EJC Skin Cancer最新文献

英文中文

Morpho-phenotypic characterization of melanoma brain metastases immune microenvironment: A multicentre retrospective study 黑色素瘤脑转移灶免疫微环境的形态表型特征：多中心回顾性研究

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100263

Filippo Nozzoli , Marco Gessi , Filippo Ugolini , Sara Simi , Luca Tinunin , Luigi Francesco Iannone , Alice Esposito , Giovanni Muscas , Alessandro Della Puppa , Isabella Ciardetti , Nicola Pimpinelli , Vincenzo De Giorgi , Isacco Desideri , Lorenzo Livi , Laura Doni , Giovanni Schinzari , Ernesto Rossi , Mario Mandalà , Daniela Massi

Introduction

The recent rise of immunotherapy for melanoma brain metastases (MBM) has enhanced the interest in characterizing the composition of local immune microenvironment. Despite the central nervous system (CNS) is well known for harbouring a peculiar immunological milieu, its role in MBM is only partially understood. The aim of our study was to characterize tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) distribution and density in a cohort of MBM and their potential relevance as prognostic biomarkers.

Materials and methods

Ninety-four MBM patients were retrospectively evaluated for morphological, molecular features and follow-up data. Formalin-fixed and paraffin-embedded (FFPE) tissue sections were immunostained with the following antibodies: CD4, CD8, FoxP3 CD68, CD163, PD-L1, HLA-ABC. Semiquantitative assessment of TILs and TAMs density and spatial distribution was performed and statistical analysis for prognostic correlations was carried out.

Results

The distribution of CD4+ TILs was higher in the intratumoral region (p=0.012) while CD163+ TAMs in the peritumoral (p=0.016). An association was also found between tumour-associated astrogliosis (TAA) and CD163+ TAMs (p=0.021). Increased CD68+ TAMs correlated with BRAF V600 mutation (p=0.038). CD4+ TILs were significantly higher in PD-L1 <1 % group (p=0.030). CD68+ high expression group significantly correlated with PD-L1 ≥1 % (p=0.029). Median HLA-ABC H-score was significantly associated with intratumoral CD4+ (p=0.005) and peritumoral CD8+ infiltration (p=0.048). CD68+ TAMs intratumoral high expression showed a favorable association with OS in patients with multiple MBM (p=0.017), whereas a high HLA-ABC H-score with a prolonged OS in those with single MBM (p=0.007).

Conclusions

Our findings suggest a peculiar topographical distribution of immune cells in both intratumoral and peritumoral areas, and correlations with both BRAF V600 mutation and PD-L1 expression in a large cohort of MBM. Moreover, CD68+ TAMs distribution and HLA-ABC favourably impacted prognosis in patients with multiple and single brain metastases, respectively.

导言：最近，针对黑色素瘤脑转移瘤（MBM）的免疫疗法兴起，这增强了人们对局部免疫微环境组成特征的兴趣。尽管众所周知中枢神经系统（CNS）蕴藏着特殊的免疫环境，但人们对其在脑转移瘤中的作用却知之甚少。我们研究的目的是描述肿瘤浸润淋巴细胞（TILs）和肿瘤相关巨噬细胞（TAMs）在一组髓母细胞瘤中的分布和密度，以及它们作为预后生物标志物的潜在相关性。用以下抗体对福尔马林固定和石蜡包埋（FFPE）组织切片进行免疫染色：CD4、CD8、FoxP3、CD68、CD163、PD-L1、HLA-ABC。结果 CD4+ TILs分布在瘤内区域较高（P=0.012），而 CD163+ TAMs分布在瘤周区域较高（P=0.016）。肿瘤相关星形胶质细胞（TAA）与 CD163+ TAMs 之间也存在关联（p=0.021）。CD68+ TAMs的增加与BRAF V600突变相关（p=0.038）。CD4+ TILs在PD-L1 <1 %组明显增加（p=0.030）。CD68+ 高表达组与 PD-L1 ≥1 % 组明显相关（p=0.029）。HLA-ABC H评分中位数与瘤内CD4+（p=0.005）和瘤周CD8+浸润（p=0.048）明显相关。CD68+瘤内TAMs高表达与多发性MBM患者的OS有良好关系（p=0.017），而高HLA-ABC H-score与单发MBM患者的OS延长有良好关系（p=0.007）。此外，CD68+ TAMs分布和HLA-ABC分别对多发性和单发脑转移患者的预后产生有利影响。

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引用次数: 0

Long-term control with immunotherapy and aggressive re-irradiation for basal cell carcinoma metastatic to the vertebra: A case report and literature review of rare osseous metastasis 通过免疫疗法和积极的再放射治疗长期控制转移至脊椎的基底细胞癌：罕见骨转移的病例报告和文献综述

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100269

Andrew R. Cunningham , Amanda Goetz , Hayley Behm , Andrew W. Ju , Matthew S. Peach

Background

Cutaneous basal cell carcinoma (BCC) is a prevalent malignancy with a rising incidence, though it rarely metastasizes, with an incidence of 0.0028–0.5 %. Hematogenous metastatic BCC (mBCC) is particularly rare and associated with a median survival of 8–14 months.

Case details

This case report details a 59-year-old male with a primary BCC on his left shoulder metastasizing to the lungs and spine. Despite aggressive multimodal treatment, including surgery, radiation, and systemic therapy with hedgehog inhibitors (vismodegib, sonidegib), the disease progressed. At 55 months post-diagnosis, pembrolizumab was introduced due to the high tumor mutation burden (TMB-H), resulting in a notable therapeutic response and prolonged survival. The patient underwent extensive follow-up, including re-irradiation of spinal metastases and immunotherapy, maintaining stable disease for over 101 months.

Results/literature review

A systematic literature review identified only 26 cases of osseous mBCC, primarily treated with surgery and radiation, with variable survival outcomes. This case stands out due to its prolonged survival and novel use of pembrolizumab, highlighting the potential role of immunotherapy in TMB-H mBCC. The patient’s TMB-H status likely contributed to the favorable response to immunotherapy.

Conclusion

This report underscores the importance of genetic profiling in mBCC to identify candidates for emerging immunotherapy treatments. The findings suggest that patients with high mutational burden mBCC may benefit from pembrolizumab, offering a new therapeutic avenue for this rare osseous metastasis.

背景皮肤基底细胞癌（BCC）是一种常见的恶性肿瘤，发病率呈上升趋势，但很少发生转移，发病率为 0.0028-0.5%。血行转移性 BCC（mBCC）尤为罕见，中位生存期为 8-14 个月。本病例报告详细介绍了一名 59 岁男性的病例，他左肩的原发性 BCC 转移至肺部和脊柱。尽管接受了积极的多模式治疗，包括手术、放疗和使用刺猬抑制剂（维斯莫德吉布、索尼德吉布）进行全身治疗，但病情仍在发展。确诊后 55 个月，由于肿瘤突变负荷较高（TMB-H），患者开始使用 pembrolizumab，结果治疗反应显著，生存期延长。该患者接受了广泛的随访，包括脊柱转移灶的再次放射治疗和免疫治疗，在超过 101 个月的时间里病情保持稳定。结果/文献综述系统性文献综述仅发现 26 例骨性 mBCC，主要采用手术和放射治疗，生存结果各不相同。该病例的突出之处在于其延长的生存期和对pembrolizumab的新颖使用，凸显了免疫疗法在TMB-H mBCC中的潜在作用。该患者的 TMB-H 状态很可能是对免疫疗法产生良好反应的原因之一。研究结果表明，高突变负荷的 mBCC 患者可能会从 pembrolizumab 中获益，为这种罕见的骨转移瘤提供了新的治疗途径。

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引用次数: 0

Efficacy and safety of cemiplimab in cutaneous squamous cell carcinoma on chronic wounds: A French retrospective study cemiplimab对慢性伤口皮肤鳞状细胞癌的疗效和安全性：法国的一项回顾性研究

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100273

M. Antoszczak , E. Maubec , A.-B. Duval-Modeste , A. Jannic , C. Jacobzone-Leveque , R. Lesbazeilles , F. Skowron , D. Solub , J. Ancel , L. Mortier , M. Viguier

Background

Chronic wounds increase the risk of the development of cutaneous squamous cell carcinoma (SCC), often resulting in poor prognosis in part because of delayed diagnosis. Cemiplimab, an anti-PD-1 agent, is recommended as first-line treatment for metastatic or locally advanced SCC not eligible for curative surgery, chemotherapy or radiation. However, its efficacy in SCC originating from chronic wounds remains uncertain.

Objective

This retrospective study assessed the efficacy and safety of cemiplimab in patients with SCC originating from chronic wounds.

Methods

We included patients receiving cemiplimab for SCC on chronic wounds between August 2018 and January 2021. The primary endpoint was progression-free survival (PFS) determined by Kaplan-Meier analysis. Secondary endpoints included response rate and safety.

Results

We included 17 patients, predominantly female (59 %), with median age 58 years (interquartile range 49–77). SCC typically originated from leg ulcers (47 %) and presented at locally advanced (41 %) or metastatic stage (41 %). With cemiplimab, often received as third-line therapy (41 %), the median PFS was 6.1 months (95 % confidence interval [CI], 2.97–7.70), with the best response rate 47 % and complete response rate 12 %. We found immune-related adverse events in 24 % of cases. Short PFS was associated with distant metastasis at treatment initiation.

Conclusion

Despite response rates comparable to other SCC types, median PFS was low with cemiplimab treatment for SCC originating from chronic wounds, likely due to the aggressive nature and/or high frequency of altered performance status. Anti-PD-1 therapy remains a primary treatment option for inoperable cases. Further prospective studies are warranted to confirm these findings and optimize treatment strategies.

背景慢性伤口增加了皮肤鳞状细胞癌（SCC）的发病风险，通常导致预后不良，部分原因是诊断延迟。对于不符合根治性手术、化疗或放疗条件的转移性或局部晚期SCC，建议将抗PD-1药物Cemiplimab作为一线治疗药物。本回顾性研究评估了塞米普利单抗在慢性伤口SCC患者中的疗效和安全性。方法我们纳入了2018年8月至2021年1月期间接受塞米普利单抗治疗慢性伤口SCC的患者。主要终点是无进展生存期（PFS），通过卡普兰-梅耶分析确定。次要终点包括反应率和安全性。结果我们纳入了17名患者，主要为女性（59%），中位年龄为58岁（四分位数间距为49-77）。SCC通常源于腿部溃疡（47%），处于局部晚期（41%）或转移期（41%）。塞米普利单抗通常作为三线疗法（41%），中位生存期为 6.1 个月（95% 置信区间 [CI]，2.97-7.70），最佳反应率为 47%，完全反应率为 12%。我们在24%的病例中发现了与免疫相关的不良反应。结论尽管反应率与其他类型的SCC相当，但对慢性伤口引起的SCC进行cemiplimab治疗的中位PFS较低，这可能是由于其侵袭性和/或高频率的表现状态改变所致。抗PD-1疗法仍是无法手术病例的主要治疗方案。有必要进一步开展前瞻性研究，以证实这些发现并优化治疗策略。

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引用次数: 0

Sonidegib reduced tumor burden in patients with advanced basal cell carcinoma in the BOLT trial: Long-term analysis results 在BOLT试验中，Sonidegib减轻了晚期基底细胞癌患者的肿瘤负荷：长期分析结果

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100267

Michael R. Migden , Aaron S. Farberg , James Spencer , Felix Kiecker , Alexander Guminski , Kurt Gebauer , Carmen Loquai , Caroline Robert , Reinhard Dummer , Dirk Schadendorf , Axel Hauschild , Jean Jacques Grob , Nicholas Squittieri , Ramon Arntz , Serena Martelli , Joerg Dierlamm , Ralf Gutzmer

Background

The Hedgehog inhibitor sonidegib had durable efficacy and a manageable safety profile in patients with locally advanced basal cell carcinoma (laBCC) through 42 months of the BOLT trial. In this analysis, we characterize the effects of 200-mg and 800-mg sonidegib on tumors in patients in the BOLT trial.

Methods

Tumors were assessed using color photography and magnetic resonance imaging (MRI) by central and investigator review at baseline; Weeks 5, 9, and 17 after the start of treatment; then every 8 weeks during the first year; and every 12 weeks thereafter.

Results

In patients with laBCC receiving sonidegib, the decrease in best percentage change from baseline in target lesions was 92.3 % per central review and 96.7 % per investigator review in the 200-mg treatment arm, and 90.1 % per central review and 95.2 % per investigator in the 800-mg treatment arm. The kinetics of response to treatment appeared to influence tumor reduction, with patients responding within the first 3 months of treatment experiencing a greater decrease in tumor size over time than later responders. Additionally, patients whose best overall response to treatment was complete response or partial response had a generally longer duration of response compared with patients who had stable disease as best overall response. Tumor reduction and duration of response were greater when assessed by investigator review compared with central review.

Conclusion

Treatment with sonidegib for up to 42 months substantially reduced tumors in patients with laBCC.

背景刺猬蛋白抑制剂索尼替吉对局部晚期基底细胞癌（laBCC）患者具有持久的疗效和可控的安全性，BOLT试验已进行了42个月。方法在基线、治疗开始后的第 5 周、第 9 周和第 17 周、第一年的每 8 周以及之后的每 12 周，通过中心和研究者审查使用彩色照片和磁共振成像 (MRI) 对肿瘤进行评估。结果在接受索尼替吉治疗的laBCC患者中，200毫克治疗组目标病灶与基线相比的最佳变化百分比的下降率为：中央审查92.3%，研究者审查96.7%；800毫克治疗组目标病灶与基线相比的最佳变化百分比的下降率为：中央审查90.1%，研究者审查95.2%。治疗反应的动力学似乎会影响肿瘤的缩小，治疗头 3 个月内有反应的患者的肿瘤大小随着时间的推移会比后来有反应的患者缩小得更多。此外，与以病情稳定为最佳总体反应的患者相比，以完全反应或部分反应为最佳总体反应的患者的反应持续时间一般较长。与中央审查相比，研究人员审查评估的肿瘤缩小程度和反应持续时间更长。

{"title":"Sonidegib reduced tumor burden in patients with advanced basal cell carcinoma in the BOLT trial: Long-term analysis results","authors":"Michael R. Migden , Aaron S. Farberg , James Spencer , Felix Kiecker , Alexander Guminski , Kurt Gebauer , Carmen Loquai , Caroline Robert , Reinhard Dummer , Dirk Schadendorf , Axel Hauschild , Jean Jacques Grob , Nicholas Squittieri , Ramon Arntz , Serena Martelli , Joerg Dierlamm , Ralf Gutzmer","doi":"10.1016/j.ejcskn.2024.100267","DOIUrl":"10.1016/j.ejcskn.2024.100267","url":null,"abstract":"<div><h3>Background</h3><div>The Hedgehog inhibitor sonidegib had durable efficacy and a manageable safety profile in patients with locally advanced basal cell carcinoma (laBCC) through 42 months of the BOLT trial. In this analysis, we characterize the effects of 200-mg and 800-mg sonidegib on tumors in patients in the BOLT trial.</div></div><div><h3>Methods</h3><div>Tumors were assessed using color photography and magnetic resonance imaging (MRI) by central and investigator review at baseline; Weeks 5, 9, and 17 after the start of treatment; then every 8 weeks during the first year; and every 12 weeks thereafter.</div></div><div><h3>Results</h3><div>In patients with laBCC receiving sonidegib, the decrease in best percentage change from baseline in target lesions was 92.3 % per central review and 96.7 % per investigator review in the 200-mg treatment arm, and 90.1 % per central review and 95.2 % per investigator in the 800-mg treatment arm. The kinetics of response to treatment appeared to influence tumor reduction, with patients responding within the first 3 months of treatment experiencing a greater decrease in tumor size over time than later responders. Additionally, patients whose best overall response to treatment was complete response or partial response had a generally longer duration of response compared with patients who had stable disease as best overall response. Tumor reduction and duration of response were greater when assessed by investigator review compared with central review.</div></div><div><h3>Conclusion</h3><div>Treatment with sonidegib for up to 42 months substantially reduced tumors in patients with laBCC.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"2 ","pages":"Article 100267"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528943","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}

引用次数: 0

“One spot check”; a new strategy to increase dermatology access for worrisome skin lesions "单点检查"；增加皮肤科对令人担忧的皮肤病变的诊治机会的新策略

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100116

J. Kips , A. Shen , J. Papeleu , S. Mylle , A. Bosschaert , I. Hoorens , E. Verhaeghe , L. Brochez

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Adverse Effects in Elderly Patients (≥ 85 years old) with Advanced Basal Cell Carcinoma Treated with Sonidegib: A multicenter retrospective study 用 Sonidegib 治疗晚期基底细胞癌老年患者（≥ 85 岁）的不良反应：一项多中心回顾性研究

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100036

L. Martos-Cabrera , M. Bonfill Ortí , G. Deza , R. Fernandez-de-Misa Cabrera , M.N. Hernandez-Hernandez , C. Abril Pérez , R. Botella-Estrada , C. Ciudad Blanco , A. Jaka , M. Just-Sarobé , A. Conde-Taboada , M. Mayor Arenal , E. Vargas-Laguna , E. Masferrer , I. Alcaraz León , L. Leal , S. Medina Montalvo , I. Polo , L. Turrión , B. Hernández , P. Rodríguez-Jiménez

引用次数: 0

Comparison of the efficacy of skin examination using 3D total body photography to clinical and dermoscopic examination 使用三维全身摄影进行皮肤检查与临床和皮肤镜检查的功效比较

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100038

F.F. Gellrich, A. Strunk, J. Steininger, F. Meier, S. Beissert, S. Hobelsberger

引用次数: 0

Cost-of-illness of skin cancer: A systematic review 皮肤癌的疾病成本：系统回顾

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100081

A. Meertens , L. Van Coile , T. Van Iseghem , L. Brochez , N. Verhaeghe , I. Hoorens

引用次数: 0

Immunohistochemical analysis of AMBRA1 and loricrin expression reveals maintained expression in the epidermis overlying a range of benign melanocytic naevi but which may be altered in some melanoma in situ cases 对 AMBRA1 和 loricrin 表达的免疫组化分析表明，在一系列良性黑素细胞痣的表皮层中，AMBRA1 和 loricrin 的表达保持不变，但在某些原位黑色素瘤病例中可能会发生变化。

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100127

A. Husain , P. Lovat , G. Richardson , T. Ness , C. Jones , C. Graham , M. Labus , P. Sloan

引用次数: 0

Efficacy and safety of tirbanibulin 1% ointment for the treatment of actinic keratosis in routine clinical practice in Spain and Italy (TIRBASKIN study) 西班牙和意大利在常规临床实践中使用 1%替班布林软膏治疗光化性角化病的有效性和安全性（TIRBASKIN 研究）

EJC Skin Cancer

Pub Date : 2024-01-01 DOI: 10.1016/j.ejcskn.2024.100030

Y. Gilaberte , O. Yelamos , J. Cañueto , C. Serra-Guillén , A. Conti , F. Pajuelo , A. Lecchi , V. Cappello , B. Kostov , M. Romanelli

引用次数: 0

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