For clear cell renal cell carcinoma (ccRCC) risk-dependent diagnostic and therapeutic algorithms are routinely implemented in clinical practice. Artificial intelligence-based image analysis has the ...potential to improve outcome prediction and thereby risk stratification. Thus, we investigated whether a convolutional neural network (CNN) can extract relevant image features from a representative hematoxylin and eosin-stained slide to predict 5-year overall survival (5y-OS) in ccRCC. The CNN was trained to predict 5y-OS in a binary manner using slides from TCGA and validated using an independent in-house cohort. Multivariable logistic regression was used to combine of the CNNs prediction and clinicopathological parameters. A mean balanced accuracy of 72.0% (standard deviation SD = 7.9%), sensitivity of 72.4% (SD = 10.6%), specificity of 71.7% (SD = 11.9%) and area under receiver operating characteristics curve (AUROC) of 0.75 (SD = 0.07) was achieved on the TCGA training set (n = 254 patients / WSIs) using 10-fold cross-validation. On the external validation cohort (n = 99 patients / WSIs), mean accuracy, sensitivity, specificity and AUROC were 65.5% (95%-confidence interval CI: 62.9–68.1%), 86.2% (95%-CI: 81.8–90.5%), 44.9% (95%-CI: 40.2–49.6%), and 0.70 (95%-CI: 0.69–0.71). A multivariable model including age, tumor stage and metastasis yielded an AUROC of 0.75 on the TCGA cohort. The inclusion of the CNN-based classification (Odds ratio = 4.86, 95%-CI: 2.70–8.75, p < 0.01) raised the AUROC to 0.81. On the validation cohort, both models showed an AUROC of 0.88. In univariable Cox regression, the CNN showed a hazard ratio of 3.69 (95%-CI: 2.60–5.23, p < 0.01) on TCGA and 2.13 (95%-CI: 0.92–4.94, p = 0.08) on external validation. The results demonstrate that the CNN’s image-based prediction of survival is promising and thus this widely applicable technique should be further investigated with the aim of improving existing risk stratification in ccRCC.
The diagnosis of most cancers is made by a board-certified pathologist based on a tissue biopsy under the microscope. Recent research reveals a high discordance between individual pathologists. For ...melanoma, the literature reports on 25–26% of discordance for classifying a benign nevus versus malignant melanoma. A recent study indicated the potential of deep learning to lower these discordances. However, the performance of deep learning in classifying histopathologic melanoma images was never compared directly to human experts. The aim of this study is to perform such a first direct comparison.
A total of 695 lesions were classified by an expert histopathologist in accordance with current guidelines (350 nevi/345 melanoma). Only the haematoxylin & eosin (H&E) slides of these lesions were digitalised via a slide scanner and then randomly cropped. A total of 595 of the resulting images were used to train a convolutional neural network (CNN). The additional 100 H&E image sections were used to test the results of the CNN in comparison to 11 histopathologists. Three combined McNemar tests comparing the results of the CNNs test runs in terms of sensitivity, specificity and accuracy were predefined to test for significance (p < 0.05).
The CNN achieved a mean sensitivity/specificity/accuracy of 76%/60%/68% over 11 test runs. In comparison, the 11 pathologists achieved a mean sensitivity/specificity/accuracy of 51.8%/66.5%/59.2%. Thus, the CNN was significantly (p = 0.016) superior in classifying the cropped images.
With limited image information available, a CNN was able to outperform 11 histopathologists in the classification of histopathological melanoma images and thus shows promise to assist human melanoma diagnoses.
•A convolutional neural network (CNN) was trained with 595 histopathologic images of melanoma and nevi.•In a direct comparison, the CNN and 11 histopathologists classified a test set of 100 additional histopathologic images (1:1 melanoma/nevi).•The CNN systematically outperformed the 11 histopathologists in terms of overall accuracy, sensitivity and specificity (p = 0.016).
In recent months, multiple publications have demonstrated the use of convolutional neural networks (CNN) to classify images of skin cancer as precisely as dermatologists. However, these CNNs failed ...to outperform the International Symposium on Biomedical Imaging (ISBI) 2016 challenge which ranked the average precision for classification of dermoscopic melanoma images. Accordingly, the technical progress represented by these studies is limited. In addition, the available reports are impossible to reproduce, due to incomplete descriptions of training procedures and the use of proprietary image databases or non-disclosure of used images. These factors prevent the comparison of various CNN classifiers in equal terms.
To demonstrate the training of an image-classifier CNN that outperforms the winner of the ISBI 2016 CNNs challenge by using open source images exclusively.
A detailed description of the training procedure is reported while the used images and test sets are disclosed fully, to insure the reproducibility of our work.
Our CNN classifier outperforms all recent attempts to classify the original ISBI 2016 challenge test data (full set of 379 test images), with an average precision of 0.709 (vs. 0.637 of the ISBI winner) and with an area under the receiver operating curve of 0.85.
This work illustrates the potential for improving skin cancer classification with enhanced training procedures for CNNs, while avoiding the use of costly equipment or proprietary image data.
Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. ...The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine.
Several recent publications have demonstrated the use of convolutional neural networks to classify images of melanoma at par with board-certified dermatologists. However, the non-availability of a ...public human benchmark restricts the comparability of the performance of these algorithms and thereby the technical progress in this field.
An electronic questionnaire was sent to dermatologists at 12 German university hospitals. Each questionnaire comprised 100 dermoscopic and 100 clinical images (80 nevi images and 20 biopsy-verified melanoma images, each), all open-source. The questionnaire recorded factors such as the years of experience in dermatology, performed skin checks, age, sex and the rank within the university hospital or the status as resident physician. For each image, the dermatologists were asked to provide a management decision (treat/biopsy lesion or reassure the patient). Main outcome measures were sensitivity, specificity and the receiver operating characteristics (ROC).
Total 157 dermatologists assessed all 100 dermoscopic images with an overall sensitivity of 74.1%, specificity of 60.0% and an ROC of 0.67 (range = 0.538–0.769); 145 dermatologists assessed all 100 clinical images with an overall sensitivity of 89.4%, specificity of 64.4% and an ROC of 0.769 (range = 0.613–0.9). Results between test-sets were significantly different (P < 0.05) confirming the need for a standardised benchmark.
We present the first public melanoma classification benchmark for both non-dermoscopic and dermoscopic images for comparing artificial intelligence algorithms with diagnostic performance of 145 or 157 dermatologists. Melanoma Classification Benchmark should be considered as a reference standard for white-skinned Western populations in the field of binary algorithmic melanoma classification.
•This paper provides the first open access melanoma classification benchmark for both non-dermoscopic and dermoscopic images.•Algorithms can now be easily compared to the performance of dermatologists in terms of sensitivity, specificity and ROC.•The melanoma benchmark allows comparability between algorithms of different publications and provides a new reference standard.
Over the past decade, the development of molecular high-throughput methods (omics) increased rapidly and provided new insights for cancer research. In parallel, deep learning approaches revealed the ...enormous potential for medical image analysis, especially in digital pathology. Combining image and omics data with deep learning tools may enable the discovery of new cancer biomarkers and a more precise prediction of patient prognosis. This systematic review addresses different multimodal fusion methods of convolutional neural network-based image analyses with omics data, focussing on the impact of data combination on the classification performance.
PubMed was screened for peer-reviewed articles published in English between January 2015 and June 2021 by two independent researchers. Search terms related to deep learning, digital pathology, omics, and multimodal fusion were combined.
We identified a total of 11 studies meeting the inclusion criteria, namely studies that used convolutional neural networks for haematoxylin and eosin image analysis of patients with cancer in combination with integrated omics data. Publications were categorised according to their endpoints: 7 studies focused on survival analysis and 4 studies on prediction of cancer subtypes, malignancy or microsatellite instability with spatial analysis.
Image-based classifiers already show high performances in prognostic and predictive cancer diagnostics. The integration of omics data led to improved performance in all studies described here. However, these are very early studies that still require external validation to demonstrate their generalisability and robustness. Further and more comprehensive studies with larger sample sizes are needed to evaluate performance and determine clinical benefits.
•Fusion of image and genomic data with deep learning improves performance.•Several studies showed a benefit for cancer research.•The studies are at a very early stage and require external validation.•Further studies are needed to demonstrate clinical benefits.
Melanoma is the most dangerous type of skin cancer but is curable if detected early. Recent publications demonstrated that artificial intelligence is capable in classifying images of benign nevi and ...melanoma with dermatologist-level precision. However, a statistically significant improvement compared with dermatologist classification has not been reported to date.
For this comparative study, 4204 biopsy-proven images of melanoma and nevi (1:1) were used for the training of a convolutional neural network (CNN). New techniques of deep learning were integrated. For the experiment, an additional 804 biopsy-proven dermoscopic images of melanoma and nevi (1:1) were randomly presented to dermatologists of nine German university hospitals, who evaluated the quality of each image and stated their recommended treatment (19,296 recommendations in total). Three McNemar's tests comparing the results of the CNN's test runs in terms of sensitivity, specificity and overall correctness were predefined as the main outcomes.
The respective sensitivity and specificity of lesion classification by the dermatologists were 67.2% (95% confidence interval CI: 62.6%–71.7%) and 62.2% (95% CI: 57.6%–66.9%). In comparison, the trained CNN achieved a higher sensitivity of 82.3% (95% CI: 78.3%–85.7%) and a higher specificity of 77.9% (95% CI: 73.8%–81.8%). The three McNemar's tests in 2 × 2 tables all reached a significance level of p < 0.001. This significance level was sustained for both subgroups.
For the first time, automated dermoscopic melanoma image classification was shown to be significantly superior to both junior and board-certified dermatologists (p < 0.001).
•Recent publications demonstrated that deep learning is capable to classify images of benign nevi and melanoma with dermatologist-level precision.•A systematic outperformance of dermatologists was not demonstrated to date.•This study shows the first systematic (p < 0.001) outperformance of board-certified dermatologists in dermoscopic melanoma image classification.
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