Status and Recommendations of Technological and Data-Driven Innovations in Cancer Care: Focus Group Study.

BACKGROUND: The status of the data-driven management of cancer care as well as the challenges, opportunities, and recommendations aimed at accelerating the rate of progress in this field are topics of great interest. Two international workshops, one conducted in June 2019 in Cordoba, Spain, and one in October 2019 in Athens, Greece, were organized by four Horizon 2020 (H2020) European Union (EU)-funded projects: BOUNCE, CATCH ITN, DESIREE, and MyPal. The issues covered included patient engagement, knowledge and data-driven decision support systems, patient journey, rehabilitation, personalized diagnosis, trust, assessment of guidelines, and interoperability of information and communication technology (ICT) platforms. A series of recommendations was provided as the complex landscape of data-driven technical innovation in cancer care was portrayed. OBJECTIVE: This study aims to provide information on the current state of the art of technology and data-driven innovations for the management of cancer care through the work of four EU H2020-funded projects. METHODS: Two international workshops on ICT in the management of cancer care were held, and several topics were identified through discussion among the participants. A focus group was formulated after the second workshop, in which the status of technological and data-driven cancer management as well as the challenges, opportunities, and recommendations in this area were collected and analyzed. RESULTS: Technical and data-driven innovations provide promising tools for the management of cancer care. However, several challenges must be successfully addressed, such as patient engagement, interoperability of ICT-based systems, knowledge management, and trust. This paper analyzes these challenges, which can be opportunities for further research and practical implementation and can provide practical recommendations for future work. CONCLUSIONS: Technology and data-driven innovations are becoming an integral part of cancer care management. In this process, specific challenges need to be addressed, such as increasing trust and engaging the whole stakeholder ecosystem, to fully benefit from these innovations.

A Self-Synthesis Approach to Perceptual Learning for Multisensory Fusion in Robotics.

Biological and technical systems operate in a rich multimodal environment. Due to the diversity of incoming sensory streams a system perceives and the variety of motor capabilities a system exhibits there is no single representation and no singular unambiguous interpretation of such a complex scene. In this work we propose a novel sensory processing architecture, inspired by the distributed macro-architecture of the mammalian cortex. The underlying computation is performed by a network of computational maps, each representing a different sensory quantity. All the different sensory streams enter the system through multiple parallel channels. The system autonomously associates and combines them into a coherent representation, given incoming observations. These processes are adaptive and involve learning. The proposed framework introduces mechanisms for self-creation and learning of the functional relations between the computational maps, encoding sensorimotor streams, directly from the data. Its intrinsic scalability, parallelisation, and automatic adaptation to unforeseen sensory perturbations make our approach a promising candidate for robust multisensory fusion in robotic systems. We demonstrate this by applying our model to a 3D motion estimation on a quadrotor.

Agent-based modeling in cancer biomedicine: applications and tools for calibration and validation.

Computational models are not just appealing because they can simulate and predict the development of biological phenomena across multiple spatial and temporal scales, but also because they can integrate information from well-established in vitro and in vivo models and test new hypotheses in cancer biomedicine. Agent-based models and simulations are especially interesting candidates among computational modeling procedures in cancer research due to the capability to, for instance, recapitulate the dynamics of neoplasia and tumor - host interactions. Yet, the absence of methods to validate the consistency of the results across scales can hinder adoption by turning fine-tuned models into black boxes. This review compiles relevant literature that explores strategies to leverage high-fidelity simulations of multi-scale, or multi-level, cancer models with a focus on verification approached as simulation calibration. We consolidate our review with an outline of modern approaches for agent-based models' validation and provide an ambitious outlook toward rigorous and reliable calibration.

Antifragility as a complex system's response to perturbations, volatility, and time.

Antifragility characterizes the benefit of a dynamical system derived from the variability in environmental perturbations. Antifragility carries a precise definition that quantifies a system's output response to input variability. Systems may respond poorly to perturbations (fragile) or benefit from perturbations (antifragile). In this manuscript, we review a range of applications of antifragility theory in technical systems (e.g., traffic control, robotics) and natural systems (e.g., cancer therapy, antibiotics). While there is a broad overlap in methods used to quantify and apply antifragility across disciplines, there is a need for precisely defining the scales at which antifragility operates. Thus, we provide a brief general introduction to the properties of antifragility in applied systems and review relevant literature for both natural and technical systems' antifragility. We frame this review within three scales common to technical systems: intrinsic (input-output nonlinearity), inherited (extrinsic environmental signals), and interventional (feedback control), with associated counterparts in biological systems: ecological (homogeneous systems), evolutionary (heterogeneous systems), and interventional (control). We use the common noun in designing systems that exhibit antifragile behavior across scales and guide the reader along the spectrum of fragility-adaptiveness-resilience-robustness-antifragility, the principles behind it, and its practical implications.

Data-Driven Discovery of Mathematical and Physical Relations in Oncology Data Using Human-Understandable Machine Learning.

For decades, researchers have used the concepts of rate of change and differential equations to model and forecast neoplastic processes. This expressive mathematical apparatus brought significant insights in oncology by describing the unregulated proliferation and host interactions of cancer cells, as well as their response to treatments. Now, these theories have been given a new life and found new applications. With the advent of routine cancer genome sequencing and the resulting abundance of data, oncology now builds an "arsenal" of new modeling and analysis tools. Models describing the governing physical laws of tumor-host-drug interactions can be now challenged with biological data to make predictions about cancer progression. Our study joins the efforts of the mathematical and computational oncology community by introducing a novel machine learning system for data-driven discovery of mathematical and physical relations in oncology. The system utilizes computational mechanisms such as competition, cooperation, and adaptation in neural networks to simultaneously learn the statistics and the governing relations between multiple clinical data covariates. Targeting an easy adoption in clinical oncology, the solutions of our system reveal human-understandable properties and features hidden in the data. As our experiments demonstrate, our system can describe nonlinear conservation laws in cancer kinetics and growth curves, symmetries in tumor's phenotypic staging transitions, the preoperative spatial tumor distribution, and up to the nonlinear intracellular and extracellular pharmacokinetics of neoadjuvant therapies. The primary goal of our work is to enhance or improve the mechanistic understanding of cancer dynamics by exploiting heterogeneous clinical data. We demonstrate through multiple instantiations that our system is extracting an accurate human-understandable representation of the underlying dynamics of physical interactions central to typical oncology problems. Our results and evaluation demonstrate that, using simple-yet powerful-computational mechanisms, such a machine learning system can support clinical decision-making. To this end, our system is a representative tool of the field of mathematical and computational oncology and offers a bridge between the data, the modeler, the data scientist, and the practicing clinician.

Role of Kinematics Assessment and Multimodal Sensorimotor Training for Motion Deficits in Breast Cancer Chemotherapy-Induced Polyneuropathy: A Perspective on Virtual Reality Avatars.

Chemotherapy-induced polyneuropathy (CIPN), one of the most severe and incapacitating side effects of chemotherapeutic drugs, is a serious concern in breast cancer therapy leading to dose diminution, delay, or cessation. The reversibility of CIPN is of increasing importance since active chemotherapies prolong survival. Clinical assessment tools show that patients experiencing sensorimotor CIPN symptoms not only do they have to cope with loss in autonomy and life quality, but CIPN has become a key restricting factor in treatment. CIPN incidence poses a clinical challenge and has lacked established and efficient therapeutic options up to now. Complementary, non-opioid therapies are sought for both prevention and management of CIPN. In this perspective, we explore the potential that digital interventions have for sensorimotor CIPN rehabilitation in breast cancer patients. Our primary goal is to emphasize the benefits and impact that Virtual Reality (VR) avatars and Machine Learning have in combination in a digital intervention aiming at (1) assessing the complete kinematics of deficits through learning underlying patient sensorimotor parameters, and (2) parameterize a multimodal VR simulation to drive personalized deficit compensation. We support our perspective by evaluating sensorimotor effects of chemotherapy, the metrics to assess sensorimotor deficits, and relevant clinical studies. We subsequently analyse the neurological substrate of VR sensorimotor rehabilitation, with multisensory integration acting as a key element. Finally, we propose a closed-loop patient-centered design recommendation for CIPN sensorimotor rehabilitation. Our aim is to provoke the scientific community toward the development and use of such digital interventions for more efficient and targeted rehabilitation.