR (dNLR) and tNLR were calculated. Overall survival (OS) and survival following immunotherapy (SFI) were calculated from diagnosis or immunotherapy start to loss of follow-up or death. Patients with high tNLR presented improved OS ( P = 0.038) and SFI with anti-PD-1 therapy ( P = 0.006). Both NLR and dNLR were associated with OS ( P = 0.038 and P = 0.046, respectively) and SFI ( P = 0.001 and P = 0.019, respectively). NLR was also associated with immunotherapy response ( P = 0.007). In conclusion, tNLR emerged as a novel potential biomarker of enhanced survival post anti-PD-1 therapy, in contrast to classical NLR and dNLR markers.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746893","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 : 2024-06-01Epub Date: 2024-03-15DOI: 10.1097/CMR.0000000000000965
Marie Leroy, Eve Desmedt, Laure Deramoudt, Michèle Vasseur, Pascal Odou, Hélène Béhal, Bertrand Décaudin, Laurent Mortier, Nicolas Simon
Nivolumab was first authorized at a weight-based dose (WBD) of 3 mg/kg every two weeks (Q2W). Since 2017, a fixed dose (FD) regimen [first 240 mg Q2W and then 480 mg per month (Q4W)] was allowed. The objective of the study was to compare a WBD regimen and an FD regimen with regard to effectiveness and safety. We conducted a single-center, retrospective, real-life study of consecutive adult patients who had received a WBD of nivolumab or an FD of 480 mg Q4W. The primary endpoint was the occurrence of grade ≥3 immune-related adverse events (irAEs). The secondary endpoints were overall survival and cost of the treatment. In all, 342 patients were included: 71 in the WBD cohort and 271 in the FD cohort. Of these patients, 201 patients (59.6%) experienced an irAE, and 24 of these events were graded as ≥3. At 12 months, there was no significant difference in irAE occurrence between the two cohorts [hazard ratio (95% confidence interval): 0.54 (0.21-1.36), P = 0.19]. The 12-month overall survival rate was significantly lower in the WBD cohort ( P < 0.001). Switching from a fortnightly weight dose to a fixed monthly dose halves the cost of hospitalization. Our results did not show a significant difference between WBD and FD cohort in the occurrence of severe irAEs. However overall survival appeared to be significantly higher in FD group. Some clinical trials are investigating a hybrid dosing regimen in which a WBD is capped by an FD. The present results need to be confirmed in prospective studies.
{"title":"Retrospective comparison of a weight-based dose every 2 weeks with a fixed dose every month: a real-life analysis of nivolumab in the treatment of advanced melanoma.","authors":"Marie Leroy, Eve Desmedt, Laure Deramoudt, Michèle Vasseur, Pascal Odou, Hélène Béhal, Bertrand Décaudin, Laurent Mortier, Nicolas Simon","doi":"10.1097/CMR.0000000000000965","DOIUrl":"10.1097/CMR.0000000000000965","url":null,"abstract":"<p><p>Nivolumab was first authorized at a weight-based dose (WBD) of 3 mg/kg every two weeks (Q2W). Since 2017, a fixed dose (FD) regimen [first 240 mg Q2W and then 480 mg per month (Q4W)] was allowed. The objective of the study was to compare a WBD regimen and an FD regimen with regard to effectiveness and safety. We conducted a single-center, retrospective, real-life study of consecutive adult patients who had received a WBD of nivolumab or an FD of 480 mg Q4W. The primary endpoint was the occurrence of grade ≥3 immune-related adverse events (irAEs). The secondary endpoints were overall survival and cost of the treatment. In all, 342 patients were included: 71 in the WBD cohort and 271 in the FD cohort. Of these patients, 201 patients (59.6%) experienced an irAE, and 24 of these events were graded as ≥3. At 12 months, there was no significant difference in irAE occurrence between the two cohorts [hazard ratio (95% confidence interval): 0.54 (0.21-1.36), P = 0.19]. The 12-month overall survival rate was significantly lower in the WBD cohort ( P < 0.001). Switching from a fortnightly weight dose to a fixed monthly dose halves the cost of hospitalization. Our results did not show a significant difference between WBD and FD cohort in the occurrence of severe irAEs. However overall survival appeared to be significantly higher in FD group. Some clinical trials are investigating a hybrid dosing regimen in which a WBD is capped by an FD. The present results need to be confirmed in prospective studies.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137010","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 : 2024-06-01Epub Date: 2024-03-28DOI: 10.1097/CMR.0000000000000963
Marie Fabre, Anouck Lamoureux, Laurent Meunier, Quentin Samaran, Candice Lesage, Céline Girard, Aurélie Du Thanh, Lionel Moulis, Olivier Dereure
Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency of CNS targets and tolerance of second-line combined anti-PD1/dual-targeted anti-BRAF/anti-MEK therapy implemented in patients with CNS progression after initially efficient first-line combined targeted therapy in patients with BRAF-mutated melanoma in a real-life setting. A monocentric retrospective analysis including all such patients treated from January 2017 to January 2022 was conducted in our tertiary referral center. The response of CNS lesions to second-line triple therapy was assessed through monthly clinical and at least quarterly morphological (according to RECIST criteria) evaluation. Tolerance data were also collected. Seventeen patients were included with a mean follow-up of 2.59 (±2.43) months. Only 1 patient displayed a significant clinical and morphological response. No statistically significant difference was observed between patients receiving or not additional local therapy (mainly radiotherapy) as to response achievement. Immunotherapy was permanently discontinued in 1 patient owing to grade 4 toxicity. Mean PFS and OS after CNS progression were 2.59 and 4.12 months, respectively. In this real-life survey, the subsequent addition of anti-PD1 to combined targeted therapy in melanoma patients with upfront CNS metastases did not result in significant response of CNS targets in most BRAF mutated melanoma patients with secondary CNS progression after initially successful first-line combined targeted therapy.
{"title":"Efficiency and tolerance of second-line triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in BRAF mutated melanoma patients with central nervous system metastases occurring during first-line combined targeted therapy: a real-life survey.","authors":"Marie Fabre, Anouck Lamoureux, Laurent Meunier, Quentin Samaran, Candice Lesage, Céline Girard, Aurélie Du Thanh, Lionel Moulis, Olivier Dereure","doi":"10.1097/CMR.0000000000000963","DOIUrl":"10.1097/CMR.0000000000000963","url":null,"abstract":"<p><p>Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency of CNS targets and tolerance of second-line combined anti-PD1/dual-targeted anti-BRAF/anti-MEK therapy implemented in patients with CNS progression after initially efficient first-line combined targeted therapy in patients with BRAF-mutated melanoma in a real-life setting. A monocentric retrospective analysis including all such patients treated from January 2017 to January 2022 was conducted in our tertiary referral center. The response of CNS lesions to second-line triple therapy was assessed through monthly clinical and at least quarterly morphological (according to RECIST criteria) evaluation. Tolerance data were also collected. Seventeen patients were included with a mean follow-up of 2.59 (±2.43) months. Only 1 patient displayed a significant clinical and morphological response. No statistically significant difference was observed between patients receiving or not additional local therapy (mainly radiotherapy) as to response achievement. Immunotherapy was permanently discontinued in 1 patient owing to grade 4 toxicity. Mean PFS and OS after CNS progression were 2.59 and 4.12 months, respectively. In this real-life survey, the subsequent addition of anti-PD1 to combined targeted therapy in melanoma patients with upfront CNS metastases did not result in significant response of CNS targets in most BRAF mutated melanoma patients with secondary CNS progression after initially successful first-line combined targeted therapy.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306183","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}
Melanoma is known for its high metastatic potential and aggressive growth. Recurrence is common post-surgery, sometimes leading to unresectable disease. Locally recurrent unresectable melanoma of extremity has been treated with high-dose anticancer chemotherapy via isolated limb perfusion (ILP) to improve local efficacy of drug and salvage limbs. Standard ILP monitoring uses radiolabeled dyes, requiring specialized personnel and involving radiation exposure. In this case, we used indocyanine green (ICG) to track systemic drug leakage during ILP. A 47-year-old gentleman with recurrent malignant melanoma of the left foot, operated twice earlier and treated with adjuvant pembrolizumab, presented with multiple in-transit metastases in the limb. ILP was planned, with 5 mg ICG administered in the perfusion solution along with high-dose melphalan. Stryker's SPI PHI handheld device was employed to visualize ICG during ILP. Absence of fluorescence beyond the involved extremity, such as fingers, ears, and the abdominal wall, indicated no systemic drug dispersion. For control, technetium radiocolloid dye was co-administered, monitored by a precordial gamma probe, confirming no systemic leakage, and validating effectiveness of ICG in leakage monitoring. ICG proves to be a safe, reliable, cost-effective, radiation-free approach for precise systemic drug leakage monitoring during ILP for recurrent melanoma of extremity.
{"title":"Feasibility and efficacy of indocyanine green in monitoring systemic drug leakage during isolated limb perfusion for recurrent melanoma of extremity.","authors":"Sri Siddharth Nekkanti, Syed Nusrath, Rajesh Jarang, Basanth Kumar Rayani, Yerramshetty Vamshi Krishna, Kalidindi Venkata Vijaya Narsimha Raju","doi":"10.1097/CMR.0000000000000967","DOIUrl":"10.1097/CMR.0000000000000967","url":null,"abstract":"<p><p>Melanoma is known for its high metastatic potential and aggressive growth. Recurrence is common post-surgery, sometimes leading to unresectable disease. Locally recurrent unresectable melanoma of extremity has been treated with high-dose anticancer chemotherapy via isolated limb perfusion (ILP) to improve local efficacy of drug and salvage limbs. Standard ILP monitoring uses radiolabeled dyes, requiring specialized personnel and involving radiation exposure. In this case, we used indocyanine green (ICG) to track systemic drug leakage during ILP. A 47-year-old gentleman with recurrent malignant melanoma of the left foot, operated twice earlier and treated with adjuvant pembrolizumab, presented with multiple in-transit metastases in the limb. ILP was planned, with 5 mg ICG administered in the perfusion solution along with high-dose melphalan. Stryker's SPI PHI handheld device was employed to visualize ICG during ILP. Absence of fluorescence beyond the involved extremity, such as fingers, ears, and the abdominal wall, indicated no systemic drug dispersion. For control, technetium radiocolloid dye was co-administered, monitored by a precordial gamma probe, confirming no systemic leakage, and validating effectiveness of ICG in leakage monitoring. ICG proves to be a safe, reliable, cost-effective, radiation-free approach for precise systemic drug leakage monitoring during ILP for recurrent melanoma of extremity.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137009","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 : 2024-06-01Epub Date: 2024-02-16DOI: 10.1097/CMR.0000000000000957
Wei Zhang, Shuai Wang
Intratumor heterogeneity (ITH) is defined as differences in molecular and phenotypic profiles between different tumor cells and immune cells within a tumor. ITH was involved in the cancer progression, aggressiveness, therapy resistance and cancer recurrence. Integrative machine learning procedure including 10 methods was conducted to develop an ITH-related signature (IRS) in The Cancer Genome Atlas (TCGA), GSE54467, GSE59455 and GSE65904 cohort. Several scores, including tumor immune dysfunction and exclusion (TIDE) score, tumor mutation burden (TMB) score and immunophenoscore (IPS), were used to evaluate the role of IRS in predicting immunotherapy benefits. Two immunotherapy datasets (GSE91061 and GSE78220) were utilized to the role of IRS in predicting immunotherapy benefits of skin cutaneous melanoma (SKCM) patients. The optimal prognostic IRS constructed by Lasso method acted as an independent risk factor and had a stable and powerful performance in predicting the overall survival rate in SKCM, with the area under the curve of 2-, 3- and 4-year receiver operating characteristic curve being 0.722, 0.722 and 0.737 in TCGA cohort. We also constructed a nomogram and the actual 1-, 3- and 5-year survival times were highly consistent with the predicted survival times. SKCM patients with low IRS scores had a lower TIDE score, lower immune escape score and higher TMB score, higher PD1&CTLA4 IPS. Moreover, SKCM patients with low IRS scores had a lower gene sets score involved in DNA repair, angiogenesis, glycolysis, hypoxia, IL2-STAT5 signaling, MTORC1 signaling, NOTCH signaling and P53 pathway. The current study constructed a novel IRS in SKCM using 10 machine learning methods. This IRS acted as an indicator for predicting the prognosis and immunotherapy benefits of SKCM patients.
{"title":"Machine learning developed an intratumor heterogeneity signature for predicting prognosis and immunotherapy benefits in skin cutaneous melanoma.","authors":"Wei Zhang, Shuai Wang","doi":"10.1097/CMR.0000000000000957","DOIUrl":"10.1097/CMR.0000000000000957","url":null,"abstract":"<p><p>Intratumor heterogeneity (ITH) is defined as differences in molecular and phenotypic profiles between different tumor cells and immune cells within a tumor. ITH was involved in the cancer progression, aggressiveness, therapy resistance and cancer recurrence. Integrative machine learning procedure including 10 methods was conducted to develop an ITH-related signature (IRS) in The Cancer Genome Atlas (TCGA), GSE54467, GSE59455 and GSE65904 cohort. Several scores, including tumor immune dysfunction and exclusion (TIDE) score, tumor mutation burden (TMB) score and immunophenoscore (IPS), were used to evaluate the role of IRS in predicting immunotherapy benefits. Two immunotherapy datasets (GSE91061 and GSE78220) were utilized to the role of IRS in predicting immunotherapy benefits of skin cutaneous melanoma (SKCM) patients. The optimal prognostic IRS constructed by Lasso method acted as an independent risk factor and had a stable and powerful performance in predicting the overall survival rate in SKCM, with the area under the curve of 2-, 3- and 4-year receiver operating characteristic curve being 0.722, 0.722 and 0.737 in TCGA cohort. We also constructed a nomogram and the actual 1-, 3- and 5-year survival times were highly consistent with the predicted survival times. SKCM patients with low IRS scores had a lower TIDE score, lower immune escape score and higher TMB score, higher PD1&CTLA4 IPS. Moreover, SKCM patients with low IRS scores had a lower gene sets score involved in DNA repair, angiogenesis, glycolysis, hypoxia, IL2-STAT5 signaling, MTORC1 signaling, NOTCH signaling and P53 pathway. The current study constructed a novel IRS in SKCM using 10 machine learning methods. This IRS acted as an indicator for predicting the prognosis and immunotherapy benefits of SKCM patients.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746894","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 : 2024-06-01Epub Date: 2024-03-11DOI: 10.1097/CMR.0000000000000960
Peizhou Wang, Tun Liu, Qingguo Zhang, Pan Luo
Currently, numerous studies suggest a potential association between the gut microbiota and the progression of melanoma. Hence, our objective was to examine the genetic impact of the gut microbiota on melanoma through the utilization of the Mendelian randomization (MR) approach. This research employed Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae as exposure variables and cutaneous melanoma (CM) as the outcome in a two-sample MR analysis. In this MR research, the primary analytical approach was the random-effects inverse-variance weighting (IVW) model. Complementary methods included weighted median, MR Egger, and basic and weighted models. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual SNP. The random-effects IVW outcomes indicated that Streptococcus, Bacteroides, Lachnospiraceae and Proteobacteria had no causal relationship with CM, with odds ratios of 1.001 [95% confidence interval (CI) = 0.998-1.004, P = 0.444], 0.999 (95% CI = 0.996-1.002, P = 0.692), 1.001 (95% CI = 0.998-1.003, P = 0.306), and 0.999 (95% CI = 0.997-1.002, P = 0.998), respectively. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. Our research determined that Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae do not induce CM at the genetic level. However, we cannot dismiss the possibility that these four gut microbiotas might influence CM through other mechanisms.
目前,许多研究表明,肠道微生物群与黑色素瘤的进展之间存在潜在联系。因此,我们的目标是通过孟德尔随机化(MR)方法,研究肠道微生物群对黑色素瘤的遗传影响。本研究采用乳酸菌、链球菌、变形菌和漆螺菌作为暴露变量,以皮肤黑色素瘤(CM)作为结果,进行双样本 MR 分析。在这项磁共振研究中,主要分析方法是随机效应逆方差加权(IVW)模型。补充方法包括加权中位数、MR Egger、基本模型和加权模型。我们在研究中评估了异质性和水平多向性,仔细检查分析结果是否受到任何单个 SNP 的影响。随机效应 IVW 结果表明,链球菌属、乳杆菌属、拉克氏螺旋体属和变形菌属与 CM 没有因果关系,其几率比为 1.001 [95% 置信区间 (CI) = 0.998-1.004,P = 0.444]、0.999(95% CI = 0.996-1.002,P = 0.692)、1.001(95% CI = 0.998-1.003,P = 0.306)和 0.999(95% CI = 0.997-1.002,P = 0.998)。没有分析显示异质性、水平多效性或偏差。我们的研究确定,乳酸杆菌、链球菌、变形菌和漆树菌在基因水平上不会诱导中耳炎。但是,我们不能排除这四种肠道微生物通过其他机制影响中风的可能性。
{"title":"Genetic causal relationship between gut microbiota and cutaneous melanoma: a two-sample Mendelian randomization study.","authors":"Peizhou Wang, Tun Liu, Qingguo Zhang, Pan Luo","doi":"10.1097/CMR.0000000000000960","DOIUrl":"10.1097/CMR.0000000000000960","url":null,"abstract":"<p><p>Currently, numerous studies suggest a potential association between the gut microbiota and the progression of melanoma. Hence, our objective was to examine the genetic impact of the gut microbiota on melanoma through the utilization of the Mendelian randomization (MR) approach. This research employed Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae as exposure variables and cutaneous melanoma (CM) as the outcome in a two-sample MR analysis. In this MR research, the primary analytical approach was the random-effects inverse-variance weighting (IVW) model. Complementary methods included weighted median, MR Egger, and basic and weighted models. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual SNP. The random-effects IVW outcomes indicated that Streptococcus, Bacteroides, Lachnospiraceae and Proteobacteria had no causal relationship with CM, with odds ratios of 1.001 [95% confidence interval (CI) = 0.998-1.004, P = 0.444], 0.999 (95% CI = 0.996-1.002, P = 0.692), 1.001 (95% CI = 0.998-1.003, P = 0.306), and 0.999 (95% CI = 0.997-1.002, P = 0.998), respectively. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. Our research determined that Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae do not induce CM at the genetic level. However, we cannot dismiss the possibility that these four gut microbiotas might influence CM through other mechanisms.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101999","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 : 2024-04-29DOI: 10.1097/cmr.0000000000000969
Ahmet Anil Ozluk, Damla Gunenc, Saadet Sim Yildirim, Burcak Karaca
With the widespread use of immune checkpoint inhibitors, management of immune-related adverse effects specific to these treatments became an important research era in patient management. Among these, immune-related hepatotoxicity (IRH) is an adverse event that can be fatal. While the first-line treatment of IRH is well established, there is still no consensus regarding the management approach for steroid-refractory, severe IRH. Here, we report four patients with metastatic melanoma who developed IRH during antiprogrammed cell death protein-1 plus anticytotoxic T-lymphocyte-associated protein-4 combination therapy and review of the literature. All of our patients were steroid-refractory and were successfully treated with tocilizumab. Given the rapid improvement in liver enzymes and patient's clinical status with tocilizumab, this treatment should be prioritized in steroid-refractory IRH.
{"title":"Tocilizumab in the treatment of steroid refractory immune-related hepatotoxicity: a case series and review of the literature.","authors":"Ahmet Anil Ozluk, Damla Gunenc, Saadet Sim Yildirim, Burcak Karaca","doi":"10.1097/cmr.0000000000000969","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000969","url":null,"abstract":"With the widespread use of immune checkpoint inhibitors, management of immune-related adverse effects specific to these treatments became an important research era in patient management. Among these, immune-related hepatotoxicity (IRH) is an adverse event that can be fatal. While the first-line treatment of IRH is well established, there is still no consensus regarding the management approach for steroid-refractory, severe IRH. Here, we report four patients with metastatic melanoma who developed IRH during antiprogrammed cell death protein-1 plus anticytotoxic T-lymphocyte-associated protein-4 combination therapy and review of the literature. All of our patients were steroid-refractory and were successfully treated with tocilizumab. Given the rapid improvement in liver enzymes and patient's clinical status with tocilizumab, this treatment should be prioritized in steroid-refractory IRH.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826709","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 : 2024-04-24DOI: 10.1097/CMR.0000000000000966
Hemali Shah, Rose Parisi, Emily Everdell, Paul Feustel, Lindy Davis
{"title":"The effect of COVID-19 on early melanoma detection.","authors":"Hemali Shah, Rose Parisi, Emily Everdell, Paul Feustel, Lindy Davis","doi":"10.1097/CMR.0000000000000966","DOIUrl":"https://doi.org/10.1097/CMR.0000000000000966","url":null,"abstract":"","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140665874","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 : 2024-04-22DOI: 10.1097/cmr.0000000000000972
Yao Gao, Yao Wang, Yueyue Luo, Yong Zhang, Saiqi Wang, Xiance Tang, Peng Qin, Benling Xu, Quanli Gao, Tiepeng Li
The aim of this study is to determine whether the pretreatment CD8+PD-1+ to CD4+PD-1+ (PERLS) ratio is an independent risk prognostic factor of advanced melanoma patients. We retrospectively analyzed the efficacy and flow cytometry data from advanced melanoma patients who received PD-1 inhibitor as monotherapy between January 1, 2018 and January 26, 2022. Fifty-nine patients were enrolled, the PERLS cutoff was 1.125. PERLS did not correlate with clinical characteristics but were significantly associated with baseline CD8+, CD4+, and CD8+PD-1+ T cells. The mean overall survival and the progression-free survival were 45.8 and 17.1 months for the low PERLS group (n = 39), compared with 29.9 (P = 0.001) and 9.7 (P = 0.003) months for the high PERLS group (n = 20), respectively. Pretreatment PERLS might contribute to selecting patients before receiving anti-PD-1 therapy.
{"title":"Pretreatment CD8+PD-1+ to CD4+PD-1+ ratio is associated with the prognosis of advanced melanoma patients treated with PD-1 inhibitors.","authors":"Yao Gao, Yao Wang, Yueyue Luo, Yong Zhang, Saiqi Wang, Xiance Tang, Peng Qin, Benling Xu, Quanli Gao, Tiepeng Li","doi":"10.1097/cmr.0000000000000972","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000972","url":null,"abstract":"The aim of this study is to determine whether the pretreatment CD8+PD-1+ to CD4+PD-1+ (PERLS) ratio is an independent risk prognostic factor of advanced melanoma patients. We retrospectively analyzed the efficacy and flow cytometry data from advanced melanoma patients who received PD-1 inhibitor as monotherapy between January 1, 2018 and January 26, 2022. Fifty-nine patients were enrolled, the PERLS cutoff was 1.125. PERLS did not correlate with clinical characteristics but were significantly associated with baseline CD8+, CD4+, and CD8+PD-1+ T cells. The mean overall survival and the progression-free survival were 45.8 and 17.1 months for the low PERLS group (n = 39), compared with 29.9 (P = 0.001) and 9.7 (P = 0.003) months for the high PERLS group (n = 20), respectively. Pretreatment PERLS might contribute to selecting patients before receiving anti-PD-1 therapy.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677077","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 : 2024-04-18DOI: 10.1097/cmr.0000000000000974
Lawrence W Wu, Jacqueline J Tao, Diana McDonnell, Benjamin Izar
Pseudoprogression encapsulates a process of temporary radiographic growth followed by subsequent regression of metastatic melanoma lesions in response to immune checkpoint blockade (ICB), such as the combination of anti-programmed cell death protein 1 (PD-1) and anticytotoxic T-lymphocyte-associated antigen 4 therapy. This occurs in approximately 5-10% of ICB-treated patients, but has not yet been described in the context of novel combination therapies. Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy. The patient experienced a radiographic increase in liver metastatic lesion size, but was found to have a subsequent reduction in these lesions. The patient has been on therapy for 18 months without evidence of disease progression and continues to be clinically well-appearing.
{"title":"Pseudoprogression in a patient with metastatic melanoma treated with PD-1 and LAG-3 inhibition.","authors":"Lawrence W Wu, Jacqueline J Tao, Diana McDonnell, Benjamin Izar","doi":"10.1097/cmr.0000000000000974","DOIUrl":"https://doi.org/10.1097/cmr.0000000000000974","url":null,"abstract":"Pseudoprogression encapsulates a process of temporary radiographic growth followed by subsequent regression of metastatic melanoma lesions in response to immune checkpoint blockade (ICB), such as the combination of anti-programmed cell death protein 1 (PD-1) and anticytotoxic T-lymphocyte-associated antigen 4 therapy. This occurs in approximately 5-10% of ICB-treated patients, but has not yet been described in the context of novel combination therapies. Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy. The patient experienced a radiographic increase in liver metastatic lesion size, but was found to have a subsequent reduction in these lesions. The patient has been on therapy for 18 months without evidence of disease progression and continues to be clinically well-appearing.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631148","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}