Summary
Background
Taxanes are the current first‐line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or ...comorbidity. However, no effective second‐line therapy for such patients has been established.
Methods
We designed a single‐arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m−2 on days 1 and 8 in a 21‐day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression‐free survival (PFS) and toxicity assessment.
Results
We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference.
Conclusions
ERB showed a promising RR and is a potential candidate for second‐line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients.
What is already known about this topic?
Taxanes are the current first‐line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity.
No effective therapy for taxane‐resistant CAS has been established thus far.
Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes.
What does this study add?
In our single‐arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression‐free survival were 8·6 and 3·0 months, respectively.
Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively.
Although 16 grade 3/4 severe adverse events occurred, all patients recovered.
Eribulin showed a promising response rate and is a potential candidate for second‐line treatment in CAS after taxane treatment.
Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797–798.
What is already known about this topic?
Taxanes are the current first‐line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity.
No effective therapy for taxane‐resistant CAS has been established thus far.
Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes.
What does this study add?
In our single‐arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression‐free survival were 8·6 and 3·0 months, respectively.
Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively.
Although 16 grade 3/4 severe adverse events occurred, all patients recovered.
Eribulin showed a promising response rate and is a potential candidate for second‐line treatment in CAS after taxane treatment.
Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797–798.
Summary
Background
Extramammary Paget disease (EMPD) is a skin adenocarcinoma of apocrine gland origin, in which Paget cells express receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) ...and matrix metalloproteinase (MMP)‐7, and release soluble (s)RANKL into the tumour microenvironment. We previously reported that about 60% of the RANK+ cells among the stromal cells are M2 macrophages, but the identity of the remaining population of RANK+ cells is still unknown.
Objectives
To investigate the unknown subpopulation of RANK‐expressing cells in EMPD.
Methods
The main population of RANK‐expressing cells in the epidermis was composed of epidermal Langerhans cells (LCs). To explore the effects of RANKL on LCs, we stimulated LCs generated from human CD34+ hematopoietic progenitor cells with graded concentrations of sRANKL. To further examine the correlation between LCs and regulatory T cells (Tregs) in EMPD, we employed immunohistochemical staining.
Results
sRANKL stimulation was shown to augment the production of C‐C motif chemokine ligand 17 (CCL17) from LCs. We additionally demonstrated CCL17 expression by CD1a+ LCs in EMPD in an immunofluorescence study. Spearman's rank correlation test confirmed a correlation between the number of LCs and the number of Foxp3+ Tregs in the lesional skin of invasive EMPD. In addition, the numbers of Foxp3+ Tregs in the sentinel lymph nodes of metastatic EMPD were significantly higher than those of metastatic melanoma, which did not express RANKL.
Conclusions
The findings suggest that the RANKL/RANK pathway in EMPD might contribute to the recruitment of Tregs and to maintenance of the tumour microenvironment.
What's already known about this topic?
Receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulates RANK on Langerhans cells (LCs), leading to ultraviolet‐induced cutaneous immunosuppression.
Paget cells express RANKL and matrix metalloproteinase‐7, and release soluble (s)RANKL into the tumour microenvironment.
About 60% of RANK+ cells in stromal cells in extramammary Paget disease (EMPD) are M2 macrophages, and produce C‐C motif chemokine ligand 17 (CCL17) to recruit regulatory T cells (Tregs).
Substantial numbers of Foxp3+ Tregs are observed in lesional skin of EMPD.
What does this study add?
The main population of RANK‐expressing cells in the epidermis was epidermal LCs. sRANKL stimulation augmented the production of CCL17 from human CD34+ haematopoietic progenitor cell‐derived LCs.
An immunofluorescence study showed that CD1a+ LCs in EMPD expressed CCL17.
Immunohistochemical staining revealed a correlation between the number of LCs and the number of Foxp3+ Tregs in the lesional skin of invasive EMPD.
What is the translational message?
A possible role for RANK/RANKL signalling in induction of the immunosuppressive microenvironment of EMPD suggested that targeting of RANKL with denosumab might be used in conjunction with the therapeutic elimination of primary invasive EMPD to prevent local immunosuppression and metastatic disease.
Linked Comment: Fletcher and Haniffa. Br J Dermatol 2017; 176:293–294.
Summary
Cutaneous angiosarcoma (CAS) is a highly aggressive vascular tumour that recurs locally and metastasizes early. Although chemoradiotherapy with taxanes shows a high response rate with ...prolonged survival, second‐line therapy for advanced CAS remains contentious. This report describes three patients with advanced CAS treated with eribulin. In addition, we investigated serum soluble (s)CD163, chemokine (C‐X‐C motif) ligand 10 (CXCL10) and chemokine (C‐C motif) ligand 2 levels at several time points of tumour progression in these patients, revealing serum levels of sCD163 and CXCL10 as potential biomarkers for progression of CAS.
What's already known about this topic?
Two previous case reports suggested the efficacy of eribulin against cutaneous angiosarcoma (CAS).
What does this study add?
Three cases of patients with advanced CAS treated with eribulin.
We investigated serum soluble (s)CD163, chemokine (C‐X‐C motif) ligand 10 (CXCL10) and chemokine (C‐C motif) ligand 2 at several time points of tumour progression in these patients, revealing serum levels of sCD163 and CXCL10 as potential biomarkers for progression of CAS.
Linked Comment: Hata. Br J Dermatol 2018; 179:1246.
Combination of high-resolution C-arm CT and novel metal artifact reduction software may contribute to the assessment of aneurysms treated with stent-assisted coil embolization. This study aimed to ...evaluate the efficacy of a novel Metal Artifact Reduction prototype software combined with the currently available high spatial-resolution C-arm CT prototype implementation by using an experimental aneurysm model treated with stent-assisted coil embolization.
Eight experimental aneurysms were created in 6 swine. Coil embolization of each aneurysm was performed by using a stent-assisted technique. High-resolution C-arm CT with intra-arterial contrast injection was performed immediately after the treatment. The obtained images were processed with Metal Artifact Reduction. Five neurointerventional specialists reviewed the image quality before and after Metal Artifact Reduction. Observational and quantitative analyses (via image analysis software) were performed.
Every aneurysm was successfully created and treated with stent-assisted coil embolization. Before Metal Artifact Reduction, coil loops protruding through the stent lumen were not visualized due to the prominent metal artifacts produced by the coils. These became visible after Metal Artifact Reduction processing. Contrast filling in the residual aneurysm was also visualized after Metal Artifact Reduction in every aneurysm. Both the observational (P < .0001) and quantitative (P < .001) analyses showed significant reduction of the metal artifacts after application of the Metal Artifact Reduction prototype software.
The combination of high-resolution C-arm CT and Metal Artifact Reduction enables differentiation of the coil mass, stent, and contrast material on the same image by significantly reducing the metal artifacts produced by the platinum coils. This novel image technique may improve the assessment of aneurysms treated with stent-assisted coil embolization.
To investigate electrically-active deep levels in high-resistivity single-crystalline diamond, particle-induced charge transient spectroscopy (QTS) techniques were performed using 5.5MeV alpha ...particles and 9MeV carbon focused microprobes. For unintentionally-doped (UID) chemical vapor deposition (CVD) diamond, deep levels with activation energies of 0.35eV and 0.43eV were detected which correspond to the activation energy of boron acceptors in diamond. The results suggested that alpha particle and heavy ion induced QTS techniques are the promising candidate for in-situ investigation of deep levels in high-resistivity semiconductors.
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