Subject(s)
Antibodies, Monoclonal , Miliaria , Humans , Antibodies, Monoclonal/adverse effects , Apoptosis , KeratinocytesABSTRACT
CeTe3 is a unique platform to investigate the itinerant magnetism in a van der Waals (vdW) coupled metal. Despite chemical pressure being a promising route to boost quantum fluctuation in this system, a systematic study on the chemical pressure effect on Ce3+(4f1) states is absent. Here, we report on the successful growth of a series of Se doped single crystals of CeTe3. We found a fluctuation driven exotic magnetic rotation from the usual easy-axis ordering to an unusual hard-axis ordering. Unlike in localized magnetic systems, near-critical magnetism can increase itinerancy hand-in-hand with enhancing fluctuation of magnetism. Thus, seemingly unstable hard-axis ordering emerges through kinetic energy gain, with the self-consistent observation of enhanced magnetic fluctuation (disorder). As far as we recognize, this order-by-disorder process in fermionic system is observed for the first time within vdW materials. Our finding opens a unique experimental platform for direct visualization of the rich quasiparticle Fermi surface deformation associated with the Fermionic order-by-disorder process. Also, the search for emergent exotic phases by further tuning of quantum fluctuation is suggested as a promising future challenge.
ABSTRACT
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.
Subject(s)
Breast Neoplasms , Hemangiosarcoma , Aged , Breast Neoplasms/drug therapy , Bridged-Ring Compounds , Furans , Hemangiosarcoma/drug therapy , Humans , Ketones , Taxoids , Treatment OutcomeABSTRACT
BACKGROUND: Surgery is the gold standard for basal cell carcinomas (BCC). Current recommended surgical margins for BCCs are determined from studies in Caucasian populations. However, the appropriate surgical margins for BCCs in non-white races are unclear. OBJECTIVES: To investigate the accuracy of preoperative determination of clinical tumour borders and appropriate surgical margins in Japanese patients with BCC. METHODS: The maximum calculated differences in distance between the preoperatively determined surgical margins and the actual histologic tumour side margins were considered as 'accuracy gaps' of clinical tumour borders. Estimated side margin positivity rates (ESMPRs) with narrower (2 and 3 mm) surgical margins were calculated on the basis of the accuracy gaps. RESULTS: Overall, 1000 surgically excised BCCs from 980 Japanese patients were included. The most frequent histologic subtype was nodular BCC (67%). The median accuracy gap was 0.3 mm [interquartile range (IQR): -0.5 to +1 mm]. The ESMPRs with 2- and 3-mm surgical margins were 3.8% and 1.4%, respectively. Only the ESMPRs between the well-defined (n = 921) and poorly defined clinical tumour border groups (n = 79) showed statistical difference [2-mm margin: 3.1% vs. 11.7%, OR: 3.89, 95% confidential interval (CI): 1.41-10.71, P <0.01; 3-mm margin: 0.97% vs. 6.3%, OR: 6.58, 95% CI: 1.67-25.99, P <0.01]. No significant differences in ESMPRs were noted in other subgroups including risk classifications. CONCLUSIONS: The determined clinical tumour border accuracy gaps in this Japanese cohort were negligible. Dermatologic surgeons may use narrower surgical margins with acceptable margin positivity rates. The clarity of clinical tumour borders could be an appropriate guide for selection of different surgical margins in the Japanese cohort.
Subject(s)
Carcinoma, Basal Cell , Skin Neoplasms , Carcinoma, Basal Cell/surgery , Humans , Japan , Margins of Excision , Retrospective Studies , Skin Neoplasms/surgerySubject(s)
B7-H1 Antigen/metabolism , Hutchinson's Melanotic Freckle/metabolism , Melanoma/metabolism , Skin Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Japan , Male , Middle Aged , Mucous Membrane/metabolism , Retrospective Studies , Young Adult , Melanoma, Cutaneous MalignantSubject(s)
Carboxy-Lyases/genetics , Eczema/genetics , Hypohidrosis/genetics , Myopathies, Structural, Congenital/diagnosis , ORAI1 Protein/genetics , Biopsy , Child, Preschool , DNA Mutational Analysis , Dermoscopy , Eczema/pathology , Humans , Hypohidrosis/pathology , Male , Muscle, Skeletal/pathology , Myopathies, Structural, Congenital/complications , Myopathies, Structural, Congenital/genetics , Myopathies, Structural, Congenital/pathology , Skin/diagnostic imaging , Skin/pathology , Sweat Glands/pathologySubject(s)
Antineoplastic Agents/administration & dosage , Docetaxel/administration & dosage , Paget Disease, Extramammary/drug therapy , Palliative Care/methods , Skin Neoplasms/drug therapy , Administration, Cutaneous , Aged , Aged, 80 and over , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Neoplasm Staging , Paget Disease, Extramammary/mortality , Paget Disease, Extramammary/pathology , Progression-Free Survival , Retrospective Studies , Skin Neoplasms/mortality , Skin Neoplasms/pathologySubject(s)
Antigens, CD/metabolism , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/pathology , Integrin alpha Chains/metabolism , Skin Neoplasms/pathology , T-Lymphocytes, Regulatory/metabolism , Carcinoma, Basal Cell/immunology , Carcinoma, Squamous Cell/immunology , Humans , Immunologic Memory , Skin/immunology , Skin Neoplasms/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/pathology , Tumor MicroenvironmentSubject(s)
CD8-Positive T-Lymphocytes/immunology , Immunologic Memory , Interleukin-17/metabolism , Psoriasis/immunology , Skin/pathology , CD8-Positive T-Lymphocytes/metabolism , Cell Separation , Cells, Cultured , Flow Cytometry , Humans , Interferon-gamma/metabolism , Interleukin-17/immunology , Primary Cell Culture , Psoriasis/pathology , Skin/cytology , Skin/immunology , Time FactorsSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Skin Neoplasms/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Feasibility Studies , Humans , Kaplan-Meier Estimate , Neoplasm Staging , Prognosis , Progression-Free Survival , Radiotherapy Dosage , Retrospective Studies , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival RateABSTRACT
BACKGROUND: Application of deep-learning technology to skin cancer classification can potentially improve the sensitivity and specificity of skin cancer screening, but the number of training images required for such a system is thought to be extremely large. OBJECTIVES: To determine whether deep-learning technology could be used to develop an efficient skin cancer classification system with a relatively small dataset of clinical images. METHODS: A deep convolutional neural network (DCNN) was trained using a dataset of 4867 clinical images obtained from 1842 patients diagnosed with skin tumours at the University of Tsukuba Hospital from 2003 to 2016. The images consisted of 14 diagnoses, including both malignant and benign conditions. Its performance was tested against 13 board-certified dermatologists and nine dermatology trainees. RESULTS: The overall classification accuracy of the trained DCNN was 76·5%. The DCNN achieved 96·3% sensitivity (correctly classified malignant as malignant) and 89·5% specificity (correctly classified benign as benign). Although the accuracy of malignant or benign classification by the board-certified dermatologists was statistically higher than that of the dermatology trainees (85·3% ± 3·7% and 74·4% ± 6·8%, P < 0·01), the DCNN achieved even greater accuracy, as high as 92·4% ± 2·1% (P < 0·001). CONCLUSIONS: We have developed an efficient skin tumour classifier using a DCNN trained on a relatively small dataset. The DCNN classified images of skin tumours more accurately than board-certified dermatologists. Collectively, the current system may have capabilities for screening purposes in general medical practice, particularly because it requires only a single clinical image for classification.