AI-Enabled Lung Cancer Prognosis

Lung cancer is the primary cause of cancer-related mortality, claiming approximately 1.79 million lives globally in 2020, with an estimated 2.21 million new cases diagnosed within the same period. Among these, Non-Small Cell Lung Cancer (NSCLC) is the predominant subtype, characterized by a notably bleak prognosis and low overall survival rate of approximately 25% over five years across all disease stages. However, survival outcomes vary considerably based on the stage at diagnosis and the therapeutic interventions administered. Recent advancements in artificial intelligence (AI) have revolutionized the landscape of lung cancer prognosis. AI-driven methodologies, including machine learning and deep learning algorithms, have shown promise in enhancing survival prediction accuracy by efficiently analyzing complex multi-omics data and integrating diverse clinical variables. By leveraging AI techniques, clinicians can harness comprehensive prognostic insights to tailor personalized treatment strategies, ultimately improving patient outcomes in NSCLC. Overviewing AI-driven data processing can significantly help bolster the understanding and provide better directions for using such systems.Comment: This is the author's version of a book chapter entitled: "Cancer Research: An Interdisciplinary Approach", Springe

Combining Molecular, Imaging, and Clinical Data Analysis for Predicting Cancer Prognosis

Cancer is one of the most detrimental diseases globally. Accordingly, the prognosis prediction of cancer patients has become a field of interest. In this review, we have gathered 43 stateof- the-art scientific papers published in the last 6 years that built cancer prognosis predictive models using multimodal data. We have defined the multimodality of data as four main types: clinical, anatomopathological, molecular, and medical imaging; and we have expanded on the information that each modality provides. The 43 studies were divided into three categories based on the modelling approach taken, and their characteristics were further discussed together with current issues and future trends. Research in this area has evolved from survival analysis through statistical modelling using mainly clinical and anatomopathological data to the prediction of cancer prognosis through a multi-faceted data-driven approach by the integration of complex, multimodal, and high-dimensional data containing multi-omics and medical imaging information and by applying Machine Learning and, more recently, Deep Learning techniques. This review concludes that cancer prognosis predictive multimodal models are capable of better stratifying patients, which can improve clinical management and contribute to the implementation of personalised medicine as well as provide new and valuable knowledge on cancer biology and its progression

Radiological evaluation of biomarkers for renal cell carcinoma

Role of MRI DWI sequences in the evaluation of early response to neo- angiogenesis inhibitors in metastatic renal cell carcinoma Purpose: Angiogenesis inhibitors have a potential role in treating metastatic renal cell carcinoma, but it is still not clear why some patients don't respond. Our objective was to look for DWI parameters able to identify patients with metastatic renal cell carcinoma who would not benefit from target therapy. RECIST1.1 was considered as Reference Standard. Methods & Materials: We prospectively enrolled 43 patients candidate to start angiogenesis inhibitors with at least one target lesion and who underwent 1,5T MRI examination with multiple bvalues DWI sequences (0,40,200,300,600): one week before (t0), 2 weeks after (t2) and 8 weeks (t8) after treatment beginning. ADC value was calculated drawing ROIs on 3 different planes. 33 patients with 38 lesions had suitable data for comparative evaluation. Results: At T8 follow-up 9 patients had partial response (PR), 20 table disease (SD), 4 progression disease (PD); average progression free survival was 272 days. PD group, as compared to DC or to PR showed significantly lower ADC values at b40 at t0 (p<0.05): we can assess that more vascularised lesions are more responsive to treatment. PD group have significantly lower ADC values then both other groups, at t0, t2 and t8, for all b-values (p<0.05). PFS and OS correlates well with ADC, in particular OS with ADC b40 at t0 (r=0,69). Coclusions: Results show that PD group has significantly lower ADC values than PR or DC everytime (t0, t2, t8) At t0 there is a better correlation between PFS or OS & ADC than PFS & dimensional criteria. ADC at t0 may help selecting patients with promising good response to angiogenesis inhibitors. Moreover at t0 and at t2 ADC has the potential to select patients who wouldn't benefit from angiogenesis inhibitors Nowadays, in the era of target therapy, it is crucial to select patients potentially responders. We have to look at cost/benefit ratio and at increasing costs of treatment options. DWI has the potential role to identify patients whose's tumor wouldn't benefit from target therapy, adding a value (ADC) to other imaging (e.g. DCE-MRI, texture imaging) and clinical parameters (e.g. miRNA) in a hypothetic multiparametric analysis.CT Texture Analysis in Clear Cell Renal Cell Carcinoma: a Radiogenomics Prospective Purpose: The aim of this study was to investigate whether quantitative parameters obtained from CT Texture Analysis (CTTA) correlate with expression of miRNA in clear cell Renal Cell Carcinoma (ccRCC). Methods and Materials: In a retrospective single centre study, multiphasic CT examination (with arterial, portal, equilibrium and urographic phases) was performed on 20 patients with clear cell renal carcinomas (14 men and 6 women; mean age 65 years ± 13). Measures of heterogeneity were obtained in post-processing by placing a ROI on the entire tumour and CTTA parameters such as entropy, kurtosis, skewness, mean, mean of positive pixels, and SD of pixel distribution histogram were measured using multiple filter settings. Quantitative data were correlated with the expression of miRNAs obtained from the same cohort of patients: 8 fresh frozen samples and 12 formalin-fixed paraffin-embedded samples (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both evaluations (miRNAs and CTTA) were performed on tumour tissues as well as on normal cortico-medullar tissues. Analysis of Variance with linear multiple regression model methods were obtained with SPSS statistic software. For all comparisons, statistical significance was assumed p<0.05 Results: We evidenced that CTTA has robust parameters (e.g. entropy, mean, sd) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression (R2 =0,25) was evidenced in tumour tissues as compared to normal tissues (R2 =0,15). Interestingly, excluding four patients with extreme over-expression of miR-21-5p, excellent relation between entropy and miR21-5p levels was found specifically in tumour samples (R2= 0,64; p<0.05). Conclusion: Entropy and miRNA-21-5p show promising correlation in ccRCC; in addiction CTTA features, in particular mean and entropy show a statistically significant increase in ccRCC as compared with normal renal parenchyma

EPMA position paper in cancer:current overview and future perspectives

At present, a radical shift in cancer treatment is occurring in terms of predictive, preventive, and personalized medicine (PPPM). Individual patients will participate in more aspects of their healthcare. During the development of PPPM, many rapid, specific, and sensitive new methods for earlier detection of cancer will result in more efficient management of the patient and hence a better quality of life. Coordination of the various activities among different healthcare professionals in primary, secondary, and tertiary care requires well-defined competencies, implementation of training and educational programs, sharing of data, and harmonized guidelines. In this position paper, the current knowledge to understand cancer predisposition and risk factors, the cellular biology of cancer, predictive markers and treatment outcome, the improvement in technologies in screening and diagnosis, and provision of better drug development solutions are discussed in the context of a better implementation of personalized medicine. Recognition of the major risk factors for cancer initiation is the key for preventive strategies (EPMA J. 4(1):6, 2013). Of interest, cancer predisposing syndromes in particular the monogenic subtypes that lead to cancer progression are well defined and one should focus on implementation strategies to identify individuals at risk to allow preventive measures and early screening/diagnosis. Implementation of such measures is disturbed by improper use of the data, with breach of data protection as one of the risks to be heavily controlled. Population screening requires in depth cost-benefit analysis to justify healthcare costs, and the parameters screened should provide information that allow an actionable and deliverable solution, for better healthcare provision

Application of digital pathology-based advanced analytics of tumour microenvironment organisation to predict prognosis and therapeutic response.

In recent years, the application of advanced analytics, especially artificial intelligence (AI), to digital H&E images, and other histological image types, has begun to radically change how histological images are used in the clinic. Alongside the recognition that the tumour microenvironment (TME) has a profound impact on tumour phenotype, the technical development of highly multiplexed immunofluorescence platforms has enhanced the biological complexity that can be captured in the TME with high precision. AI has an increasingly powerful role in the recognition and quantitation of image features and the association of such features with clinically important outcomes, as occurs in distinct stages in conventional machine learning. Deep-learning algorithms are able to elucidate TME patterns inherent in the input data with minimum levels of human intelligence and, hence, have the potential to achieve clinically relevant predictions and discovery of important TME features. Furthermore, the diverse repertoire of deep-learning algorithms able to interrogate TME patterns extends beyond convolutional neural networks to include attention-based models, graph neural networks, and multimodal models. To date, AI models have largely been evaluated retrospectively, outside the well-established rigour of prospective clinical trials, in part because traditional clinical trial methodology may not always be suitable for the assessment of AI technology. However, to enable digital pathology-based advanced analytics to meaningfully impact clinical care, specific measures of 'added benefit' to the current standard of care and validation in a prospective setting are important. This will need to be accompanied by adequate measures of explainability and interpretability. Despite such challenges, the combination of expanding datasets, increased computational power, and the possibility of integration of pre-clinical experimental insights into model development means there is exciting potential for the future progress of these AI applications. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Multimodal Data Fusion and Quantitative Analysis for Medical Applications

Medical big data is not only enormous in its size, but also heterogeneous and complex in its data structure, which makes conventional systems or algorithms difficult to process. These heterogeneous medical data include imaging data (e.g., Positron Emission Tomography (PET), Computerized Tomography (CT), Magnetic Resonance Imaging (MRI)), and non-imaging data (e.g., laboratory biomarkers, electronic medical records, and hand-written doctor notes). Multimodal data fusion is an emerging vital field to address this urgent challenge, aiming to process and analyze the complex, diverse and heterogeneous multimodal data. The fusion algorithms bring great potential in medical data analysis, by 1) taking advantage of complementary information from different sources (such as functional-structural complementarity of PET/CT images) and 2) exploiting consensus information that reflects the intrinsic essence (such as the genetic essence underlying medical imaging and clinical symptoms). Thus, multimodal data fusion benefits a wide range of quantitative medical applications, including personalized patient care, more optimal medical operation plan, and preventive public health. Though there has been extensive research on computational approaches for multimodal fusion, there are three major challenges of multimodal data fusion in quantitative medical applications, which are summarized as feature-level fusion, information-level fusion and knowledge-level fusion: • Feature-level fusion. The first challenge is to mine multimodal biomarkers from high-dimensional small-sample multimodal medical datasets, which hinders the effective discovery of informative multimodal biomarkers. Specifically, efficient dimension reduction algorithms are required to alleviate "curse of dimensionality" problem and address the criteria for discovering interpretable, relevant, non-redundant and generalizable multimodal biomarkers. • Information-level fusion. The second challenge is to exploit and interpret inter-modal and intra-modal information for precise clinical decisions. Although radiomics and multi-branch deep learning have been used for implicit information fusion guided with supervision of the labels, there is a lack of methods to explicitly explore inter-modal relationships in medical applications. Unsupervised multimodal learning is able to mine inter-modal relationship as well as reduce the usage of labor-intensive data and explore potential undiscovered biomarkers; however, mining discriminative information without label supervision is an upcoming challenge. Furthermore, the interpretation of complex non-linear cross-modal associations, especially in deep multimodal learning, is another critical challenge in information-level fusion, which hinders the exploration of multimodal interaction in disease mechanism. • Knowledge-level fusion. The third challenge is quantitative knowledge distillation from multi-focus regions on medical imaging. Although characterizing imaging features from single lesions using either feature engineering or deep learning methods have been investigated in recent years, both methods neglect the importance of inter-region spatial relationships. Thus, a topological profiling tool for multi-focus regions is in high demand, which is yet missing in current feature engineering and deep learning methods. Furthermore, incorporating domain knowledge with distilled knowledge from multi-focus regions is another challenge in knowledge-level fusion. To address the three challenges in multimodal data fusion, this thesis provides a multi-level fusion framework for multimodal biomarker mining, multimodal deep learning, and knowledge distillation from multi-focus regions. Specifically, our major contributions in this thesis include: • To address the challenges in feature-level fusion, we propose an Integrative Multimodal Biomarker Mining framework to select interpretable, relevant, non-redundant and generalizable multimodal biomarkers from high-dimensional small-sample imaging and non-imaging data for diagnostic and prognostic applications. The feature selection criteria including representativeness, robustness, discriminability, and non-redundancy are exploited by consensus clustering, Wilcoxon filter, sequential forward selection, and correlation analysis, respectively. SHapley Additive exPlanations (SHAP) method and nomogram are employed to further enhance feature interpretability in machine learning models. • To address the challenges in information-level fusion, we propose an Interpretable Deep Correlational Fusion framework, based on canonical correlation analysis (CCA) for 1) cohesive multimodal fusion of medical imaging and non-imaging data, and 2) interpretation of complex non-linear cross-modal associations. Specifically, two novel loss functions are proposed to optimize the discovery of informative multimodal representations in both supervised and unsupervised deep learning, by jointly learning inter-modal consensus and intra-modal discriminative information. An interpretation module is proposed to decipher the complex non-linear cross-modal association by leveraging interpretation methods in both deep learning and multimodal consensus learning. • To address the challenges in knowledge-level fusion, we proposed a Dynamic Topological Analysis framework, based on persistent homology, for knowledge distillation from inter-connected multi-focus regions in medical imaging and incorporation of domain knowledge. Different from conventional feature engineering and deep learning, our DTA framework is able to explicitly quantify inter-region topological relationships, including global-level geometric structure and community-level clusters. K-simplex Community Graph is proposed to construct the dynamic community graph for representing community-level multi-scale graph structure. The constructed dynamic graph is subsequently tracked with a novel Decomposed Persistence algorithm. Domain knowledge is incorporated into the Adaptive Community Profile, summarizing the tracked multi-scale community topology with additional customizable clinically important factors

The State of Applying Artificial Intelligence to Tissue Imaging for Cancer Research and Early Detection

Artificial intelligence represents a new frontier in human medicine that could save more lives and reduce the costs, thereby increasing accessibility. As a consequence, the rate of advancement of AI in cancer medical imaging and more particularly tissue pathology has exploded, opening it to ethical and technical questions that could impede its adoption into existing systems. In order to chart the path of AI in its application to cancer tissue imaging, we review current work and identify how it can improve cancer pathology diagnostics and research. In this review, we identify 5 core tasks that models are developed for, including regression, classification, segmentation, generation, and compression tasks. We address the benefits and challenges that such methods face, and how they can be adapted for use in cancer prevention and treatment. The studies looked at in this paper represent the beginning of this field and future experiments will build on the foundations that we highlight