In Silico Transcriptomic Expression of MSR1 in Solid Tumors Is Associated with Responses to Anti-PD1 and Anti-CTLA4 Therapies.

Immuno-oncology has gained momentum with the approval of antibodies with clinical activities in different indications. Unfortunately, for anti-PD (L)1 agents in monotherapy, only half of the treated population achieves a clinical response. For other agents, such as anti-CTLA4 antibodies, no biomarkers exist, and tolerability can limit administration. In this study, using publicly available genomic datasets, we evaluated the expression of the macrophage scavenger receptor-A (SR-A) (MSR1) and its association with a response to check-point inhibitors (CPI). MSR1 was associated with the presence of macrophages, dendritic cells (DCs) and neutrophils in most of the studied indications. The presence of MSR1 was associated with macrophages with a pro-tumoral phenotype and correlated with TIM3 expression. MSR1 predicted favorable overall survival in patients treated with anti-PD1 (HR: 0.56, FDR: 1%, p = 2.6 × 10-5), anti PD-L1 (HR: 0.66, FDR: 20%, p = 0.00098) and anti-CTLA4 (HR: 0.37, FDR: 1%, p = 4.8 × 10-5). When specifically studying skin cutaneous melanoma (SKCM), we observed similar effects for anti-PD1 (HR: 0.65, FDR: 50%, p = 0.0072) and anti-CTLA4 (HR: 0.35, FDR: 1%, p = 4.1 × 10-5). In a different dataset of SKCM patients, the expression of MSR1 predicted a clinical response to anti-CTLA4 (AUC: 0.61, p = 2.9 × 10-2). Here, we describe the expression of MSR1 in some solid tumors and its association with innate cells and M2 phenotype macrophages. Of note, the presence of MSR1 predicted a response to CPI and, particularly, anti-CTLA4 therapies in different cohorts of patients. Future studies should prospectively explore the association of MSR1 expression and the response to anti-CTLA4 strategies in solid tumors.

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.

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.

Primary splenic angiosarcoma: a case series of a rare oncological entity and diagnostic challenge.

BACKGROUND AND PURPOSE: Primary angiosarcoma of the spleen (PAS), an exceptionally rare and aggressive neoplasm with high metastatic risk (70%-85%), is frequently diagnosed in an advanced or metastatic stage. It presents diagnostic challenges due to its nonspecific symptomatology and resemblance to benign vascular lesions in various imaging modalities. PATIENTS AND METHODS: This case series aims to clarify the diagnostic difficulties by comparing imaging characteristics (CT-scan, MRI, and [18F]FDG-PET/CT) as well as pathological findings of three PAS cases diagnosed in different stages of the diseases (localized, metastatic, and metastatic with organ failure). Furthermore, a brief review on diagnostic and therapeutic features is included. RESULTS AND INTERPRETATION: We suggest [18F]FDG-PET/CT as a differentiating tool between benign and malignant splenic lesions and propose a flowchart of a diagnostic algorithm for PAS. For treatment, we advocate for early splenectomy and when systemic therapy is warranted, paclitaxel emerges as a viable first-line option. While it is crucial to acknowledge that further trial data is required to evaluate the efficacy of emerging treatment regimens, designing and conducting trials for PAS is challenging given its scarcity and aggressive behavior. Therefore case reporting remains important.

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.

Remote Monitoring and Data Collection for Decentralized Clinical Trials.

Importance: Less than 5% of patients with cancer enroll in a clinical trial, partly due to financial and logistic burdens, especially among underserved populations. The COVID-19 pandemic marked a substantial shift in the adoption of decentralized trial operations by pharmaceutical companies. Objective: To assess the current global state of adoption of decentralized trial technologies, understand factors that may be driving or preventing adoption, and highlight aspirations and direction for industry to enable more patient-centric trials. Design, Setting, and Participants: The Bloomberg New Economy International Cancer Coalition, composed of patient advocacy, industry, government regulator, and academic medical center representatives, developed a survey directed to global biopharmaceutical companies of the coalition from October 1 through December 31, 2022, with a focus on registrational clinical trials. The data for this survey study were analyzed between January 1 and 31, 2023. Exposure: Adoption of decentralized clinical trial technologies. Main Outcomes and Measures: The survey measured (1) outcomes of different remote monitoring and data collection technologies on patient centricity, (2) adoption of these technologies in oncology and all therapeutic areas, and (3) barriers and facilitators to adoption using descriptive statistics. Results: All 8 invited coalition companies completed the survey, representing 33% of the oncology market by revenues in 2021. Across nearly all technologies, adoption in oncology trials lags that of all trials. In the current state, electronic diaries and electronic clinical outcome assessments are the most used technology, with a mean (SD) of 56% (19%) and 51% (29%) adoption for all trials and oncology trials, respectively, whereas visits within local physician networks is the least adopted at a mean (SD) of 12% (18%) and 7% (9%), respectively. Looking forward, the difference between the current and aspired adoption rate in 5 years for oncology is large, with respondents expecting a 40% or greater absolute adoption increase in 8 of the 11 technologies surveyed. Furthermore, digitally enabled recruitment, local imaging capabilities, and local physician networks were identified as technologies that could be most effective for improving patient centricity in the long term. Conclusions and Relevance: These findings may help to galvanize momentum toward greater adoption of enabling technologies to support a new paradigm of trials that are more accessible, less burdensome, and more inclusive.

The Association of Oncology Provider Density With Black-White Disparities in Cancer Mortality in US Counties.

BACKGROUND: Black-White racial disparities in cancer mortality are well-documented in the US. Given the estimated shortage of oncologists over the next decade, understanding how access to oncology care might influence cancer disparities is of considerable importance. We aim to examine the association between oncology provider density in a county and Black-White cancer mortality disparities. METHODS: An ecological study of 1048 US counties was performed. Oncology provider density was estimated using the 2013 National Plan and Provider Enumeration System data. Black:White cancer mortality ratio was calculated using 2014-2018 age-standardized cancer mortality rates from State Cancer Profiles. Linear regression with covariate adjustment was constructed to assess the association of provider density with (1) Black:White cancer mortality ratio, and (2) cancer mortality rates overall, and separately among Black and White persons. RESULTS: The mean Black:White cancer mortality ratio was 1.12, indicating that cancer mortality rate among Black persons was on average 12% higher than that among White persons. Oncology provider density was significantly associated with greater cancer mortality disparities: every 5 additional oncology providers per 100 000 in a county was associated with a .02 increase in the Black:White cancer mortality ratio (95% CI: .007 to .03); however, the unexpected finding may be explained by further analysis showing that the relationship between oncology provider density and cancer mortality was different by race group. Every 5 additional oncologists per 100 000 was associated with a 1.6 decrease per 100 000 in cancer mortality rates among White persons (95% CI: -3.0 to -.2), whereas oncology provider density was not associated with cancer mortality among Black persons. CONCLUSION: Greater oncology provider density was associated with significantly lower cancer mortality among White persons, but not among Black persons. Higher oncology provider density alone may not resolve cancer mortality disparities, thus attention to ensuring equitable care is critical.

Our study provides timely information to address the growing concern about the need to increase oncology supply and the impact it might have on racial disparities in cancer outcomes. This analysis of counties across the US is the first study to estimate the association of oncology provider density with Black-White racial disparities in cancer mortality. We show that having more oncology providers in a county is associated with significantly lower cancer mortality among the White population, but is not associated with cancer mortality among the Black population, thereby leading to a disparity. Our findings suggest that having more oncology providers alone may be insufficient to overcome existing disadvantages for Black patients to access and use high-quality cancer care. These findings have important implications for addressing racial disparities in cancer outcomes that are persistent and well-documented in the US.

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.

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.

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.

[Patient motivation and prehabilitation: assessment often overlooked]. / Motivation du patient et préhabilitation : l'évaluation souvent oubliée.

Prehabilitation, which is still in its infancy, is becoming an essential part of oncology treatment. Motivation assessment is crucial for adherence to these programs, which aim to optimize functional capacity before and during the intensive phases of treatment. To date, healthcare teams have had little experience of assessing motivation, which is a weakness in the care strategy. This is partly due to a lack of standardized models and a delay in caregivers changing their position in response to changes in patient' motivations. In this article, we invite to discuss the 'why' and 'how' of motivational assessment in patients undergoing prehabilitation.

[Prehabilitation through physical activity in oncology]. / Préhabilitation par l'activité physique en oncologie.

It has now been established that preoperative physical activity plays an essential role in minimizing postoperative complications. Patients who have undergone physical preparation recover their preoperative abilities more quickly. However, only about a third of those with access to such preparation report an improvement in their physical abilities. The modalities of intervention and follow-up, such as the training load and the generic format of the proposed sessions, seem to hinder patient participation in these programs, thus explaining the mixed results. In this context, it seems necessary to individualize prehabilitation in order to improve the functional capacities of people in this phase or in the phase of accelerated recovery after treatment or surgery.

The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions.

In cancer treatment, the recurrent challenge of inducing apoptosis through conventional therapeutic modalities, often thwarted by therapy resistance, emphasizes the critical need to explore alternative cell death pathways. Ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides on cellular membranes, has emerged as one such promising frontier in oncology. Induction of ferroptosis not only suppresses tumor growth but also holds potential for augmenting immunotherapy responses and surmounting resistance to existing cancer therapies. This review navigates the role of ferroptosis in tumor suppression. Furthermore, we delve into the complex role of ferroptosis within the tumor microenvironment and its interplay with antitumor immunity, offering insights into the prospect of targeting ferroptosis as a strategic approach in cancer therapy.

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.