From Base Pairs to City Squares: Comprehensive Precision Oncology for the Future.

SUMMARY: An increased understanding of the role of the social determinants of health in cancer prevention, cancer care, and outcomes can lead to their integration into genetics and genomics as well as informing interventions and clinical trials, creating a comprehensive precision oncology framework.

The Biden Cancer Moonshot: American Progress, Global Commitment.

SUMMARY: The Biden Cancer Moonshot is mobilizing efforts toward achieving two clear goals that President Joe Biden and First Lady Jill Biden set: prevent more than 4 million cancer deaths by 2047 and improve the experience of people who are touched by cancer. To achieve these ambitious but achievable goals, the Biden Cancer Moonshot is driving progress across the cancer journey utilizing all facets of the oncology community - federal agencies, and departments, private companies, healthcare providers, patient groups, and philanthropies - to end cancer as we know it here in the United States and all around the world.

The Cancer Spectrum Theory.

SUMMARY: Biological characteristics of tumors are heterogeneous, forming spectra in terms of several factors such as age at onset, anatomic spatial localization, tumor subtyping, and the degree of tumor aggressiveness (encompassing a neoplastic property spectrum). Instead of blindly using dichotomized approaches, the application of the multicategorical and continuous analysis approaches to detailed cancer spectrum data can contribute to a better understanding of the etiology of cancer, ultimately leading to effective prevention and precision oncology. We provide examples of cancer spectra and emphasize the importance of integrating the cancer spectrum theory into large-scale population cancer research.

Precision Endpoints for Contemporary Precision Oncology Trials.

SUMMARY: Traditional endpoints such as progression-free survival and overall survival do not fully capture the pharmacologic and pharmacodynamic effects of a therapeutic intervention. Incorporating mechanism-driven biomarkers and validated surrogate proximal endpoints can provide orthogonal readouts of anti-tumor activity and delineate the relative contribution of treatment components on an individual level, highlighting the limitation of solely relying on aggregated readouts from clinical trials to facilitate go/no-go decisions for precision therapies.

Central venous access device terminologies, complications, and reason for removal in oncology: a scoping review.

BACKGROUND: Lack of agreed terminology and definitions in healthcare compromises communication, patient safety, optimal management of adverse events, and research progress. The purpose of this scoping review was to understand the terminologies used to describe central venous access devices (CVADs), associated complications and reasons for premature removal in people undergoing cancer treatment. It also sought to identify the definitional sources for complications and premature removal reasons. The objective was to map language and descriptions used and to explore opportunities for standardisation. METHODS: A systematic search of MedLine, PubMed, Cochrane, CINAHL Complete and Embase databases was performed. Eligibility criteria included, but were not limited to, adult patients with cancer, and studies published between 2017 and 2022. Articles were screened and data extracted in Covidence. Data charting included study characteristics and detailed information on CVADs including terminologies and definitional sources for complications and premature removal reasons. Descriptive statistics, tables and bar graphs were used to summarise charted data. RESULTS: From a total of 2363 potentially eligible studies, 292 were included in the review. Most were observational studies (n = 174/60%). A total of 213 unique descriptors were used to refer to CVADs, with all reasons for premature CVAD removal defined in 84 (44%) of the 193 studies only, and complications defined in 56 (57%) of the 292 studies. Where available, definitions were author-derived and/or from national resources and/or other published studies. CONCLUSION: Substantial variation in CVAD terminology and a lack of standard definitions for associated complications and premature removal reasons was identified. This scoping review demonstrates the need to standardise CVAD nomenclature to enhance communication between healthcare professionals as patients undergoing cancer treatment transition between acute and long-term care, to enhance patient safety and rigor of research protocols, and improve the capacity for data sharing.

Envisioning Academic Global Oncologists: Proposed Competencies for Global Oncology Training From ASCO.

Recognizing the rising incidence, prevalence, and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has committed to expanding its engagement at a global level. In 2017, the ASCO Academic Global Oncology Task Force sought to define the potential role for ASCO in supporting global oncology as an academic field. A set of recommendations to advance the status of global oncology as an academic discipline were created through a consensus-based process involving participation by a diverse group of global oncology and global health practitioners; these recommendations were then published. The recommendations included developing a set of global oncology competencies for trainees and faculty interested in a career in academic global oncology. Here, we describe the global oncology competencies developed by this task force. These competencies consist of knowledge and skills needed in general global health as well as cancer-specific care and research, including understanding global cancer health disparities, defining unique resources and needs in low- and middle-resource settings, and promoting international collaboration. Although the competencies were originally developed for US training programs, they are intended to be widely applicable globally. By formalizing the training of oncologists and supporting career pathways in the field of global oncology, we can make progress in achieving global equity in cancer care and control.

Exercise oncology clinical trials during treatments: a commentary to address the safety concerns of human subjects regulatory reviewers and committees.

Exercise oncology clinical trials contribute to the advancement of our scientific knowledge and to the safety and care of patients diagnosed with cancer. Nevertheless, regulatory reviewers and committees may not be familiar with the well-documented long-term health benefits and safety of the regular practice of physical activity. Moreover, they may not see how the benefits outweigh the risks in the context where patients diagnosed with cancer are typically seen as vulnerable. Therefore, we would like to provide a purpose-built overview of exercise oncology clinical trials for members involved in institutional review committees, including the Scientific Review Committee (SRC), the Institutional Review Board (IRB), and the Data Safety Monitoring Committee (DSMC) to facilitate a greater understanding of the safety and benefits of physical activity during cancer treatments. Communication is key to improve the success of exercise oncology clinical trials, which are vital for patients diagnosed with cancer.

Tumor Size Is Not Everything: Advancing Radiomics as a Precision Medicine Biomarker in Oncology Drug Development and Clinical Care. A Report of a Multidisciplinary Workshop Coordinated by the RECIST Working Group.

Radiomics, the science of extracting quantifiable data from routine medical images, is a powerful tool that has many potential applications in oncology. The Response Evaluation Criteria in Solid Tumors Working Group (RWG) held a workshop in May 2022, which brought together various stakeholders to discuss the potential role of radiomics in oncology drug development and clinical trials, particularly with respect to response assessment. This article summarizes the results of that workshop, reviewing radiomics for the practicing oncologist and highlighting the work that needs to be done to move forward the incorporation of radiomics into clinical trials.

Concordance in Molecular Tumor Board Case Reviews in the ASCO TAPUR Study.

PURPOSE: With the advent of precision medicine, molecular tumor boards (MTBs) were established to interpret genomic results and guide decision making for targeted therapy in oncology patients. There are currently no universal guidelines for how MTBs should operate and thus variance can be seen depending on which MTB is reviewing the case. This study assesses the concordance of MTB recommendations when a participant case is reviewed by two different MTBs, establishes potential reasons for discordance, and advocates for the establishment of standard MTB operating guidelines. PATIENTS AND METHODS: Participants with advanced cancer, who had exhausted all standard treatment options were screened for the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. Cases were submitted for MTB review if the treatment proposal was outside the protocol genomic matching rules, or if multiple treatment options were identified. Of the 306 cases submitted for review by the TAPUR MTB from 2016 to 2018, 107 were randomly selected for secondary review by a different MTB group. Recommendations from the original review were not disclosed. Concordance between MTB group recommendations was assessed. Concordance was defined as agreement between MTB reviews on the genomic alteration and study drug match proposed by the clinical site. Thematic qualitative analysis was conducted for the discordant cases to assess reasons for discordance. RESULTS: Complete or partial concordance was observed in 79% of cases (95% CI, 70 to 86; one-sided P = .25). Most discordant analyses were due to disagreements on the strength of evidence regarding efficacy of the proposed treatment (32%). CONCLUSION: When presented with identical participant cases, different MTB review groups make the same or similar treatment recommendations approximately 80% of the time.

[Gastrointestinal tumour prevention strategies]. / Präventionsstrategien gastrointestinaler Tumoren.

Over the past few decades, substantial advancements have been achieved in the early detection and treatment of gastrointestinal oncological diseases. The survival rates of patients have significantly improved due to the expansion and enhancement of therapeutic and diagnostic options, leading to modifications in (neo-)adjuvant, perioperative, and palliative strategies, as well as the advent of personalized molecular therapy. Noteworthy progress has also been observed in primary, secondary, and tertiary prevention domains.Despite these advancements, gastrointestinal tumours continue to be a global health burden, with approximately 4 million new cases diagnosed annually. These constitute over a quarter of all tumour cases, with nearly one-third of all global tumour-related mortalities attributed to gastrointestinal tumours.Emerging evidence implicates aberrant differentiation of stem or progenitor cells in the pathogenesis of gastrointestinal tumour diseases. A confluence of clinically recognized risk factors, including high-fat diet, bile acid, microbiome alterations, and host factors, can instigate chronic inflammation. This disrupts stem cell homeostasis and precipitates malignant transformation. Consequently, environmental inflammation emerges as a critical risk factor warranting consideration in clinical cancer prevention and surveillance strategies.This review encapsulates the current understanding and recommendations in the prevention of selected gastrointestinal tumours, aiming to facilitate their integration into clinical practice. It underscores the need for continued research to further refine diagnostic and therapeutic strategies and improve patient outcomes.

[The use of targeted therapies in gastrointestinal oncology]. / Zielgerichtete Therapien in der gastrointestinalen Onkologie.

In recent years, several drugs have been approved that specifically target molecular changes in tumour cells. For patients with gastrointestinal cancer, this has contributed to a significant improvement in prognosis. This article provides an overview of the currently available treatment options and the underlying biomarkers of their mechanisms of action.The evaluation of biomarkers and the use of targeted therapeutics have now become standard care in gastrointestinal oncology. Beyond the molecular-targeted therapy options already approved in the European Union, there is a multitude of additional drugs and biomarkers available, which can also be used outside of formal approval (so-called off-label use). Examples of this are also discussed in this overview (e.g., HER2-targeted therapy for cholangiocarcinoma, the use of KRASG12C inhibitors, or checkpoint inhibition in microsatellite unstable ductal pancreatic carcinoma).The question whether the use of one of these therapeutics represents a possible treatment option for patients with gastrointestinal cancers is typically discussed in a Molecular Tumour Board after undergoing guideline-appropriate therapies.

[Exploration and practice of cardio-oncology].

With the improvement of oncology diagnosis and treatment, the survival time of cancer patients has been significantly prolonged, and the cancer therapy-related cardiovascular toxicity such as radiotherapy, chemotherapy, immunotherapy, and surgery are becoming more and more prominent, and it is in this context that the germ of Cardio-Oncology exploration has come into being. The multidisciplinary Cardio-Oncology team aims to establish a multidisciplinary prevention and control system to assess patients' baseline risk factors, individualized monitoring, and weighing the risk-benefit ratio of cancer therapy. At present, the connotation of the discipline of Cardio-Oncology has been expanded horizontally and deepened vertically in China, and Cardio-Oncology treatment centers have blossomed all over the country. Moreover, international and domestic scholars continue to improve Cardio-Oncology guidelines and consensus through their own practice, and develop artificial intelligence software to help the development of the discipline. It is believed that in the future, with the training of Cardio-Oncologists and the output of high-quality clinical research evidence, cardiovascular safety of cancer patients can be ensured more scientifically and effectively.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

Biological Basis of Breast Cancer-Related Disparities in Precision Oncology Era.

Precision oncology is based on deep knowledge of the molecular profile of tumors, allowing for more accurate and personalized therapy for specific groups of patients who are different in disease susceptibility as well as treatment response. Thus, onco-breastomics is able to discover novel biomarkers that have been found to have racial and ethnic differences, among other types of disparities such as chronological or biological age-, sex/gender- or environmental-related ones. Usually, evidence suggests that breast cancer (BC) disparities are due to ethnicity, aging rate, socioeconomic position, environmental or chemical exposures, psycho-social stressors, comorbidities, Western lifestyle, poverty and rurality, or organizational and health care system factors or access. The aim of this review was to deepen the understanding of BC-related disparities, mainly from a biomedical perspective, which includes genomic-based differences, disparities in breast tumor biology and developmental biology, differences in breast tumors' immune and metabolic landscapes, ecological factors involved in these disparities as well as microbiomics- and metagenomics-based disparities in BC. We can conclude that onco-breastomics, in principle, based on genomics, proteomics, epigenomics, hormonomics, metabolomics and exposomics data, is able to characterize the multiple biological processes and molecular pathways involved in BC disparities, clarifying the differences in incidence, mortality and treatment response for different groups of BC patients.

Managing the Risk of Foodborne Infections in Pediatric Patients with Cancer: Is the Neutropenic Diet Still an Option?

Infections pose a significant threat to morbidity and mortality during treatments for pediatric cancer patients. Efforts to minimize the risk of infection necessitate preventive measures encompassing both environmental and host-focused strategies. While a substantial number of infections in oncologic patients originate from microorganisms within their native microbiological environment, such as the oral cavity, intestines, and skin, the concrete risk of bloodstream infections linked to the consumption of contaminated food and beverages in the community cannot be overlooked. Ensuring food quality and hygiene is essential to mitigating the impact of foodborne illnesses on vulnerable patients. The neutropenic diet (ND) has been proposed to minimize the risk of sepsis during neutropenic periods. The ND aims to minimize bacterial entry into the gut and bacterial translocation. However, a standardized definition for ND and consensus guidelines for specific food exclusions are lacking. Most centers adopt ND during neutropenic phases, but challenges in achieving caloric intake are common. The ND has not demonstrated any associated benefits and does not ensure improved overall survival. Consequently, providing unified and standardized food safety instructions is imperative for pediatric patients undergoing hematopoietic cell transplantation (HCT). Despite the lack of evidence, ND is still widely administered to both pediatric and adult patients as a precautionary measure. This narrative review focuses on the impact of foodborne infections in pediatric cancer patients and the role of the ND in comparison to food safety practices in patients undergoing chemotherapy or HCT. Prioritizing education regarding proper food storage, preparation, and cooking techniques proves more advantageous than merely focusing on dietary limitations. The absence of standardized guidelines underscores the necessity for further research in this field.

[Comparative pathology in oncology-Best practice]. / Vergleichende Pathologie in der onkologischen Forschung.

Comparative experimental pathology is a research field at the interface of human and veterinary medicine. It is focused on the comparative study of similarities and differences between spontaneous and experimentally induced diseases in animals (animal models) compared to human diseases. The use of animal models for studying human diseases is an essential component of biomedical research. Interdisciplinary teams with species-specific expertise should collaborate wherever possible and maintain close communication. Mutual openness, cooperation, and willingness to learn form the basis for a fruitful collaboration. Research projects jointly led by or involving both animal and human pathologists make a significant contribution to high-quality biomedical research. Such approaches are promising not only in oncological research, as outlined in this article, but also in other research areas where animal models are regularly used, such as infectiology, neurology, and developmental biology.

Breaking Bad Proteins-Discovery Approaches and the Road to Clinic for Degraders.

Proteolysis-targeting chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD), with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focuses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.