Abstract:
:Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8-15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9-13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6-6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30-0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2-8.5), 5.7 months (95% CI: 3.0-8.4) for dabrafenib, and 3.6 months (95% CI: 3.5-3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
Geukes Foppen MH,Boogerd W,Blank CU,van Thienen JV,Haanen JB,Brandsma Ddoi
10.1097/CMR.0000000000000429subject
Has Abstractpub_date
2018-04-01 00:00:00pages
126-133issue
2eissn
0960-8931issn
1473-5636journal_volume
28pub_type
杂志文章abstract::Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000214
更新日期:2016-02-01 00:00:00
abstract::In this study we compared the strength of the association of constitutional factors and sun exposure with cutaneous malignant melanoma (CMM) and basal cell carcinoma (BCC). We analysed 260 incident cases of CMM, 425 incident cases of BCC and two sets of population controls from previous case-control studies conducted ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199812000-00013
更新日期:1998-12-01 00:00:00
abstract::BRAF mutations are found in ~50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAF-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutati...
journal_title:Melanoma research
pub_type: 杂志文章,多中心研究
doi:10.1097/CMR.0000000000000398
更新日期:2017-12-01 00:00:00
abstract::Violacein is the main pigment produced by Chromobacterium violaceum, a saprophytic gram-negative bacillus. Violacein is formed by the condensation of two modified tryptophan molecules and has potential anti-neoplastic effects. The purpose of this pilot study was to investigate the in vitro activity of violacein in hum...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200410000-00014
更新日期:2004-10-01 00:00:00
abstract::Cell clones derived from a human melanoma metastasis selected for different integrin profiles were examined in vitro for invasive potential and biological and biochemical features potentially related to this process. Clones which expressed high levels of integrins showed high invasive potential, extracellular matrix d...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199212000-00012
更新日期:1992-12-01 00:00:00
abstract::Mucosal melanoma of the nasal cavity and paranasal sinus is always associated with poor prognosis, and 5-year overall survival does not exceed 40%. Our study aimed to compare the intraoperative conditions and prognosis of different surgical techniques to determine the optimum surgical approach for patients with mucosa...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000516
更新日期:2019-02-01 00:00:00
abstract::Paraffin-embedded tissue from the primary tumours of 116 patients with malignant melanoma, and in 40 cases also from corresponding metastases, were examined for accumulation of p53 protein. The fraction of tumours with positive p53 immunostaining was 13% in the least invasive and 36% in the most invasive primary lesio...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199506000-00007
更新日期:1995-06-01 00:00:00
abstract::Dissemination of uveal melanomas is almost exclusively haematogenous, making angiogenesis of the tumour a prerequisite for the formation of metastases. Uveal melanomas must employ strategies to evade the immune system in order to escape immune surveillance. We therefore determined the expression of the following angio...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199910000-00003
更新日期:1999-10-01 00:00:00
abstract::The mechanism of action of fotemustine, a relatively new chloroethylnitrosourea, was evaluated in human melanoma cells in order to assess its potential as an agent for hyperthermic limb perfusion. Fotemustine was more toxic to O6-alkylguanine methyl transferase (AGT) deficient (Mer-) cells than Mer+ cells, implicating...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199802000-00012
更新日期:1998-02-01 00:00:00
abstract::Ninety primary melanoma patients were studied to investigate the importance of adopting the simultaneous use of patent blue dye (PBD) and lymphoscintigraphy plus gamma detection probe to locate the sentinel node (SN). In total 135 SNs in 105 basins were visualized preoperatively under a gamma camera after lymphoscinti...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199912000-00008
更新日期:1999-12-01 00:00:00
abstract::Ultraviolet-B (UV-B) triggers a cascade of events involving cell cycle control genes leading ultimately to DNA repair or apoptosis. The hypothesis examined here is that the genetic abnormality predisposing to melanoma affects the ability of the cell to respond appropriately to UV-B, so favouring mutagenesis. Epstein-B...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200102000-00001
更新日期:2001-02-01 00:00:00
abstract::Immune-checkpoint inhibitors (ICIs) exposed the oncology community to novel immune-related adverse events (irAEs). Here, we report on a retrospective analysis of patients with melanoma who developed an ICI-related, unilateral, acute and peripheral facial nerve paralysis (Bell's palsy).We retrospectively reviewed all t...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000715
更新日期:2021-01-22 00:00:00
abstract::The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition i...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000174
更新日期:2015-10-01 00:00:00
abstract::In the present study, we constructed a pEgr-tumour necrosis factor-alpha (TNFalpha) plasmid and investigated its expression properties in B16 cells on exposure to ionizing irradiation and, furthermore, the effect of gene radiotherapy on a melanoma model. Firstly, the recombinant pEgr-TNFalpha plasmid was constructed a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200506000-00007
更新日期:2005-06-01 00:00:00
abstract::When cancer cells, including melanoma cells, are genetically altered to secrete cytokines, irradiated and injected into subjects, long-term antitumour immunity is induced. Optimally, existing melanomas induced to produce cytokines in vivo could stimulate this same immune response. Although in vivo electroporation enha...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200012000-00010
更新日期:2000-12-01 00:00:00
abstract::Several hypotheses have explicitly implicated the role of an altered redox status of melanin in the aetiology of melanoma and macular degeneration. The balance between the intrinsic anti-oxidant and pro-oxidant properties of melanin is lost, resulting in an altered redox phenotype. We propose that such an alteration o...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/01.cmr.0000195699.35143.df
更新日期:2006-02-01 00:00:00
abstract::M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was carried out to investigate the serum levels of M30 and M65 in patients with melanoma and the relationship with tumor progression and known prognostic parameters. Fifty-...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328363e4ab
更新日期:2013-10-01 00:00:00
abstract::Proteomics provides a powerful approach for screening alterations in protein expression and post-translational modification associated with particular human diseases. In this study, the analysis of protein expression was focused on malignant melanoma in order to determine the candidate genes involved in tumour progres...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200508000-00002
更新日期:2005-08-01 00:00:00
abstract::The National Comprehensive Cancer Network has formulated guidelines for the management of cutaneous malignant melanoma with regard to resection margins (RMs) and regional staging. The aim of this study was to assess compliance with these recommendations in the general population of the USA. The Surveillance, Epidemiol...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32836254bd
更新日期:2013-08-01 00:00:00
abstract::In human melanoma no complete information about the expression of the apoptosis-promoting and apoptosis-inhibiting members of the Bcl-2 family has been available to date. In this study we have investigated by Western blotting the expression pattern of Bcl-2 and its homologues Bax, Bak, Bcl-xL, Bcl-xS, Mcl-1 and Bad in...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199806000-00001
更新日期:1998-06-01 00:00:00
abstract::The cholesterol-lowering medications, statins, inhibit cellular proliferation and induce apoptosis in an array of cancer cell lines, including melanoma. We investigated the apoptotic mechanism of lovastatin on human melanoma cell lines in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell T...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200504000-00001
更新日期:2005-04-01 00:00:00
abstract::Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed up after treatment of germ cell tumours (GCTs) who were referred to the dermatologist for multiple ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200104000-00005
更新日期:2001-04-01 00:00:00
abstract::For primary melanoma, there is a delay between the initial skin biopsy and sentinel lymph node dissection, which may cause anxiety for the patient. The consequences of this delay on disease progression are unknown. The goal of this study was to determine whether delay time for sentinel node dissection from the initial...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835861f6
更新日期:2012-10-01 00:00:00
abstract::Checkpoint inhibitor immunotherapy is a transformative treatment for advanced malignancies, but can be associated with numerous immune-related adverse events (irAEs). The majority of irAEs include those that closely resemble known cutaneous and neurocutaneous autoimmune or autoinflammatory diseases, such as scleroderm...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000642
更新日期:2020-06-01 00:00:00
abstract::The proto-oncogene c-Kit encodes a membrane receptor protein with intrinsic tyrosine kinase activity. Activation of c-Kit induces cell proliferation, differentiation or migration among different cell types. The present study provides evidence that c-Kit plays an important role in the cell differentiation rather than i...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199510000-00002
更新日期:1995-10-01 00:00:00
abstract::Between 1983 and 1990, 59 patients with malignant melanoma were retrospectively reviewed to assess the safety, efficacy and the maximal tolerated dose of cisplatin used in hyperthermic isolated limb perfusion. The median follow-up was 29 months (range 3-54 months). The local recurrence rate was 12% in Stage I, 33% in ...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章
doi:10.1097/00008390-199104000-00007
更新日期:1991-04-01 00:00:00
abstract::The concept of 'vasculogenic mimicry' (VM) was introduced to describe the unique ability of highly invasive tumor cells to form capillary-like structures (CLS) and matrix-rich patterned network in three-dimensional culture that mimic embryonic vasculogenic network. Recently, we have shown that CLS formation requires a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3282f1d2ec
更新日期:2007-12-01 00:00:00
abstract::The presence of substantial amounts of GM3 ganglioside on human melanomas and other tumours, together with its peculiar biological properties, makes this glycolipid a unique target for cancer immunotherapy. B16 mouse melanoma expresses GM3 and constitutes an appropriate model for the development of novel GM3-based vac...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200106000-00003
更新日期:2001-06-01 00:00:00
abstract::Prognostic groups defined by lactate dehydrogenase concentration and number of organ sites containing metastases have been reported for patients treated with dabrafenib and trametinib for advanced melanoma. We aimed to validate these prognostic groups for patients treated with vemurafenib and cobimetinib in the coBRIM...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000634
更新日期:2020-06-01 00:00:00
abstract::Preoperative assessment of melanoma invasion by sonometry has been reported to exhibit a high correlation with postoperative histometry based on the determination of a regression coefficient. We believe that this approach is not adequate and that it can be misleading. We therefore applied an appropriate statistical ap...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199610000-00007
更新日期:1996-10-01 00:00:00