Melanoma Management最新文献

英文中文

An evidence-based approach to positive sentinel node disease: should we ever do a completion node dissection? 前哨淋巴结阳性疾病的循证治疗方法:我们是否应该进行完全性淋巴结清扫?

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-10-18 DOI: 10.2217/mmt-2019-0011

J. Downs, D. Gyorki

Management of later stage melanoma has undergone significant changes. Sentinel node biopsy has long been an accepted method of staging, but two recent randomized-controlled trials have provided an evidence base for decision making about completion lymphadenectomy. They showed no survival advantage in further surgery for patients with positive sentinel node biopsies. There is now no evidence to support completion lymphadenectomy in the majority of patients, and this is reflected in international practice guidelines.

晚期黑色素瘤的治疗已经发生了重大变化。前哨淋巴结活检长期以来一直是一种公认的分期方法，但最近的两项随机对照试验为完全淋巴结切除术的决策提供了证据基础。前哨淋巴结活检阳性的患者在进一步手术中没有生存优势。目前没有证据支持大多数患者行完全淋巴结切除术，这也反映在国际实践指南中。

引用次数: 4

The emergence of neoadjuvant therapy in advanced melanoma 晚期黑色素瘤新辅助治疗的出现

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-10-18 DOI: 10.2217/mmt-2019-0007

James X. Sun, Dennis Kirichenko, J. Zager, Z. Eroglu

The discovery of immunotherapy and targeted therapy has introduced new and effective treatment options for advanced melanoma, providing therapeutic options where none existed before. The natural extension of these novel therapies is to identify their role in the neoadjuvant setting. Neoadjuvant therapy for advanced melanoma is still in its infancy, with a wealth of clinical trials underway. Early results are promising, allowing for management of a disease that previously had few options. We review the current literature and interim results from several ongoing investigations to understand the current state of neoadjuvant treatment options and what is to come. These studies pave the way for further advancements in melanoma therapy.

免疫疗法和靶向治疗的发现为晚期黑色素瘤提供了新的有效治疗方案，提供了以前没有的治疗方案。这些新疗法的自然延伸是确定它们在新佐剂环境中的作用。晚期黑色素瘤的新辅助治疗仍处于起步阶段，大量临床试验正在进行中。早期的结果是有希望的，允许管理以前几乎没有选择的疾病。我们回顾了目前的文献和几项正在进行的研究的中期结果，以了解新辅助治疗方案的现状和未来的发展。这些研究为黑色素瘤治疗的进一步发展铺平了道路。

引用次数: 13

Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review. 辅助治疗与术后观察等待治疗III期黑色素瘤：多国回顾性图表综述。

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-10-04 DOI: 10.2217/mmt-2019-0015

Peter Mohr, Felix Kiecker, Virtudes Soriano, Olivier Dereure, Karmele Mujika, Philippe Saiag, Jochen Utikal, Rama Koneru, Caroline Robert, Florencia Cuadros, Matias Chacón, Rodrigo U Villarroel, Yana G Najjar, Lisa Kottschade, Eva M Couselo, Roy Koruth, Annie Guérin, Rebecca Burne, Raluca Ionescu-Ittu, Maurice Perrinjaquet, Jonathan S Zager

Aim: To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011-2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait.

Methods: Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe.

Results: Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy.

Conclusion: Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.

目的：描述2011-2016年接受手术切除的III期黑色素瘤患者的治疗模式，并评估随后接受系统辅助治疗的患者与观望者的疗效。方法：对来自北美17个黑色素瘤中心的380名患者进行图表回顾，结果：129名（34%）接受辅助治疗的患者中，85%接受干扰素α-2b治疗，56%停止治疗（主要是由于不良事件）。与观察和等待相比，接受辅助治疗的患者无复发生存期明显更长（危险比=0.63；p<0.05）。辅助治疗方案和剂量存在相当大的异质性。在接受干扰素辅助治疗的患者中也发现了类似的结果。结论：具有更好安全性/有效性的辅助疗法将改善III期黑色素瘤患者的临床结果。

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引用次数: 4

Topical and intralesional therapies for in-transitmelanoma 转移期黑色素瘤的局部和病灶内治疗

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-09-02 DOI: 10.2217/mmt-2019-0008

M. Henderson

This report surveys the role of topical and intralesional agents in the management of in-transit melanoma. The extent and progression of in-transit disease is highly variable and many patients can have a protracted period of locoregional control. These agents are useful in the management of patients who have progressed beyond local surgical excision in whom more aggressive therapies, such as isolated limb infusion or use of talimogene laherparepvec, are not appropriate or have failed. In general, these agents are modestly effective and associated with frequent but only minor toxicity. As the mechanism of action of many of these agents includes initiation of a local immune response, combinations with immune checkpoint inhibitors are currently being explored.

本报告调查了局部和局部药物在运输中的黑色素瘤管理中的作用。过境疾病的范围和进展是高度可变的，许多患者可以有一个长期的局部区域控制。这些药物对于局部手术切除后进展的患者是有用的，在这些患者中，更积极的治疗，如孤立肢体输注或使用talimogene laherparepvec，是不合适的或失败的。一般来说，这些药物的效果一般，并伴有频繁但仅轻微的毒性。由于许多这些药物的作用机制包括启动局部免疫反应，目前正在探索与免疫检查点抑制剂的联合。

引用次数: 2

Systemic therapies for unresectable locoregional melanoma: a significant area of need 不可切除的局部黑色素瘤的全身治疗:一个重要的需要领域

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-09-02 DOI: 10.2217/mmt-2019-0010

E. Nan Tie, J. Lai-Kwon, D. Gyorki

Immune checkpoint inhibitors and BRAF-MEK inhibitors have revolutionized the management and prognosis of patients with metastatic melanoma. However, there is minimal evidence to guide their incorporation into current treatment paradigms for unresectable stage III disease. The era of effective systemic therapies has prompted a discussion about what constitutes unresectable disease. Patients with unresectable stage III disease can experience significant morbidity from their disease and locoregional therapies, and may progress with distant metastases. Despite increasing use of systemic therapies in unresectable stage III disease, further evidence is needed to establish their degree of benefit in this population.

免疫检查点抑制剂和BRAF-MEK抑制剂已经彻底改变了转移性黑色素瘤患者的管理和预后。然而，很少有证据指导将其纳入目前不可切除的III期疾病的治疗范例。有效的全身治疗的时代已经引发了关于什么是不可切除疾病的讨论。不可切除的III期疾病患者可经历其疾病和局部治疗的显著发病率，并可能进展为远处转移。尽管在不可切除的III期疾病中越来越多地使用全身疗法，但需要进一步的证据来确定它们在这一人群中的获益程度。

引用次数: 7

Journal Watch: our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of melanoma management. 期刊观察:我们的专家小组重点介绍了与黑色素瘤管理领域相关的各种主题中最重要的研究文章。

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-06-14 DOI: 10.2217/mmt-2019-0002

Robert V Rawson, Teresa Bailey, Andrew J Colebatch, Peter Ferguson

Hauschild A, Dummer R, Schadendorf D et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant Stage III melanoma. J. Clin. Oncol. 36(35), 3441–3449 (2018) This publication, an update of the COMBI-AD trial, provides the most mature data with extended follow-up in Stage III metastatic melanoma patients treated with immune checkpoint or targeted therapies in the adjuvant setting. The results of this study of Stage III BRAF V600 mutant metastatic melanoma continue to show relapse-free survival (RFS) benefit at 40 months of dabrafenib plus trametinib therapy over placebo with an absolute difference of almost 20% between the arms. The RFS benefit was also confirmed regardless of stage, clinical and pathological subgroups. For the first time, the somewhat controversial, Weibull mixture cure-rate analysis has been used in metastatic melanoma patients and showed estimated cure rates of 54% (treatment arm) versus 37% (placebo arm). Moving forward it will be interesting to compare these results with the results of immunotherapy and combinations therapy trials in the adjuvant and neoadjuvant setting to ascertain the optimal treatment protocol for BRAF-mutant metastatic melanoma patients. – Written by Robert V Rawson

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引用次数: 0

Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1) talimogene laherparepvec在美国临床应用于黑色素瘤的观察研究（COSMUS-1）

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-06-01 DOI: 10.2217/mmt-2019-0012

M. Perez, J. Zager, T. Amatruda, R. Conry, C. Ariyan, Anupam M. Desai, J. Kirkwood, S. Treichel, D. Cohan, L. Raskin

Aim: Talimogene laherparepvec (T-VEC) is an intralesional treatment for unresectable cutaneous, subcutaneous and nodal melanoma. COSMUS-1 was conducted to examine how T-VEC is used in US clinical practice. Materials & methods: A chart review was conducted at seven centers, with 78 patients screened and 76 eligible. Results: Patients began treatment with T-VEC between October 2015 and December 2016. Median follow-up was 9.4 months. Twenty percent of patients (n = 15) completed T-VEC treatment with no remaining injectable lesions or pathologic complete response. Flu-like symptoms were the most commonly reported adverse events (n = 8; 10.5%), followed by lesion ulceration (n = 4; 5.3%). No herpetic lesions or infections were reported. Conclusion: T-VEC was well tolerated and showed clinical utility.

目的：Talimogene laherparepvec（T-VEC）是一种不可切除的皮肤、皮下和淋巴结黑色素瘤的病灶内治疗方法。COSMUS-1旨在研究T-VEC在美国临床实践中的应用。材料和方法：在七个中心进行了图表审查，共有78名患者接受了筛查，76名符合条件。结果：患者于2015年10月至2016年12月开始接受T-VEC治疗。中位随访时间为9.4个月。20%的患者（n=15）完成了T-VEC治疗，没有剩余的可注射病变或病理学完全反应。流感样症状是最常见的不良事件（n=8；10.5%），其次是病变溃疡（n=4；5.3%）。没有疱疹性病变或感染的报告。结论：T-VEC具有良好的耐受性和临床应用价值。

引用次数: 20

The neurotoxic effects of immune checkpoint inhibitor therapy for melanoma. 免疫检查点抑制剂治疗黑色素瘤的神经毒性作用。

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-05-31 DOI: 10.2217/mmt-2019-0001

Lavinia Spain, Rachel Wong

The advent of immune checkpoint inhibitors (ICIs), CTLA-4, PD-1 and PD-L1 inhibitors, have dramatically changed outcomes for patients with melanoma and other malignancies [1–3]. With this new class of antineoplastic agents comes a new range of adverse effects. These immune-related adverse events (irAEs) mediated by Tlymphocytes and other mechanisms including enhanced cytokine levels and antibodies [4] are often unpredictable, in contrast to adverse effects seen commonly with cytotoxic chemotherapy. Few of the initial Phase III trials evaluating the role of ICIs in the treatment of melanoma specifically reported immune-related neurotoxicity. When reported, the incidence of grade 3/4 neurotoxicity was low (<2%) [5]. Increasingly, immune-mediated neurological irAEs are being recognized and reported. Clinical presentation is varied and, while usually occurs early on in the course of therapy, in some cases neurological irAEs may occur many months after cessation of ICI therapy [6,7]. Importantly, the morbidity and mortality associated with this toxicity is relatively high. In a series of 613 fatal ICI-associated toxic events reported by Wang et al., 11% of these were attributed to neurological irAEs [8]. A review by Cuzzubbo et al. of neurological irAEs suggests that their incidence is higher with combination CTLA-4/PD-1 inhibition than for either class of agent when used as monotherapy. Interestingly, for monotherapy regimens, the reported rates of any grade neurotoxicity were higher for PD-1 inhibitors compared with CTLA4 inhibitors (anti-CTLA-4 3.8%, anti-PD-1 6.1%, combination therapy 13%). Severe (Grade 3 or 4) irAEs were infrequent, but more common with anti-CTLA-4 (0.7%) than anti-PD1 agents (0.4%). The majority of cases presented early with a median time to onset of 6 weeks [9]. These data are supported by other ‘real-world’ single-center retrospective series of patients treated with anti-CTLA-4 and/or anti-PD1 inhibitors [6] or anti-PD-1 inhibitors alone [10], reporting rates of neurological irAEs of 2.8 and 2.9%, respectively. In the former series, 14% of patients receiving combination therapy had neurological irAEs. In all three series, the clinical presentations were varied, highlighting the need for clinical vigilance when assessing patients for suspected irAEs.

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引用次数: 2

Patient-specific dendritic cell vaccines with autologous tumor antigens in 72 patients with metastatic melanoma 具有自体肿瘤抗原的患者特异性树突状细胞疫苗治疗72例转移性黑色素瘤

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-05-31 DOI: 10.2217/mmt-2018-0010

R. Dillman, A. Cornforth, E. McClay, C. Depriest

Aim: Metastatic melanoma patients were treated with patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines. Patients & methods: A total of 72 patients were enrolled in a single-arm Phase I/II (NCT00948480) trial or a randomized Phase II (NCT00436930). Results: Toxicity was minimal. Median overall survival (OS) was 49.4 months; 5-year OS 46%. A 5-year OS was 72% for 18 recurrent stage 3 without measurable disease when treated and 53% for 30 stage 4 without measurable disease when treated. A total of 24 patients with measurable stage 4 when treated (median of four prior therapies) had an 18.5 months median OS and 46% 2-year OS. Conclusion: This dendritic cell vaccine was associated with encouraging survival in all three clinical subsets. Clinicaltrial.gov NCT00436930 and NCT00948480.

目的：用患者特异性疫苗治疗转移性黑色素瘤患者，该疫苗由自体树突状细胞组成，该细胞负载来自短期自体肿瘤细胞系的辐照细胞的抗原。患者和方法：共有72名患者参加了一项单臂I/II期（NCT00948480）试验或一项随机II期试验（NCT00436930）。结果：毒性最小。中位总生存期（OS）为49.4个月；5年OS 46%。18例无可测量疾病的复发性3期患者在治疗时的5年OS为72%，30例无可测疾病的4期患者在处理时的5月OS为53%。共有24名可测量的4期患者在接受治疗时（之前四次治疗的中位数）有18.5个月的中位OS和46%的2年OS。结论：该树突状细胞疫苗可促进所有三个临床亚群的存活。Clinicaltrial.gov NCT00436930和NCT00948480。

引用次数: 9

Re-biopsy of partially sampled thin melanoma impacts sentinel lymph node sampling as well as surgical margins. 部分取样薄黑色素瘤的重新活检影响前哨淋巴结取样和手术边缘。

IF 3.6 Q4 ONCOLOGY

Melanoma Management

Pub Date : 2019-04-26 eCollection Date: 2019-06-01 DOI: 10.2217/mmt-2018-0011

Evan S Weitman, Matthew C Perez, Daniel Lee, Youngchul Kim, William Fulp, Vernon K Sondak, Amod A Sarnaik, Ricardo J Gonzalez, Carl W Cruse, Jane L Messina, Jonathan S Zager

Aim: To assess the impact of re-biopsy on partially sampled melanoma in situ (MIS), atypical melanocytic proliferation (AMP) and thin invasive melanoma.

Materials & methods: We retrospectively identified cases of re-biopsied partially sampled neoplasms initially diagnosed as melanoma in situ, AMP or thin melanoma (Breslow depth ≤0.75 mm).

Results & conclusion: Re-biopsy led to sentinel lymph node biopsy (SLNB) in 18.3% of cases. No patients upstaged from AMP or MIS had a positive SLNB. One out of nine (11.1%) initially diagnosed as a thin melanoma ≤0.75 mm, upstaged with a re-biopsy, had a positive SLNB. After re-biopsy 8.5% underwent an increased surgical margin. Selective re-biopsy of partially sampled melanoma with gross residual disease can increase the accuracy of microstaging and optimize treatment regarding surgical margins and SLNB.

目的：评估重新活检对部分取样原位黑色素瘤（MIS）、非典型黑色素细胞增殖（AMP）和薄侵袭性黑色素瘤的影响。材料与方法：我们回顾性地确定了一些重新活检的部分取样肿瘤，最初诊断为原位黑色素瘤、AMP或薄黑色素瘤（Breslow深度≤0.75 mm）。结果与结论：18.3%的病例重新活检导致前哨淋巴结活组织检查（SLNB）。从AMP或MIS中抢出来的患者没有SLNB阳性。九分之一（11.1%）最初诊断为≤0.75 mm的薄黑色素瘤，经重新活检后，SLNB呈阳性。再次活检后，8.5%的患者手术切缘增加。对部分采样的伴有严重残留疾病的黑色素瘤进行选择性重新活检可以提高显微分期的准确性，并优化手术边缘和SLNB的治疗。

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