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Publications

Publications by Francisco Carvalho Silva

2021

Ensemble Strategies for EGFR Mutation Status Prediction in Lung Cancer

Authors
Malafaia, M; Pereira, T; Silva, F; Morgado, J; Cunha, A; Oliveira, HP;

Publication
2021 43RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE & BIOLOGY SOCIETY (EMBC)

Abstract
Lung cancer treatments that are accurate and effective are urgently needed. The diagnosis of advanced-stage patients accounts for the majority of the cases, being essential to provide a specialized course of treatment. One emerging course of treatment relies on target therapy through the testing of biomarkers, such as the Epidermal Growth Factor Receptor (EGFR) gene. Such testing can be obtained from invasive methods, namely through biopsy, which may be avoided by applying machine learning techniques to the imaging phenotypes extracted from Computerized Tomography (CT). This study aims to explore the contribution of ensemble methods when applied to the prediction of EGFR mutation status. The obtained results translate in a direct correlation between the semantic predictive model and the outcome of the combined ensemble methods, showing that the utilized features do not have a positive contribution to the predictive developed models.

2021

Stacking Approach for Lung Cancer EGFR Mutation Status Prediction from CT Scans

Authors
Ventura, A; Pereira, T; Silva, F; Freitas, C; Cunha, A; Oliveira, HP;

Publication
IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2021, Houston, TX, USA, December 9-12, 2021

Abstract
Due to the huge mortality rate of lung cancer, there is a strong need for developing solutions that help with the early diagnosis and the definition of the most appropriate treatment. In the particular case of target therapy, effective genotyping of the tumor is fundamental since this treatment uses targeted drugs that can induce death in cancer cells. The biopsy is the traditional method to assess the genotype information but it is extremely invasive and painful. Medical imaging is a valuable alternative to biopsies, considering the potential to extract imaging features correlated with specific genomic alterations. Regarding the limitations of single model approaches for gene mutation status predictions, ensemble strategies might bring valuable benefits by combining the strengths and weaknesses of the aggregated methods. This preliminary work aims to provide further advances in the radiogenomics field by studying the use of ensemble methods to predict the Epidermal Growth Factor Receptor (EGFR) mutation status in lung cancer. The best result obtained for the proposed ensemble approach was an AUC of 0.706 (± 0.122). However, the ensemble did not outperform the single models with AUC values of 0.712 (± 0.119) for Logistic Regression, 0.711 (± 0.119) for Support Vector Machine and 0.712 (± 0.120) for Elastic Net. The high correlation found on the decisions of each single model might be a plausible explanation for this behavior, which caused the ensemble to misclassify the same examples as the single models.

2022

Lung Segmentation in CT Images: A Residual U-Net Approach on a Cross-Cohort Dataset

Authors
Sousa, J; Pereira, T; Silva, F; Silva, MC; Vilares, AT; Cunha, A; Oliveira, HP;

Publication
APPLIED SCIENCES-BASEL

Abstract
Lung cancer is one of the most common causes of cancer-related mortality, and since the majority of cases are diagnosed when the tumor is in an advanced stage, the 5-year survival rate is dismally low. Nevertheless, the chances of survival can increase if the tumor is identified early on, which can be achieved through screening with computed tomography (CT). The clinical evaluation of CT images is a very time-consuming task and computed-aided diagnosis systems can help reduce this burden. The segmentation of the lungs is usually the first step taken in image analysis automatic models of the thorax. However, this task is very challenging since the lungs present high variability in shape and size. Moreover, the co-occurrence of other respiratory comorbidities alongside lung cancer is frequent, and each pathology can present its own scope of CT imaging appearances. This work investigated the development of a deep learning model, whose architecture consists of the combination of two structures, a U-Net and a ResNet34. The proposed model was designed on a cross-cohort dataset and it achieved a mean dice similarity coefficient (DSC) higher than 0.93 for the 4 different cohorts tested. The segmentation masks were qualitatively evaluated by two experienced radiologists to identify the main limitations of the developed model, despite the good overall performance obtained. The performance per pathology was assessed, and the results confirmed a small degradation for consolidation and pneumocystis pneumonia cases, with a DSC of 0.9015 +/- 0.2140 and 0.8750 +/- 0.1290, respectively. This work represents a relevant assessment of the lung segmentation model, taking into consideration the pathological cases that can be found in the clinical routine, since a global assessment could not detail the fragilities of the model.

2022

Towards Machine Learning-Aided Lung Cancer Clinical Routines: Approaches and Open Challenges

Authors
Silva, F; Pereira, T; Neves, I; Morgado, J; Freitas, C; Malafaia, M; Sousa, J; Fonseca, J; Negrao, E; de Lima, BF; da Silva, MC; Madureira, AJ; Ramos, I; Costa, JL; Hespanhol, V; Cunha, A; Oliveira, HP;

Publication
JOURNAL OF PERSONALIZED MEDICINE

Abstract
Advancements in the development of computer-aided decision (CAD) systems for clinical routines provide unquestionable benefits in connecting human medical expertise with machine intelligence, to achieve better quality healthcare. Considering the large number of incidences and mortality numbers associated with lung cancer, there is a need for the most accurate clinical procedures; thus, the possibility of using artificial intelligence (AI) tools for decision support is becoming a closer reality. At any stage of the lung cancer clinical pathway, specific obstacles are identified and motivate the application of innovative AI solutions. This work provides a comprehensive review of the most recent research dedicated toward the development of CAD tools using computed tomography images for lung cancer-related tasks. We discuss the major challenges and provide critical perspectives on future directions. Although we focus on lung cancer in this review, we also provide a more clear definition of the path used to integrate AI in healthcare, emphasizing fundamental research points that are crucial for overcoming current barriers.

2022

Differential Gene Expression Analysis of the Most Relevant Genes for Lung Cancer Prediction and Sub-type Classification

Authors
Ramos, B; Pereira, T; Silva, F; Costa, JL; Oliveira, HP;

Publication
PATTERN RECOGNITION AND IMAGE ANALYSIS (IBPRIA 2022)

Abstract
An early diagnosis of cancer is essential for a good prognosis, and the identification of differentially expressed genes can enable a better personalization of the treatment plan that can target those genes in therapy. This work proposes a pipeline that predicts the presence of lung cancer and the subtype allowing the identification of differentially expressed genes for lung cancer adenocarcinoma and squamous cell carcinoma subtypes. A gradient boosted tree model is used for the classification tasks based on RNA-seq data. The analysis of gene expressions that better differentiate cancerous from normal tissue, and features that distinguish between lung subtypes is the main focus of the present work. Differential expressed genes are analyzed by performing hierarchical clustering in order to identify gene signatures that are commonly regulated and biological signatures associated with a specific subtype. This analysis highlighted patterns of commonly regulated genes already known in the literature as cancer or subtype-specific genes, and others that are not yet documented in the literature.

2022

The Influence of a Coherent Annotation and Synthetic Addition of Lung Nodules for Lung Segmentation in CT Scans

Authors
Sousa, J; Pereira, T; Neves, I; Silva, F; Oliveira, HP;

Publication
SENSORS

Abstract
Lung cancer is a highly prevalent pathology and a leading cause of cancer-related deaths. Most patients are diagnosed when the disease has manifested itself, which usually is a sign of lung cancer in an advanced stage and, as a consequence, the 5-year survival rates are low. To increase the chances of survival, improving the cancer early detection capacity is crucial, for which computed tomography (CT) scans represent a key role. The manual evaluation of the CTs is a time-consuming task and computer-aided diagnosis (CAD) systems can help relieve that burden. The segmentation of the lung is one of the first steps in these systems, yet it is very challenging given the heterogeneity of lung diseases usually present and associated with cancer development. In our previous work, a segmentation model based on a ResNet34 and U-Net combination was developed on a cross-cohort dataset that yielded good segmentation masks for multiple pathological conditions but misclassified some of the lung nodules. The multiple datasets used for the model development were originated from different annotation protocols, which generated inconsistencies for the learning process, and the annotations are usually not adequate for lung cancer studies since they did not comprise lung nodules. In addition, the initial datasets used for training presented a reduced number of nodules, which was showed not to be enough to allow the segmentation model to learn to include them as a lung part. In this work, an objective protocol for the lung mask's segmentation was defined and the previous annotations were carefully reviewed and corrected to create consistent and adequate ground-truth masks for the development of the segmentation model. Data augmentation with domain knowledge was used to create lung nodules in the cases used to train the model. The model developed achieved a Dice similarity coefficient (DSC) above 0.9350 for all test datasets and it showed an ability to cope, not only with a variety of lung patterns, but also with the presence of lung nodules as well. This study shows the importance of using consistent annotations for the supervised learning process, which is a very time-consuming task, but that has great importance to healthcare applications. Due to the lack of massive datasets in the medical field, which consequently brings a lack of wide representativity, data augmentation with domain knowledge could represent a promising help to overcome this limitation for learning models development.

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