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Melanoma research
Lippincott Williams And Wilkins
Melanoma research

Lippincott Williams And Wilkins

0960-8931

Melanoma research/Journal Melanoma researchSCIISTP
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    Cardiovascular disease and malignant melanoma

    Wang, Charlie YueZoungas, SophiaVoskoboynik, MarkMar, Victoria...
    7页
    查看更多>>摘要：In the last decade, systemic therapies such as immune checkpoint inhibitors and BRAF-MEK inhibitors have improved the prognosis of high-risk and advanced melanoma. With improved survival, melanoma survivorship is increasingly important, particularly in patients who have a good prognosis or are diagnosed at a younger age. It is increasingly recognized that cancer and its treatment is associated with increased cardiovascular morbidity and mortality. Indeed, data from observational studies and meta-analyses of randomized controls trials in melanoma show that systemic therapies may be associated with cardiac toxicities, such as myocardial infarction, heart failure, myocarditis and stroke. Our review will discuss cardiovascular disease and risk factors in the context of melanoma and outline the importance of cardiovascular risk modification in this population.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Phase II study of apatinib combined with temozolomide in patients with advanced melanoma after failure of immunotherapy

    Zhou, LiYang, YueSi, LuChi, Zhihong...
    8页
    查看更多>>摘要：Treatment for advanced melanoma after progression on immunotherapy is limited. This phase II trial (NCT03422445) was conducted to evaluate the efficacy and safety of apatinib plus temozolomide in patients with advanced melanoma after failure of immunotherapy. Patients with unresectable stage III or stage IV melanoma after progression on immunotherapy were treated with temozolomide 300 mg on days 1-5 and apatinib 500 mg daily every 28-day cycle until disease progression or intolerable toxicities. Besides immunotherapy, prior chemotherapy, targeted therapy, and clinical trials were allowed. The primary endpoint was progression-free survival. Secondary endpoints were objective response rate, disease control rate, overall survival, and safety. Of 29 patients, 28 (96.6%) had metastatic diseases, and the predominant subtypes were mucosal [12 (41.4%)] and acral melanoma [eight (27.6%)]. Five (17.2%) patients showed BRAF, CKIT, or NRAS mutation. Five achieved confirmed partial response, with an objective response rate of 17.2%. The disease control rate was 82.8%. The median progression-free survival was 5.0 months [95% confidence interval (CI): 4.7-5.3], and the median overall survival was 10.1 months (95% CI: 5.1-15.0). Grade 3-4 treatment-related adverse events included proteinuria [four (13.8%)], thrombocytopenia [two (6.9%)], hypertension [one (3.4%)], and hyperbilirubinemia [one (3.4%)]. No treatment-related death occurred. Apatinib plus temozolomide demonstrated promising efficacy and manageable safety profile in patients with advanced melanoma after progression on immunotherapy.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Clinicopathological features and programmed death-ligand 1 immunohistochemical expression in a multicenter cohort of uterine and ovarian melanomas: a retrospective study in Japan (KCOG-G1701s)

    Kobara, HisanoriMatsuura, MotokiTokuyama, OsamuYamawaki, Takaharu...
    9页
    查看更多>>摘要：The objective of this study was to propose prognostic factors and optimal treatment strategies by analyzing the clinicopathological features and programmed death-ligand 1 (PD-L1) expression. We analyzed 31 patients diagnosed with uterine or ovarian melanoma between 1997 and 2017 in the Kansai Clinical Oncology Group/Intergroup. Twenty-four and seven patients with cervical and ovarian melanomas were included, respectively. Immune checkpoint inhibitors were used in seven patients, and the objective response rate was 40%. Notably, two patients with objective responses had a high PD-L1 expression. Ten and four patients with cervical and ovarian melanomas, respectively, had high PD-L1 immunohistochemical expressions. Multivariate analysis revealed that tumor stage was an independent prognostic factor for progression-free survival in patients with cervical melanomas. In patients with ovarian melanomas, the 1-year cumulative progression-free and overall survival rates were 0 and 29%, respectively. Kaplan-Meier analyses revealed that age <60 years was associated with poorer progression-free and overall survivals in patients with ovarian melanomas. In patients with cervical melanomas, the 1-, 3-, and 5-year cumulative overall survival rates were 53, 32, and 16%, respectively. Histological atypia was associated with a poorer progression-free survival, but there was no difference in survival between patients who underwent radical hysterectomy and those who did not. The present study is a large cohort study of uterine and ovarian melanomas, which are aggressive tumors with a significantly poor prognosis, even after standard surgery and adjuvant therapy. The use of immune checkpoint inhibitors is a promising and effective treatment option.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Efficacy and safety of angiogenesis inhibitors in melanoma: a meta-analysis of seven randomized controlled trials

    Fu, Xue-LeiFeng, Li-PingYu, Hai-RongDu, Lin...
    7页
    查看更多>>摘要：Little is known about the efficacy and safety of angiogenesis inhibitor therapy in patients with melanoma. The objective of this study was to assess the possible benefits and harms of angiogenesis inhibitor therapy in patients with melanoma. Electronic databases of PubMed and Web of Science were searched from inception to January 2020. Randomized controlled trials (RCTs) that investigated the efficacy and safety of angiogenesis inhibitor therapy in patients with melanoma were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS), reported as hazard ratios (HRs). Secondary outcomes were disease control, objective response, and adverse events, reported as odds ratios (ORs), and trial sequential analysis (TSA) was also performed. We identified seven trials with 3185 patients. There was no significant difference in OS [HR, 0.99; 95% confidence interval (CI), 0.90-1.09] or PFS (HR, 0.91; 95% CI, 0.83-1.00) between the treatment groups. No significant effect of angiogenesis inhibitor therapy was identified on disease control (OR, 1.23; 95% CI, 0.97-1.55) or objective response (OR, 1.27; 95% CI, 0.99-1.62). TSA showed that the sample size for analysis of disease control was sufficient. Additionally, angiogenesis inhibitor therapy increased risks of hypertension, neurological symptoms, and diarrhea. Angiogenesis inhibitor therapy makes no significant improvement in OS or PFS in patients with melanoma and even causes an increased risk of important adverse events. Therefore, angiogenesis inhibitor therapy is not recommended for the treatment of melanoma.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Long-term control of melanoma adrenal metastasis treated with radiotherapy

    McCann, BrendanHiggins, MartinKok, David L.Hong, Wei...
    7页
    查看更多>>摘要：Melanoma remains a large global burden with a significant proportion of patients succumbing to metastatic disease. The adrenal gland is a common area for metastasis with surgical treatment as the main modality. Radiotherapy is less utilised in this setting with uncertainty over deliverability and efficacy. Here, we present the details and outcomes of 20 patients treated with radiotherapy, with or without systemic therapy, for melanoma adrenal metastasis in a single institute. Twenty patients were identified from radiation treatment and medical records from between 2015 and 2019 at our institution. Three patients had bilateral radiotherapy treatments and therefore 23 adrenal lesions were analysed. Demographics, indications for treatment, radiotherapy methodology and outcomes were recorded. Outcomes were based on serial F-18 FDG PET/computerized tomography scans reporting using the PERCIST criteria. The most common indication for radiotherapy was oligo-progressive disease (70%) followed by symptom palliation. Eight (35%) of the treatments were delivered by stereotactic ablative body radiotherapy. Twelve (60%) patients had concurrent immunotherapy. Twenty of twenty-three (87%) adrenal lesions had an initial response to treatment with 12 (60%) maintaining local control until death or end of follow-up. Median adrenal-specific progression-free survival was 13 months. Four patients (17%) required salvage adrenalectomy. Symptom palliation was achieved in the majority of patients for which it was indicated and there were no grade three toxicities. The median time from radiotherapy to change of immunotherapy treatment was 4 months. Radiotherapy for melanoma adrenal metastasis is effective and deliverable. With the majority of patients achieving a palliative and clinically relevant durable response, adrenalectomy can be reserved as a salvage option.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Real-world data on melanoma brain metastases and survival outcome

    Pedersen, SidselMoller, SorenDonia, MarcoPersson, Gitte Fredberg...
    10页
    查看更多>>摘要：Novel medical therapies have revolutionized outcome for patients with melanoma. However, patients with melanoma brain metastases (MBM) still have poor survival. Data are limited as these patients are generally excluded from clinical trials, wherefore real-world data on clinical outcome may support evidence-based treatment choices for patients with MBM. Patients diagnosed with MBM between 2008 and 2020 were included retrospectively. Patient characteristics, treatment, and outcome data were recorded from The Danish Metastatic Melanoma Database, pathology registries, electronic patient files, and radiation plans. Anti-programmed cell death protein 1 antibodies and the combination of BRAF/MEK-inhibitors were introduced in Denmark in 2015, and the cohort was split accordingly for comparison. A total of 527 patients were identified; 148 underwent surgical excision of MBM, 167 had stereotactic radiosurgery (SRS), 270 received whole-brain radiation therapy (WBRT), and 343 received systemic therapies. Median overall survival (mOS) for patients diagnosed with MBM before and after 2015 was 4.4 and 7.6 months, respectively. Patients receiving surgical excision as first choice of treatment had the best mOS of 10.9 months, whereas patients receiving WBRT had the worst outcome (mOS, 3.4 months). Postoperative SRS did not improve survival or local control after surgical excision of brain metastases. Of the 40 patients alive >3 years after diagnosis of MBM, 80% received immunotherapy at some point after diagnosis. Patients with meningeal carcinosis did not benefit from treatment with CPI. Outcome for patients with MBM has significantly improved after 2015, but long-term survivors are rare. Most patients alive >3 years after diagnosis of MBM received immunotherapy.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    A lead-in safety study followed by a phase 2 clinical trial of dabrafenib, trametinib and hydroxychloroquine in advanced BRAF(V600) mutant melanoma patients previously treated with BRAF-/MEK-inhibitors and immune checkpoint inhibitors

    Awada, GilSchwarze, Julia KatharinaTijtgat, JensFasolino, Giuseppe...
    9页
    查看更多>>摘要：Patients with advanced BRAF(V600) mutant melanoma who progressed on prior treatment with BRAF-/MEK-inhibitors and programmed cell death 1 or cytotoxic T-lymphocyte-associated antigen 4 immune checkpoint inhibitors can benefit from retreatment with the combination of a BRAF- and a MEK-inhibitor ('rechallenge'). Hydroxychloroquine can prevent autophagy-driven resistance and improve the efficacy of BRAF-/MEK-inhibitors in preclinical melanoma models. This clinical trial investigated the use of combined BRAF-/MEK-inhibition with dabrafenib and trametinib plus hydroxychloroquine in patients with advanced BRAF(V600) mutant melanoma who previously progressed on prior treatment with BRAF-/MEK-inhibitors and immune checkpoint inhibitors. Following a safety lead-in phase, patients were randomized in the phase 2 part of the trial between upfront treatment with dabrafenib, trametinib and hydroxychloroquine (experimental arm), or dabrafenib and trametinib, with the possibility to add-on hydroxychloroquine at the time of documented tumor progression (contemporary control arm). Ten and four patients were recruited to the experimental and contemporary control arm, respectively. The objective response rate was 20.0% and the disease control rate was 50.0% in the experimental arm, whereas no responses were observed before or after adding hydroxychloroquine in the contemporary control arm. No new safety signals were observed for dabrafenib and trametinib. Hydroxychloroquine was suspected of causing an anxiety/psychotic disorder in one patient. Based on an early negative evaluation of the risk/benefit ratio for adding hydroxychloroquine to dabrafenib and trametinib when 'rechallenging' BRAF(V600)mutant melanoma patients, recruitment to the trial was closed prematurely.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Robotic CyberKnife radiosurgery for small choroidal melanomas

    Schmelter, ValerieHofmann, TheresaSchneider, FrederickWeber, Constance...
    8页
    查看更多>>摘要：Plaque brachytherapy is the most common procedure for the treatment of small choroidal melanoma, especially in posteriorly located tumors. However, there is only little information on outcome after treatment with stereotactic radiosurgery, for example, CyberKnife radiosurgery. We reviewed patients with choroidal melanoma (maximum tumor height 4 mm) treated with CyberKnife radiosurgery. Demographic information, tumor dimension, complications, metastasis and overall survival during the whole follow-up were tracked and analyzed with a specific focus on local tumor control and potential risk factors. One hundred eighty-eight patients (102 female, 54.2%) with a median age of 63 years [interquartile range (IQR): 54-73 years] were analyzed over a median of 46 months (IQR: 24-62 months). Metastasis occurred in 14 patients (7.4%) in median of 18 months after treatment (IQR: 13-47 months) and survival was achieved in 178 patients (94.7%). Within the observation period, eye retention was observed in 166 patients (88.3%). Superior local control was achieved in patients who received a prescription dose of at least 21 Gy or more (91.6%; P = 0.04). Other potential risk factors incrementing local control were treatment planning with missing MRI in advance and too small target delineation during the planning process. Radiosurgery (CyberKnife) in a single, outpatient procedure is suitable for the treatment of small choroidal melanoma. We found local control rate after 3 years compared to the standard treatment with plaque brachytherapy. On the study side, 15 years of CyberKnife treatment allowed to identify risk factors that might increment local control and thus improve treatment regimens.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Severe treatment-induced inflammatory polyarthritis in advanced melanoma patients: 2 case reports

    Lauwyck, JustineSchreuer, MaxMeric de Bellefon, LaurentVan Erps, Joanna...
    5页
    查看更多>>摘要：Immune checkpoint inhibitors (ICI) and targeted therapies form the therapeutic mainstay for v-Raf murine sarcoma viral oncogene homolog B V600-mutated metastatic melanoma. Both treatment regimens can cause inflammatory arthritis. The reported incidence of treatment-induced inflammatory arthritis is low, though presumably underestimated due to lack of awareness, clear definitions and uniform grading systems. Nevertheless, recognition is important as inflammatory arthritis can become chronic and thus affect the quality of life beyond treatment. In this short communication, we present two patients with metastatic melanoma treated with ICI and targeted therapies who develop severe polyarthritis. Based on their clinical discourse we describe standard inflammatory arthritis treatment modalities and more advanced immunomodulatory treatment options with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Long-term immunosuppressive treatment with glucocorticoids or DMARDs in this setting raises concerns about antitumour response and potential carcinogenic risk. Current literature on this topic is scarce, heterogeneous and retrospective. Prospective analysis of cancer patients treated with DMARDs is needed to clearly address these concerns.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins

    Severe blistering eruptions induced by immune checkpoint inhibitors: a multicentre international study of 32 cases

    Carrera, CristinaElshot, Yannick S.Bensaid, BenoitSegura, Sonia...
    6页
    查看更多>>摘要：Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. To better define the clinical and histological features, treatment, and prognosis of ICI-related severe blistering cutaneous eruptions. This retrospective case series was conducted between 2014/05/15 and 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age >= 18 years old, skin eruption with blisters with detachment covering >= 1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD), or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by four experts in EN or LD/UD. Skin biopsies were blindly reviewed. Thirty-two patients were included. Median time to onset was 52 days (3-420 days). Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, and maximal detachment. Most patients were treated with topical with or without systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending.
      原文链接:
    • NSTL
    • Lippincott Williams & Wilkins