Predict Epidermal Growth Factor Receptor Mutation Research Articles

Habitat radiomics and deep learning fusion nomogram to predict EGFR mutation status in stage I non-small cell lung cancer: a multicenter study

Develop a radiomics nomogram that integrates deep learning, radiomics, and clinical variables to predict epidermal growth factor receptor (EGFR) mutation status in patients with stage I non-small cell lung cancer (NSCLC). We retrospectively included 438 patients who underwent curative surgery and completed driver-gene mutation tests for stage I NSCLC from four academic medical centers. Predictive models were established by extracting and analyzing radiomic features in intratumoral, peritumoral, and habitat regions of CT images to identify EGFR mutation status in stage I NSCLC. Additionally, three deep learning models based on the intratumoral region were constructed. A nomogram was developed by integrating representative radiomic signatures, deep learning, and clinical features. Model performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve. The established habitat radiomics features demonstrated encouraging performance in discriminating between EGFR mutant and wild-type, with predictive ability superior to other single models (AUC 0.886, 0.812, and 0.790 for the training, validation, and external test sets, respectively). The radiomics-based nomogram exhibited excellent performance, achieving the highest AUC values of 0.917, 0.837, and 0.809 in the training, validation, and external test sets, respectively. Decision curve analysis (DCA) indicated that the nomogram provided a higher net benefit than other radiomics models, offering valuable information for treatment.

Prediction of Epidermal Growth Factor Receptor Mutation Subtypes in Non–Small Cell Lung Cancer From Hematoxylin and Eosin–Stained Slides Using Deep Learning

Accurate assessment of epidermal growth factor receptor (EGFR) mutation status and subtype is critical for the treatment of non–small cell lung cancer patients. Conventional molecular testing methods for detecting EGFR mutations have limitations. In this study, an artificial intelligence–powered deep learning framework was developed for the weakly supervised prediction of EGFR mutations in non–small cell lung cancer from hematoxylin and eosin–stained histopathology whole-slide images. The study cohort was partitioned into training and validation subsets. Foreground regions containing tumor tissue were extracted from whole-slide images. A convolutional neural network employing a contrastive learning paradigm was implemented to extract patch-level morphologic features. These features were aggregated using a vision transformer-based model to predict EGFR mutation status and classify patient cases. The established prediction model was validated on unseen data sets. In internal validation with a cohort from the University of Science and Technology of China (n = 172), the model achieved patient-level areas under the receiver-operating characteristic curve (AUCs) of 0.927 and 0.907, sensitivities of 81.6% and 83.3%, and specificities of 93.0% and 92.3%, for surgical resection and biopsy specimens, respectively, in EGFR mutation subtype prediction. External validation with cohorts from the Second Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of Wannan Medical College (n = 193) yielded patient-level AUCs of 0.849 and 0.867, sensitivities of 79.2% and 80.7%, and specificities of 91.7% and 90.7% for surgical and biopsy specimens, respectively. Further validation with the Cancer Genome Atlas data set (n = 81) showed an AUC of 0.861, a sensitivity of 84.6%, and a specificity of 90.5%. Deep learning solutions demonstrate potential advantages for automated, noninvasive, fast, cost-effective, and accurate inference of EGFR alterations from histomorphology. Integration of such artificial intelligence frameworks into routine digital pathology workflows could augment existing molecular testing pipelines.

GMILT: A Novel Transformer Network That Can Noninvasively Predict EGFR Mutation Status.

Noninvasively and accurately predicting the epidermal growth factor receptor (EGFR) mutation status is a clinically vital problem. Moreover, further identifying the most suspicious area related to the EGFR mutation status can guide the biopsy to avoid false negatives. Deep learning methods based on computed tomography (CT) images may improve the noninvasive prediction of EGFR mutation status and potentially help clinicians guide biopsies by visual methods. Inspired by the potential inherent links between EGFR mutation status and invasiveness information, we hypothesized that the predictive performance of a deep learning network can be improved through extra utilization of the invasiveness information. Here, we created a novel explainable transformer network for EGFR classification named gated multiple instance learning transformer (GMILT) by integrating multi-instance learning and discriminative weakly supervised feature learning. Pathological invasiveness information was first introduced into the multitask model as embeddings. GMILT was trained and validated on a total of 512 patients with adenocarcinoma and tested on three datasets (the internal test dataset, the external test dataset, and The Cancer Imaging Archive (TCIA) public dataset). The performance (area under the curve (AUC) =0.772 on the internal test dataset) of GMILT exceeded that of previously published methods and radiomics-based methods (i.e., random forest and support vector machine) and attained a preferable generalization ability (AUC =0.856 in the TCIA test dataset and AUC =0.756 in the external dataset). A diameter-based subgroup analysis further verified the efficiency of our model (most of the AUCs exceeded 0.772) to noninvasively predict EGFR mutation status from computed tomography (CT) images. In addition, because our method also identified the "core area" of the most suspicious area related to the EGFR mutation status, it has the potential ability to guide biopsies.

Prognostic and predictive value of interstitial lung abnormalities and EGFR mutation status in patients with non-small cell lung cancer

BackgroundTo determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC).MethodsWe reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors.ResultsEGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861–0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042–0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type.ConclusionNon-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC.

The value of dynamic FDG PET/CT in the differential diagnosis of lung cancer and predicting EGFR mutations

Objectives18F-fluorodeoxyglucose (FDG) PET/CT has been widely used for the differential diagnosis of cancer. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may make it difficult to differentiate between benign and malignant lesions. It is crucial to find reliable quantitative metabolic parameters to further support the diagnosis. This study aims to evaluate the value of the quantitative metabolic parameters derived from dynamic FDG PET/CT in the differential diagnosis of lung cancer and predicting epidermal growth factor receptor (EGFR) mutation status.MethodsWe included 147 patients with lung lesions to perform FDG PET/CT dynamic plus static imaging with informed consent. Based on the results of the postoperative pathology, the patients were divided into benign/malignant groups, adenocarcinoma (AC)/squamous carcinoma (SCC) groups, and EGFR-positive (EGFR+)/EGFR-negative (EGFR-) groups. Quantitative parameters including K1, k2, k3, and Ki of each lesion were obtained by applying the irreversible two-tissue compartmental modeling using an in-house Matlab software. The SUV analysis was performed based on conventional static scan data. Differences in each metabolic parameter among the group were analyzed. Wilcoxon rank-sum test, independent-samples T-test, and receiver-operating characteristic (ROC) analysis were performed to compare the diagnostic effects among the differentiated groups. P < 0.05 were considered statistically significant for all statistical tests.ResultsIn the malignant group (N = 124), the SUVmax, k2, k3, and Ki were higher than the benign group (N = 23), and all had-better performance in the differential diagnosis (P < 0.05, respectively). In the AC group (N = 88), the SUVmax, k3, and Ki were lower than in the SCC group, and such differences were statistically significant (P < 0.05, respectively). For ROC analysis, Ki with cut-off value of 0.0250 ml/g/min has better diagnostic specificity than SUVmax (AUC = 0.999 vs. 0.70). In AC group, 48 patients further underwent EGFR testing. In the EGFR (+) group (N = 31), the average Ki (0.0279 ± 0.0153 ml/g/min) was lower than EGFR (-) group (N = 17, 0.0405 ± 0.0199 ml/g/min), and the difference was significant (P < 0.05). However, SUVmax and k3 did not show such a difference between EGFR (+) and EGFR (-) groups (P>0.05, respectively). For ROC analysis, the Ki had a cut-off value of 0.0350 ml/g/min when predicting EGFR status, with a sensitivity of 0.710, a specificity of 0.588, and an AUC of 0.674 [0.523–0.802].ConclusionAlthough both techniques were specific, Ki had a greater specificity than SUVmax when the cut-off value was set at 0.0250 ml/g/min for the differential diagnosis of lung cancer. At a cut-off value of 0.0350 ml/g/min, there was a 0.710 sensitivity for EGFR status prediction. If EGFR testing is not available for a patient, dynamic imaging could be a valuable non-invasive screening method.

Predicting epidermal growth factor receptor mutations in non-small cell lung cancer through dual-layer spectral CT: a prospective study

ObjectiveTo determine whether quantitative parameters of detector-derived dual-layer spectral computed tomography (DLCT) can reliably identify epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC).MethodsPatients with NSCLC who underwent arterial phase (AP) and venous phase (VP) DLCT between December 2021 and November 2022 were subdivided into the mutated and wild-type EGFR groups following EGFR mutation testing. Their baseline clinical data, conventional CT images, and spectral images were obtained. Iodine concentration (IC), iodine no water (INW), effective atomic number (Zeff), virtual monoenergetic images, the slope of the spectral attenuation curve (λHU), enhancement degree (ED), arterial enhancement fraction (AEF), and normalized AEF (NAEF) were measured for each lesion.ResultsNinety-two patients (median age, 61 years, interquartile range [51, 67]; 33 men) were evaluated. The univariate analysis indicated that IC, normalized IC (NIC), INW and ED for the AP and VP, as well as Zeff and λHU for the VP were significantly associated with EGFR mutation status (all p < 0.05). INW(VP) showed the best diagnostic performance (AUC, 0.892 [95% confidence interval {CI}: 0.823, 0.960]). However, neither AEF (p = 0.156) nor NAEF (p = 0.567) showed significant differences between the two groups. The multivariate analysis showed that INW(AP) and NIC(VP) were significant predictors of EGFR mutation status, with the latter showing better performance (p = 0.029; AUC, 0.897 [95% CI: 0.816, 0.951] vs. 0.774 [95% CI: 0.675, 0.855]).ConclusionQuantitative parameters of DLCT can help predict EGFR mutation status in patients with NSCLC.Critical relevance statementQuantitative parameters of DLCT, especially NIC(VP), can help predict EGFR mutation status in patients with NSCLC, facilitating appropriate and individualized treatment for them.Key PointsDetermining EGFR mutation status in patients with NSCLC before starting therapy is essential.Quantitative parameters of DLCT can predict EGFR mutation status in NSCLC patients.NIC in venous phase is an important parameter to guide individualized treatment selection for NSCLC patients.Graphical

Value of multi-center 18F-FDG PET/CT radiomics in predicting EGFR mutation status in lung adenocarcinoma.

Accurate, noninvasive, and reliable assessment of epidermal growth factor receptor (EGFR) mutation status and EGFR molecular subtypes is essential for treatment plan selection and individualized therapy in lung adenocarcinoma (LUAD). Radiomics models based on 18F-FDG PET/CT have great potential in identifying EGFR mutation status and EGFR subtypes in patients with LUAD. The validation of multi-center data, model visualization, and interpretation are significantly important for the management, application and trust of machine learning predictive models. However, few EGFR-related research involved model visualization and interpretation, and multi-center trial. To develop explainable optimal predictive models based on handcrafted radiomics features (HRFs) extracted from multi-center 18F-FDG PET/CT to predict EGFR mutation status and molecular subtypes in LUAD. Baseline 18F-FDG PET/CT images of 383 LUAD patients from three hospitals and one public data set were collected. Further, 1808 HRFs were extracted from the primary tumor regions using Pyradiomics. Predictive models were built based on cross-combination of seven feature selection methods and seven machine learning algorithms. Yellowbrick and explainable artificial intelligence technology were used for model visualization and interpretation. Receiver operating characteristic curve, classification report and confusion matrix were used for model performance evaluation. Clinical applicability of the optimal models was assessed by decision curve analysis. STACK feature selection method combined with light gradient boosting machine (LGBM) reached optimal performance in identifying EGFR mutation status ([area under the curve] AUC=0.81 in the internal test cohort; AUC=0.62 in the external test cohort). Random forest feature selection method combined with LGBM reached optimal performance in predicting EGFR mutation molecular subtypes (AUC=0.89 in the internal test cohort; AUC=0.61 in the external test cohort). Explainable machine learning models combined with radiomics features extracted from multi-center/scanner 18F-FDG PET/CT have certain potential to identify EGFR mutation status and subtypes in LUAD, which might be helpful to the treatment of LUAD.

Deep learning–radiomics integrated noninvasive detection of epidermal growth factor receptor mutations in non-small cell lung cancer patients

This study focused on a novel strategy that combines deep learning and radiomics to predict epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT). A total of 1280 patients with NSCLC who underwent contrast-enhanced CT scans and EGFR mutation testing before treatment were selected for the final study. Regions of interest were segmented from the CT images to extract radiomics features and obtain tumor images. These tumor images were input into a convolutional neural network model to extract 512 image features, which were combined with radiographic features and clinical data to predict the EGFR mutation. The generalization performance of the model was evaluated using external institutional data. The internal and external datasets contained 324 and 130 EGFR mutants, respectively. Sex, height, weight, smoking history, and clinical stage were significantly different between the EGFR-mutant patient groups. The EGFR mutations were predicted by combining the radiomics and clinical features, and an external validation dataset yielded an area under the curve (AUC) value of 0.7038. The model utilized 1280 tumor images, radiomics features, and clinical characteristics as input data and exhibited an AUC of approximately 0.81 and 0.78 during the primary cohort and external validation, respectively. These results indicate the feasibility of integrating radiomics analysis with deep learning for predicting EGFR mutations. CT-image-based genetic testing is a simple EGFR mutation prediction method, which can improve the prognosis of NSCLC patients and help establish personalized treatment strategies.

A deep learning model integrating multisequence MRI to predict EGFR mutation subtype in brain metastases from non-small cell lung cancer.

To establish a predictive model based on multisequence magnetic resonance imaging (MRI) using deep learning to identify wild-type (WT) epidermal growth factor receptor (EGFR), EGFR exon 19 deletion (19Del), and EGFR exon 21-point mutation (21L858R) simultaneously. A total of 399 patients with proven brain metastases of non-small cell lung cancer (NSCLC) were retrospectively enrolled and divided into training (n = 306) and testing (n = 93) cohorts separately based on two timepoints. All patients underwent 3.0-T brain MRI including T2-weighted, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted imaging, and contrast-enhanced T1-weighted sequences. Radiomics features were extracted from each lesion based on four sequences. An algorithm combining radiomics approach with graph convolutional networks architecture (Radio-GCN) was designed for the prediction of EGFR mutation status and subtype. The area under the curve (AUC) at receiver operating characteristic analysis was used to evaluate the predication capabilities of each model. We extracted 1,290 radiomics features from each MRI sequence. The AUCs of the Radio-GCN model for identifying EGFR 19Del, 21L858R, and WT for the lesion-wise analysis were 0.996 ± 0.004, 0.971 ± 0.013, and 1.000 ± 0.000 on the independent testing cohort separately. It also yielded AUCs of 1.000 ± 0.000, 0.991 ± 0.009, and 1.000 ± 0.000for predicting EGFR mutations respectively for the patient-wise analysis. The κ coefficients were 0.735 and 0.812, respectively. The constructed Radio-GCN model is a new potential tool to predict the EGFR mutation status and subtype in NSCLC patients with brain metastases. The study demonstrated that a deep learning approach based on multisequence MRI can help to predict the EGFR mutation status in NSCLC patients with brain metastases, which is beneficial to guide a personalized treatment. • This is the first study to predict the EGFR mutation subtype simultaneously. • The Radio-GCN model holds the potential to be used as a diagnostic tool. • This study provides an imaging surrogate for identifying the EGFR mutation subtype.

Dual-energy CT-based radiomics in predicting EGFR mutation status non-invasively in lung adenocarcinoma

ObjectivesPatients with epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD) can benefit from individualized targeted therapy. This study aims to develop, compare, analyse prediction models based on dual-energy spectral computed tomography (DESCT) and CT-based radiomic features to non-invasively predict EGFR mutation status in LUAD. Materials and methodsPatients with LUAD (n = 175), including 111 patients with and 64 patients without EGFR mutations, were enrolled in the current study. All patients were randomly divided into a training dataset (122 cases) and validation dataset (53 cases) at a ratio of 7:3. After extracting CT-based radiomic, DESCT and clinical features, we built seven prediction models and a nomogram of the best prediction. Receiver operating characteristic (ROC) curves and the mean area under the curve (AUC) values were used for comparisons among the models to obtain the best prediction model for predicting EGFR mutations. ResultsThe best distinguishing ability is the combined model incorporating radiomic, DESCT and clinical features for predicting the EGFR mutation status with an AUC of 0.86 (95 % CI: 0.79–0.92) in the training group and an AUC value of 0.83 (95 % CI: 0.73, 0.96) in the validation group. ConclusionsOur study provides a predictive nomogram non-invasively with a combination of CT-based radiomic, DESCT and clinical features, which can provide image-based biological information for targeted therapy of LUAD with EGFR mutations.

End-to-end Prediction of EGFR Mutation Status with Denseformer.

Accurate genotyping of the epidermal growth factor receptor (EGFR) is critical for the treatment planning of lung adenocarcinoma. Currently, clinical identification of EGFR genotyping highly relies on biopsy and sequence testing which is invasive and complicated. Recent advancements in the integration of computed tomography (CT) imagery with deep learning techniques have yielded a non-invasive and straightforward way for identifying EGFR profiles. However, there are still many limitations for further exploration: 1) most of these methods still require physicians to annotate tumor boundaries, which are time-consuming and prone to subjective errors; 2) most of the existing methods are simply borrowed from computer vision field which does not sufficiently exploit the multi-level features for final prediction. To solve these problems, we propose a Denseformer framework to identify EGFR mutation status in a real end-to-end fashion directly from 3D lung CT images. Specifically, we take the 3D whole-lung CT images as the input of the neural network model without manually labeling the lung nodules. This is inspired by the medical report that the mutational status of EGFR is associated not only with the local tumor nodules but also with the microenvironment surrounded by the whole lung. Besides, we design a novel Denseformer network to fully explore the distinctive information across the different level features. The Denseformer is a novel network architecture that combines the advantages of both convolutional neural network (CNN) and Transformer. Denseformer directly learns from the 3D whole-lung CT images, which preserves the spatial location information in the CT images. To further improve the model performance, we designed a combined Transformer module. This module employs the Transformer Encoder to globally integrate the information of different levels and layers and use them as the basis for the final prediction. The proposed model has been tested on a lung adenocarcinoma dataset collected at the Affiliated Hospital of Zunyi Medical University. Extensive experiments demonstrated the proposed method can effectively extract meaningful features from 3D CT images to make accurate predictions. Compared with other state-of-the-art methods, Denseformer achieves the best performance among current methods using deep learning to predict EGFR mutation status based on a single modality of CT images.

Hybrid deep multi-task learning radiomics approach for predicting EGFR mutation status of non-small cell lung cancer in CT images

Objective. Epidermal growth factor receptor (EGFR) mutation genotyping plays a pivotal role in targeted therapy for non-small cell lung cancer (NSCLC). We aimed to develop a computed tomography (CT) image-based hybrid deep radiomics model to predict EGFR mutation status in NSCLC and investigate the correlations between deep image and quantitative radiomics features. Approach. First, we retrospectively enrolled 818 patients from our centre and 131 patients from The Cancer Imaging Archive database to establish a training cohort (N = 654), an independent internal validation cohort (N = 164) and an external validation cohort (N = 131). Second, to predict EGFR mutation status, we developed three CT image-based models, namely, a multi-task deep neural network (DNN), a radiomics model and a feature fusion model. Third, we proposed a hybrid loss function to train the DNN model. Finally, to evaluate the model performance, we computed the areas under the receiver operating characteristic curves (AUCs) and decision curve analysis curves of the models. Main results. For the two validation cohorts, the feature fusion model achieved AUC values of 0.86 ± 0.03 and 0.80 ± 0.05, which were significantly higher than those of the single-task DNN and radiomics models (all P < 0.05). There was no significant difference between the feature fusion and the multi-task DNN models (P > 0.8). The binary prediction scores showed excellent prognostic value in predicting disease-free survival (P = 0.02) and overall survival (P < 0.005) for validation cohort 2. Significance. The results demonstrate that (1) the feature fusion and multi-task DNN models achieve significantly higher performance than that of the conventional radiomics and single-task DNN models, (2) the feature fusion model can decode the imaging phenotypes representing NSCLC heterogeneity related to both EGFR mutation and patient NSCLC prognosis, and (3) high correlations exist between some deep image and radiomics features.

New research progress on 18F-FDG PET/CT radiomics for EGFR mutation prediction in lung adenocarcinoma: a review

Lung cancer, the most frequently diagnosed cancer worldwide, is the leading cause of cancer-associated deaths. In recent years, significant progress has been achieved in basic and clinical research concerning the epidermal growth factor receptor (EGFR), and the treatment of lung adenocarcinoma has also entered a new era of individualized, targeted therapies. However, the detection of lung adenocarcinoma is usually invasive. 18F-FDG PET/CT can be used as a noninvasive molecular imaging approach, and radiomics can acquire high-throughput data from standard images. These methods play an increasingly prominent role in diagnosing and treating cancers. Herein, we reviewed the progress in applying 18F-FDG PET/CT and radiomics in lung adenocarcinoma clinical research and how these data are analyzed via traditional statistics, machine learning, and deep learning to predict EGFR mutation status, all of which achieved satisfactory results. Traditional statistics extract features effectively, machine learning achieves higher accuracy with complex algorithms, and deep learning obtains significant results through end-to-end methods. Future research should combine these methods to achieve more accurate predictions, providing reliable evidence for the precision treatment of lung adenocarcinoma. At the same time, facing challenges such as data insufficiency and high algorithm complexity, future researchers must continuously explore and optimize to better apply to clinical practice.

Combined radiomics of primary tumour and bone metastasis improve the prediction of EGFR mutation status and response to EGFR-TKI therapy for NSCLC

PurposeTo develop radiomics models of primary tumour and spinal metastases to predict epidermal growth factor receptor (EGFR) mutations and therapeutic response to EGFR-tyrosine kinase inhibitor (TKI) in patients with metastatic non-small-cell lung cancer (NSCLC). MethodsWe enrolled 203 patients with spinal metastases between December 2017 and September 2021, classified as patients with the EGFR mutation or EGFR wild-type. All patients underwent thoracic CT and spinal MRI scans before any treatment. Radiomics analysis was performed to extract features from primary tumour and metastases images and identify predictive features with the least absolute shrinkage and selection operator. Radiomics signatures (RS) were constructed based on primary tumour (RS-Pri), metastases (RS-Met), and in combination (RS-Com) to predict EGFR mutation status and response to EGFR-TKI. Receiver operating characteristic (ROC) curve analysis with 10-fold cross-validation was applied to assess the performance of the models. ResultsTo predict the EGFR mutation status, the RS based on the combination of primary tumour and metastases improved the prediction AUCs compared to those based on the primary tumour or metastasis alone in the training (RS-Com-EGFR: 0.927) and validation (RS-Com-EGFR: 0.812) cohorts. To predict response to EGFR-TKI, the developed RS based on combined primary tumour and metastasis generated the highest AUCs in the training (RS-Com-TKI: 0.880) and validation (RS-Com-TKI: 0.798) cohort. ConclusionsPrimary NSCLC and spinal metastases can provide complementary information to predict the EGFR mutation status and response to EGFR-TKI. The developed models that integrate primary lesions and metastases may be potential imaging markers to guide individual treatment decisions.

Peritumoural MRI radiomics signature of brain metastases can predict epidermal growth factor receptor mutation status in lung adenocarcinoma

To investigate whether magnetic resonance imaging (MRI) radiomics features of brain metastases (BMs) can predict epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma. Between June 2014 and December 2022, 58 histopathologically confirmed lung adenocarcinoma patients (27 with EGFR wild-type, 31 with EGFR mutation) who underwent gadobenate dimeglumine-enhanced brain MRI were recruited retrospectively. A total of 123 metastatic brain lesions were allocated randomly into the training cohort (n=86) and test cohort (n=37) at a ratio of 7:3. Radiomics models based on multi-sequence MRI images in different regions such as volume of interest (VOI)enhancing tumour, VOIwholetumour, VOIperitumour 1mm, VOIperitumour 3mm, and VOIperitumour 5mm were built. The optimal radiomics model was integrated into the clinical or radiological indicators to construct a fusion model through multivariable logistic regression analysis. The optimal radiomics model based on the VOIperitumour 1mm, a combination of nine features selected from the fluid-attenuated inversion recovery (FLAIR) sequence, yielded areas under the curves (AUCs) of >0.75 in the training and test cohorts. The prediction of the fusion model with integration of clinical factors (age) and radiomics score (the optimal radiomics model) was not better than that of the optimal radiomics model alone in the test cohort (AUC: 0.808 and 0.785, respectively, p=0.525). The FLAIR radiomics model based on VOIperitumour 1mm as an effective biomarker helps predict EGFR mutation status in lung adenocarcinoma patients with BMs and then assists clinicians in selecting optimal treatment strategies.

Study on the application of percutaneous closed pleural brushing combined with cell block technique in the diagnosis of malignant pleural effusion.

This study was to investigate the diagnostic value of percutaneous closed pleural brushing (CPBR) followed by cell block technique for malignant pleural effusion (MPE) and the predictive efficacy of pleural fluid carcinoembryonic antigen (CEA) for epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma patients with MPE. All patients underwent closed pleural biopsy (CPB) and CPBR followed by cell block examination. MPE-positive diagnostic rates between the two methods were compared. Univariate and multivariate analyses were performed to determine factors influencing the EGFR mutations. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of pleural fluid CEA for EGFR mutations. The cumulative positive diagnostic rates for MPE after single and twice CPBR followed by cell block examination were 80.5% and 89.0%, higher than CPB (45.7%, 54.3%) (P < 0.001). Univariate analysis showed that EGFR mutation was associated with pleural fluid and serum CEA (P < 0.05). Multivariate analysis showed that pleural fluid CEA was an independent risk factor for predicting EGFR mutation (P < 0.001). The area under the curve (AUC) of pleural fluid CEA for EGFR mutation prediction was 0.774, higher than serum CEA (P = 0.043), but no difference with the combined test (P > 0.05). Compared with CPB, CPBR followed by the cell block technique can significantly increase the positive diagnostic rate of suspected MPE. CEA testing of pleural fluid after CPBR has a high predictive efficacy for EGFR mutation in lung adenocarcinoma patients with MPE, implying pleural fluid extracted for cell block after CPBR may be an ideal specimen for genetic testing.

Computed Tomography-derived intratumoral and peritumoral radiomics in predicting EGFR mutation in lung adenocarcinoma

ObjectiveTo investigate the value of Computed Tomography (CT) radiomics derived from different peritumoral volumes of interest (VOIs) in predicting epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma patients.Materials and methodsA retrospective cohort of 779 patients who had pathologically confirmed lung adenocarcinoma were enrolled. 640 patients were randomly divided into a training set, a validation set, and an internal testing set (3:1:1), and the remaining 139 patients were defined as an external testing set. The intratumoral VOI (VOI_I) was manually delineated on the thin-slice CT images, and seven peritumoral VOIs (VOI_P) were automatically generated with 1, 2, 3, 4, 5, 10, and 15 mm expansion along the VOI_I. 1454 radiomic features were extracted from each VOI. The t-test, the least absolute shrinkage and selection operator (LASSO), and the minimum redundancy maximum relevance (mRMR) algorithm were used for feature selection, followed by the construction of radiomics models (VOI_I model, VOI_P model and combined model). The performance of the models were evaluated by the area under the curve (AUC).Results399 patients were classified as EGFR mutant (EGFR+), while 380 were wild-type (EGFR−). In the training and validation sets, internal and external testing sets, VOI4 (intratumoral and peritumoral 4 mm) model achieved the best predictive performance, with AUCs of 0.877, 0.727, and 0.701, respectively, outperforming the VOI_I model (AUCs of 0.728, 0.698, and 0.653, respectively).ConclusionsRadiomics extracted from peritumoral region can add extra value in predicting EGFR mutation status of lung adenocarcinoma patients, with the optimal peritumoral range of 4 mm.

Predicting EGFR Mutation in Lung Adenocarcinoma: Development and Validation of the EGFR Mutation Predictive Score (EMPS) in Bali, Indonesia.

The examination of epidermal growth factor receptor (EGFR) mutations may not be routinely available to all patients due to the limited availability and the expensive price of the examination, especially in area with limited resources such as in Indonesia. Therefore, we aimed to build a nomogram to predict the EGFR mutation in patients with lung adenocarcinoma by incorporating significant clinical and radiological parameters. We conducted an age-matched case-control study using 160 treatment-naïve patients [80 patients with EGFR-mutated (EGFRmut) and 80 with EGFR-wild-type (EGFRwt)] with pathologically confirmed lung adenocarcinomas with tumor specimens available for genetic analysis taken from 2017 through 2021 in Bali, Indonesia. Radiomics features were extracted from contrast CT images. The cut-off of the tumor diameter was defined using Receiver Operating Characteristic Curve. A conditional logistic regression model was constructed to identify significant risk factors, and a nomogram was developed for predicting the risk of EGFR mutation. A cohort was done to validate the nomogram. Being female, never-smoker, having a smaller tumor diameter (<48.5mm), located in the upper lobe, have bubble-like lucency and air-bronchogram in the chest CT scan were identified as independent risk factors of EGFR mutation at the multivariate logistic regression model. The forming normogram model produced an area under the curve of 0.993 (95 % CI = 0.98-1.00) and 0.91 (95 % CI = 0.84-0.99) in development and validation group, respectively. The calibration curve showed good agreement between predicted and actual probability. At the cut-off point of the normogram score 246 shows a sensitivity of 97.5%, a specificity of 98.8%, a positive predictive value of 99.0%, and a negative predictive value of 96.8%. Our study indicated that the EGFR Mutation Normogram could provide a non-invasive way to predict the risk of EGFR mutation in patients with lung adenocarcinoma in clinical practice. This normogram need to be validated in other area in Indonesia.

A CT-based Deep Learning Radiomics Nomogram for the Prediction of EGFR Mutation Status in Head and Neck Squamous Cell Carcinoma

Accurately assessing epidermal growth factor receptor (EGFR) mutation status in head and neck squamous cell carcinoma (HNSCC) patients is crucial for prognosis and treatment selection. This study aimed to construct and validate a contrast-enhanced computed tomography (CECT)-based deep learning radiomics nomogram (DLRN) to predict EGFR mutation status of HNSCC. A total of 300 HNSCC patients who underwent CECT scans were enrolled in this study. Participants from two hospitals were separated into a training set (n=200, 56 EGFR-negative and 144 EGFR-positive) from one hospital and an external test set from the other hospital (n=100, 37 EGFR-negative and 63 EGFR-positive). The least absolute shrinkage and selection operator method was used to select the key features from CECT-based manually extracted radiomics (MER) features and features automatically extracted using a deep learning model (DL, extracted using a GoogLeNet model). The selected independent clinical factors, MER features, and DL features were then combined to construct a DLRN. The DLRN's performance was evaluated using receiver operating characteristics curves. Five MER and six DL features were finally chosen. The DLRN, which includes "gender" and "necrotic areas," along with the selected features, predicted EGFR mutation status of HNSCC (EGFR-negative vs. positive) well in both the training (area under the curve [AUC], 0.901) and test (AUC, 0.875) sets. A DLRN using CECT was built to predict EGFR mutation in HNSCC. The model showed high predictive ability and may aid in treatment selection and patient prognosis.

High accuracy epidermal growth factor receptor mutation prediction via histopathological deep learning

BackgroundThe detection of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer is critical for tyrosine kinase inhibitor therapy. EGFR detection requires tissue samples, which are difficult to obtain in some patients, costing them the opportunity for further treatment. To realize EGFR mutation prediction without molecular detection, we aimed to build a high-accuracy deep learning model with only haematoxylin and eosin (H&E)-stained slides.MethodsWe collected 326 H&E-stained non-small cell lung cancer slides from Beijing Chest Hospital, China, and used 226 slides (88 with EGFR mutations) for model training. The remaining 100 images (50 with EGFR mutations) were used for testing. We trained a convolutional neural network based on ResNet-50 to classify EGFR mutation status on the slide level.ResultsThe sensitivity and specificity of the model were 76% and 74%, respectively, with an area under the curve of 0.82. When applying the double-threshold approach, 33% of the patients could be predicted by the deep learning model as EGFR positive or negative with a sensitivity and specificity of 100.0% and 87.5%. The remaining 67% of the patients got an uncertain result and will be recommenced to perform further examination. By incorporating adenocarcinoma subtype information, we achieved 100% sensitivity in predicting EGFR mutations in 37.3% of adenocarcinoma patients.ConclusionsOur study demonstrates the potential of a deep learning-based EGFR mutation prediction model for rapid and cost-effective pre-screening. It could serve as a high-accuracy complement to current molecular detection methods and provide treatment opportunities for non-small cell lung cancer patients from whom limited samples are available.