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4.
JAMA Dermatol ; 160(3): 303-311, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324293

RESUMO

Importance: The development of artificial intelligence (AI)-based melanoma classifiers typically calls for large, centralized datasets, requiring hospitals to give away their patient data, which raises serious privacy concerns. To address this concern, decentralized federated learning has been proposed, where classifier development is distributed across hospitals. Objective: To investigate whether a more privacy-preserving federated learning approach can achieve comparable diagnostic performance to a classical centralized (ie, single-model) and ensemble learning approach for AI-based melanoma diagnostics. Design, Setting, and Participants: This multicentric, single-arm diagnostic study developed a federated model for melanoma-nevus classification using histopathological whole-slide images prospectively acquired at 6 German university hospitals between April 2021 and February 2023 and benchmarked it using both a holdout and an external test dataset. Data analysis was performed from February to April 2023. Exposures: All whole-slide images were retrospectively analyzed by an AI-based classifier without influencing routine clinical care. Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) served as the primary end point for evaluating the diagnostic performance. Secondary end points included balanced accuracy, sensitivity, and specificity. Results: The study included 1025 whole-slide images of clinically melanoma-suspicious skin lesions from 923 patients, consisting of 388 histopathologically confirmed invasive melanomas and 637 nevi. The median (range) age at diagnosis was 58 (18-95) years for the training set, 57 (18-93) years for the holdout test dataset, and 61 (18-95) years for the external test dataset; the median (range) Breslow thickness was 0.70 (0.10-34.00) mm, 0.70 (0.20-14.40) mm, and 0.80 (0.30-20.00) mm, respectively. The federated approach (0.8579; 95% CI, 0.7693-0.9299) performed significantly worse than the classical centralized approach (0.9024; 95% CI, 0.8379-0.9565) in terms of AUROC on a holdout test dataset (pairwise Wilcoxon signed-rank, P < .001) but performed significantly better (0.9126; 95% CI, 0.8810-0.9412) than the classical centralized approach (0.9045; 95% CI, 0.8701-0.9331) on an external test dataset (pairwise Wilcoxon signed-rank, P < .001). Notably, the federated approach performed significantly worse than the ensemble approach on both the holdout (0.8867; 95% CI, 0.8103-0.9481) and external test dataset (0.9227; 95% CI, 0.8941-0.9479). Conclusions and Relevance: The findings of this diagnostic study suggest that federated learning is a viable approach for the binary classification of invasive melanomas and nevi on a clinically representative distributed dataset. Federated learning can improve privacy protection in AI-based melanoma diagnostics while simultaneously promoting collaboration across institutions and countries. Moreover, it may have the potential to be extended to other image classification tasks in digital cancer histopathology and beyond.


Assuntos
Dermatologia , Melanoma , Nevo , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico , Inteligência Artificial , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Nevo/diagnóstico
6.
Nat Commun ; 15(1): 524, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225244

RESUMO

Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists' decisions has not yet been evaluated. Building upon previous research, we introduce an XAI system that provides precise and domain-specific explanations alongside its differential diagnoses of melanomas and nevi. Through a three-phase study, we assess its impact on dermatologists' diagnostic accuracy, diagnostic confidence, and trust in the XAI-support. Our results show strong alignment between XAI and dermatologist explanations. We also show that dermatologists' confidence in their diagnoses, and their trust in the support system significantly increase with XAI compared to conventional AI. This study highlights dermatologists' willingness to adopt such XAI systems, promoting future use in the clinic.


Assuntos
Melanoma , Confiança , Humanos , Inteligência Artificial , Dermatologistas , Melanoma/diagnóstico , Diagnóstico Diferencial
7.
Dermatologie (Heidelb) ; 74(10): 787-792, 2023 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-37407876

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy that derives from precursors of plasmacytoid dendritic cells and is characterized by disseminated, erythematous or bluish-livid plaques or nodi. Because of the disease's rarity the diagnosis and treatment still pose a significant challenge. We present a case of a patient with BPDCN and show clinical and diagnostic characteristics as well as potential treatment regimes.


Assuntos
Neoplasias Hematológicas , Neoplasias Cutâneas , Humanos , Neoplasias Hematológicas/complicações , Neoplasias Cutâneas/diagnóstico , Células Dendríticas/patologia , Doença Aguda , Palidez/complicações
8.
Eur J Cancer ; 173: 307-316, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35973360

RESUMO

BACKGROUND: Image-based cancer classifiers suffer from a variety of problems which negatively affect their performance. For example, variation in image brightness or different cameras can already suffice to diminish performance. Ensemble solutions, where multiple model predictions are combined into one, can improve these problems. However, ensembles are computationally intensive and less transparent to practitioners than single model solutions. Constructing model soups, by averaging the weights of multiple models into a single model, could circumvent these limitations while still improving performance. OBJECTIVE: To investigate the performance of model soups for a dermoscopic melanoma-nevus skin cancer classification task with respect to (1) generalisation to images from other clinics, (2) robustness against small image changes and (3) calibration such that the confidences correspond closely to the actual predictive uncertainties. METHODS: We construct model soups by fine-tuning pre-trained models on seven different image resolutions and subsequently averaging their weights. Performance is evaluated on a multi-source dataset including holdout and external components. RESULTS: We find that model soups improve generalisation and calibration on the external component while maintaining performance on the holdout component. For robustness, we observe performance improvements for pertubated test images, while the performance on corrupted test images remains on par. CONCLUSIONS: Overall, souping for skin cancer classifiers has a positive effect on generalisation, robustness and calibration. It is easy for practitioners to implement and by combining multiple models into a single model, complexity is reduced. This could be an important factor in achieving clinical applicability, as less complexity generally means more transparency.


Assuntos
Melanoma , Neoplasias Cutâneas , Dermoscopia/métodos , Humanos , Melanoma/diagnóstico por imagem , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico por imagem , Melanoma Maligno Cutâneo
9.
Hautarzt ; 73(4): 298-302, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-34170334

RESUMO

Laugier-Hunziker syndrome (LHS) is characterized by lentiginous hyperpigmentation of the oral mucosa and lips. In addition, longitudinal melanonychia and palmoplantar hyperpigmented lesions may occur. LHS is a clinical diagnosis of exclusion. Herein, we report the case of a 66-year-old woman with LHS. The clinical and histopathologic features of LHS are presented and important differential diagnoses are discussed.


Assuntos
Hiperpigmentação , Doenças Labiais , Doenças da Unha , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Hiperpigmentação/diagnóstico , Hiperpigmentação/patologia , Doenças Labiais/diagnóstico , Mucosa Bucal/patologia , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Síndrome
10.
Oncotarget ; 7(9): 9876-89, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26848524

RESUMO

PURPOSE: Receptor tyrosine kinase AXL (RTK-AXL) is regarded as suitable target in glioma therapy. Here we evaluate the anti-tumoral effect of small molecule inhibitor BMS-777607 targeting RTK-AXL in a preclinical glioma model and provide evidence that RTK-AXL is expressed and phosphorylated in primary and recurrent glioblastoma multiforme (GBM). EXPERIMENTAL DESIGN: We studied the impact of BMS-777607 targeting RTK-AXL in GBM models in vitro and in vivo utilizing glioma cells SF126 and U118MG. Impact on proliferation, apoptosis and angiogenesis was investigated by immunohistochemistry (IHC) and functional assays in vitro and in vivo. Tumor growth was assessed with MRI. Human GBM tissue was analyzed in terms of RTK-AXL phosphorylation by immunoprecipitation and immunohistochemistry. RESULTS: BMS-777607 displayed various anti-cancer effects dependent on increased apoptosis, decreased proliferation and migration in vitro and ex vivo in SF126 and U118 GBM cells. In vivo we observed a 56% tumor volume reduction in SF126 xenografts and remission in U118MG xenografts of more than 91%. The tube formation assay confirmed the anti-angiogenic effect of BMS-777607, which became also apparent in tumor xenografts. IHC of human GBM tissue localized phosphorylated RTK-AXL in hypercellular tumor regions, the migratory front of tumor cells in pseudo-palisades, and in vascular proliferates within the tumor. We further proved RTK-AXL phosphorylation in primary and recurrent disease state. CONCLUSION: Collectively, these data strongly suggest that targeting RTK-AXL with BMS-777607 could represent a novel and potent regimen for the treatment of primary and recurrent GBM.


Assuntos
Aminopiridinas/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Piridonas/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Imuno-Histoquímica , Camundongos Nus , Microscopia de Fluorescência , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor Tirosina Quinase Axl
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