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Simple Summary: This paper explores the potential of Very High Energy Electron (VHEE) beams, with energies between 50 and 400 MeV, as a promising option for cancer treatment. VHEE beams combine deep tissue penetration, sharp beam edges, easy manipulation using magnetic components, and cost-effectiveness, making them highly precise and versatile for tumor targeting. They also enable FLASH radiotherapy with VHEE (FLASH-VHEET), which may reduce side effects by sparing healthy tissues while effectively treating deep tumors. However, clinical adoption requires advancements in accelerator technology, treatment planning systems, and validation of treatment protocols. FLASH-VHEET also introduces challenges related to time-dependent dose delivery. This paper reviews recent progress in VHEE research, focusing on dosimetric properties, beam delivery, radiobiological effects, and clinical applications. By addressing these aspects, this study provides a foundation for advancing VHEE therapy towards clinical implementation. The use of very high energy electron (VHEE) beams, with energies between 50 and 400 MeV, has drawn considerable interest in radiotherapy due to their deep tissue penetration, sharp beam edges, and low sensitivity to tissue density. VHEE beams can be precisely steered with magnetic components, positioning VHEE therapy as a cost-effective option between photon and proton therapies. However, the clinical implementation of VHEE therapy (VHEET) requires advances in several areas: developing compact, stable, and efficient accelerators; creating sophisticated treatment planning software; and establishing clinically validated protocols. In addition, the perspective of VHEE to access ultra-high dose–rate regime presents a promising avenue for the practical integration of FLASH radiotherapy of deep tumors and metastases with VHEET (FLASH-VHEET), enhancing normal tissue sparing while maintaining the inherent dosimetric advantages of VHEET. However, FLASH-VHEET systems require validation of time-dependent dose parameters, thus introducing additional technological challenges. Here, we discuss recent progress in VHEET research, focusing on both conventional and FLASH modalities, and covering key aspects including dosimetric properties, radioprotection, accelerator technology, beam focusing, radiobiological effects, and clinical outcomes. Furthermore, we comprehensively analyze initial VHEET in silico studies on coverage across various tumor sites. [ABSTRACT FROM AUTHOR]

Tumors, due to their diversity and heterogeneity, pose a significant threat to human health. Multidrug resistance is a prevalent and grave issue in clinical treatment, resulting in treatment failure and cancer recurrence. This resistance renders conventional drug therapies ineffective, presenting a substantial challenge to human health and medical care. Exploring natural products as potential sources for anti-cancer drugs could lead to the development of innovative and efficacious cancer treatments. This article aims to investigate the health implications of natural products (such as paclitaxel, podophyllotoxin, homoharringtonine, camptothecin, and vinblastine) in the discovery of anti-cancer drugs while discussing the methods and progress made in researching novel anti-cancer drugs derived from natural products. The paper discusses the diversity, intricate structures, and target affinity of natural products along with their structural modification techniques, combination therapies utilization possibilities with prodrugs or nanoparticles. Additionally, considering the escalating multidrug resistance observed in tumors nowadays; certain natural products offer new insights and approaches for discovering effective anti-tumor drugs that are crucial for addressing global public health challenges. The challenges faced by natural products during drug development including issues related to bioavailability toxicity concerns as well as limited resources are examined thoroughly. Potential opportunities current issues along with future challenges are highlighted aiming at facilitating the clinical translation of original anti-cancer drugs using natural products. [ABSTRACT FROM AUTHOR]

This paper is concerned with a free boundary problem modeling tumor growth with time-dependent nutrient supply and inhibitor action. We highlight in this paper that the spatial domain occupied by the tumor is set to be n -dimensional for any n ⩾ 3 , and it is taken into account that the nutrient supply ϕ (t) and the inhibitor injection ψ (t) on the tumor surface are time-varying in this problem. The high-dimensional setting of the problem makes the proof of the existence of radial stationary solutions and the accurate determination of their numbers highly nontrivial, in which we have developed a new method that is different from the previous work by Cui and Friedman [11]. We can give a complete classification of the radial stationary solutions to this problem under different parameter conditions, and also explore the asymptotic behavior of the transient solution for small c : = c 1 + c 2 in the case that ϕ (t) and ψ (t) have finite limits as t → ∞. [ABSTRACT FROM AUTHOR]

In this paper, we study a free boundary problem modeling the growth of 3-dimensional tumor cords. Since tumor cells grow freely in both the longitudinal and cross-sectional directions of blood vessels, the investigation of symmetry-breaking phenomena in both directions is biologically very reasonable. This forces the possible bifurcation value γ m , n to be dependent on two variables m and n. Some monotonicity properties of the possible bifurcation value μ n or μ j obtained in Friedman and Hu (2008) [1] and He and Xing (2023) [2] no longer hold here, which brings a great challenge to the bifurcation analysis. The novelty of this paper lies in determining the order of γ m , n for m 2 + n 2 . Together with periodicity and symmetry, we propose an effective method to avoid the need for the monotonicity of γ m , n. We give symmetry-breaking bifurcation results for every γ m , n > 0. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer initiation is not precisely defined yet. It should be the point of shift from normal/benign to malignant. However, it is still controversial in spite of the abundant accumulation of data on carcinogenesis. Cancer initiation is overviewed here from different viewpoints of genetics, epigenetics, viral/microbial infections, and chronic inflammation. The advent of cancer stem cells is discussed as the point at which a normal cell acquires malignancy. Exposure to radiation and chemicals, oncogenic viruses, microbiomes, and inflammation are the major events of cancer initiation. DNA damage and chromosomal aberrations are classically considered the main causes of cancer. The recent idea of epigenetics is broadening the concept, including the suggestion that oncogenic virus infection disrupts various intracellular signaling cascades. Chronic inflammation was proposed as the origin of cancer in the 19th century, and the molecular level of events has been made clear with scientific development. Much knowledge of cancer initiation has become available for integration into research. Simultaneously, the presence of cancer stem cells has been identified and characterized. However, the point of shift from normal to malignant still appears obscure even when taking cancer stem cells into consideration. From these points of view, the advent of cancer stem cells and cancer initiation are briefly discussed as the points of shift from normal to malignant in this paper. [ABSTRACT FROM AUTHOR]

Oxidative stress represents a pivotal mechanism in the pathogenesis of numerous chronic diseases. The Kelch-like ECH-associated protein 1–transcription factor NF-E2 p45-related factor 2 (KEAP1–NRF2) pathway plays a crucial role in maintaining redox homeostasis and regulating a multitude of biological processes such as inflammation, protein homeostasis, and metabolic homeostasis. In this paper, we present the findings of recent studies on the KEAP1–NRF2 pathway, which have revealed that it is aberrantly regulated and induces oxidative stress injury in a variety of diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, respiratory diseases, digestive diseases, and cancer. Given this evidence, targeting KEAP1–NRF2 represents a highly promising avenue for developing therapeutic strategies for chronic diseases, and thus the development of appropriate therapeutic strategies based on the targeting of the NRF2 pathway has emerged as a significant area of research interest. This paper highlights an overview of current strategies to modulate KEAP1–NRF2, as well as recent advances in the use of natural compounds and traditional Chinese medicine, with a view to providing meaningful guidelines for drug discovery and development targeting KEAP1–NRF2. Additionally, it discusses the challenges associated with harnessing NRF2 as a therapeutic target. [ABSTRACT FROM AUTHOR]

Distinguishing tumours from other conditions is a primary challenge in paediatric neuro-radiology. This paper aims to describe mimics, which are non-neoplastic conditions that have features similar to a neoplastic process caused by a non-neoplastic entity, and chameleons, which are uncommon presentations of brain tumours that are mistaken for other diagnoses. By doing so, we aim to raise awareness of these conditions and prevent inappropriate investigations or treatment in children. When suspecting a brain tumour, a detailed history, physical examination, and appropriate laboratory investigations can provide important clues about the nature of the lesion and narrow the list of possible differential diagnoses. Presented here is a collection of cases that have puzzled us for various reasons, including the absence of symptoms, coincidental timing, or misleading radiological features. Included in this pictorial essay are cases in which only a biopsy has helped us to make the correct diagnosis, as well as cases in which an unsuccessful biopsy has allowed us to evaluate hypotheses that were previously unaddressed. The paper also highlights the limited knowledge we have about the intercausality between malformations and later onset tumours, and the spectrum of manifestations that metabolic and genetic disorders can have. Key points: When making an oncological radiological diagnosis in children, there are several additional factors to consider compared to adults. This is particularly true due to the extreme histopathological heterogeneity. Children can present with mass-forming lesions caused by various conditions, including inflammatory, infectious, demyelinating, or malformative aetiologies. In some cases, MRI features can significantly overlap, making it challenging to initiate appropriate therapy based on imaging data. The lack of contrast enhancement or restricted diffusion does not always indicate a non-neoplastic cause or a less clinically aggressive tumour. A timely and minimally invasive biopsy may be necessary to confirm the presence of pathology that is not certain on MRI and to provide appropriate treatment for the child's illness. MR spectroscopy, perfusion-weighted imaging and Amid Proton Transfer weighted imaging can aid in distinguishing between treatment-related features and relapses, and between inflammatory processes and tumours, if used and interpreted correctly. [ABSTRACT FROM AUTHOR]

Nurses in all specialties have been called upon to take action to address global climate change, climate justice, and health. The American Nurses Association (2023) has specifically tasked nursing professional organizations to (a) educate members on climate change–related illnesses and negative impacts on treatment, (b) collaborate with grassroots organizations for environmental justice efforts, (c) support policies that promote climate mitigation and adaptation, (d) maintain familiarity with climate justice frameworks, and (e) collectively amplify the voice of nursing to strengthen its impact on climate policy. The purpose of this white paper is to enlighten members of the Oncology Nursing Society and oncology nurses at large on the increasing impact of climate change across the cancer control continuum and the pivotal role of the oncology nurse in education, research, clinical practice, and advocacy. Climate change refers to long-term shifts in temperature and weather patterns that are occurring because of global warming (United Nations, n.d.). Climate change is an often-overlooked social determinant of (or contributor to) health that exacerbates poor health, increases healthcare costs, disproportionately affects some communities, and has a synergistic effect with other social determinants of health (Ragavan et al., 2020). Climate change affects all aspects of the cancer control continuum and impacts some populations disproportionately Events such as wildfires and floods, exacerbated by climate change, can heighten individuals’ exposure to cancer-causing substances, thereby increasing their susceptibility to the disease; reducing such exposure can reduce risks for cancer and positively impact the environment. Air pollution, extended droughts, heat waves, ultraviolet radiation, extreme weather events, and food supply disruptions also impact cancer etiology. Extreme weather events disrupt preventive care, cancer detection, and screening efforts, and create workforce shortages that can lead to suboptimal care. Disruptions in the supply chain and scheduled healthcare visits impact patient care continuity. Additionally, climate-related extreme weather events have an impact on overall survival and disrupt end-of-life care, underscoring the pervasive impact of climate change on cancer care across the continuum. Oncology nurses are strategically positioned to contribute to multifaceted solutions, including obtaining and offering education to fellow healthcare providers, students, patients, community members, and policymakers. Oncology nurse scientists are equipped to spearhead the generation of pertinent new knowledge, and nurses in clinical care can play a crucial role in assisting their healthcare system to become carbon net neutral. Oncology nurses must answer the call to actively engage in climate and health advocacy efforts within their own healthcare systems and in the communities where they live, work, and play. Several resources for education and action are shared. [ABSTRACT FROM AUTHOR]

Genomics plays an essential role in the early detection, classification, and targeted cancer therapy based on the analysis of precise alterations at the molecular level. Using the most reliable approach is essential for the exact interrogation and cross-examination of complex and multi-high-dimensional “Multi-omics” cancer genomics data. In recent years, deep learning has been successfully utilized to deal with large cancer genomics data and has the potential to transform predictive biology. This review aims to explore the recent advancements in the application of deep learning models in basic cancer omics research, including different methodologies for the interrogation of bulk cancer omics data and the importance of cross-platform data integration. The paper provides insights into advantages, limitations, potential for improvement, research gaps, future direction, and an in-depth comparison of the models currently used in the field of cancer genomics, highlighting the crucial need for collaboration and interdisciplinary research in the field. [ABSTRACT FROM AUTHOR]

Simple Summary: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a crucial role in cancer development. However, due to their diverse cellular functions, the mechanisms by which they drive cancer are complex. In this review, we discuss the mechanisms of action of FGFs and FGFRs, as well as how the dysregulation of FGF signaling contributes to cancer in various tumor types. The complexity of FGF signaling is partly explained by the large number of FGF isoforms and FGFR receptor types. We provide a classification of FGF ligands based on their signaling modes and binding specificity to FGFRs. Additionally, we explore promising therapeutic strategies being developed to target FGF signaling in oncology, including small molecules, ligand traps, and monoclonal antibody-based inhibitors. Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 subfamily is particularly interesting because of its unique protein structure and role in endocrine function. The abnormal expression of FGFs in different cancer types (breast, colorectal, hepatobiliary, bronchogenic, and others) is examined and correlated with patient prognosis. The classification of FGF ligands based on their mode of action, whether autocrine, paracrine, endocrine, or intracrine, is illustrated, and an analysis of the binding specificity of FGFs to FGFRs is also provided. Moreover, the latest advances in cancer therapeutic strategies involving small molecules, ligand traps, and monoclonal antibody-based FGF inhibitors are presented. Lastly, we discuss how the dysregulation of FGF and FGFR expression affects FGF signaling and its role in cancer development. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent scientific evidence has revealed that microbiota composed of mycoplasma, bacteria, fungi, viruses, and other microbes inhabit the human body in its various tissues and organs and that these microorganisms have many roles in human physiology and pathology. The gut microbiota is the most widely studied so far, and its nature has been clearly correlated with a number of various physiological and pathological conditions, as well as responses to various therapies. Even tumors have their own microbiota, which conditions their pathological traits, immunological profile, and response to therapies. Strategies to combat tumors should therefore rationally take into account their microbial composition. Among a vast variety of available tools to manipulate the microbiota in the human body, antibiotic molecules are an obvious possibility. Some of them have recognized direct effects on microbes but also on human cells and cancer cells in particular. This paper aims to review relevant preclinical and clinical data about the antitumor properties of common antibiotics (excluding specific anticancer antibiotics) and their interactions with current standard anticancer therapies, in order to provide researchers with a tool for designing novel experiments and clinical trials. Intratumoral microbiota, the diverse community of microorganisms residing within tumor tissues, represent an emerging and intriguing field in cancer biology. These microbial populations are distinct from the well-studied gut microbiota, offering novel insights into tumor biology, cancer progression, and potential therapeutic interventions. Recent studies have explored the use of certain antibiotics to modulate intratumoral microbiota and enhance the efficacy of cancer therapies, showing promising results. Antibiotics can alter intratumoral microbiota's composition, which may have a major role in promoting cancer progression and immune evasion. Certain bacteria within tumors can promote immunosuppression and resistance to therapies. By targeting these bacteria, antibiotics can help create a more favorable environment for chemotherapy, targeted therapy, and immunotherapy to act effectively. Some bacteria within the tumor microenvironment produce immunosuppressive molecules that inhibit the activity of immune cells. The combination of antibiotics and other cancer therapies holds significant promise for creating a synergistic effect and enhancing the immune response against cancer. In this review, we analyze several preclinical studies that have been conducted to demonstrate the synergy between antibiotics and other cancer therapies and discuss possible clinical implications. [ABSTRACT FROM AUTHOR]

Purpose: The research was designed to help our understanding of the relationship between care-recipient health and caregiver well-being. Design: To achieve this goal, we followed the measurement development steps outlined by Hinkin. We began by identifying 18 care-recipient health conditions that encapsulated the breath of caregiver duties pertaining to specific recipient health conditions. Methods: Using a sample of n = 1696 employed caregivers, we then developed and empirically validated a research instrument that allows researchers and practitioners to (1) identify whether the caregiver was providing care to an individual who suffered from one or more of 18 health conditions and (2) quantify the demands imposed on the caregiver of caring for someone with this health issue. Results: Factor analysis identified four different constructs each of which measures the demands placed on the caregiver of caring for someone suffering from several closely related health conditions: problems with daily functioning, mental health problems, cardiovascular problems, and cancer/immune system issues. [ABSTRACT FROM AUTHOR]

Cancer is a very complex phenomenon that involves many different scales and situations. In this paper, we consider a free boundary problem describing the evolution of a tumor colony and we derive a new asymptotic model for tumor growth. We focus on the case of a single phase tumor colony taking into account chemotactic effects in an early stage where there is no necrotic inner region. Thus, our model is valid for the case of multilayer avascular tumors with very little access to both nutrients and inhibitors or the case where the amount of nutrients and inhibitors is very similar to the amount consumed by the multilayer tumor cells. Our model takes the form of a single nonlocal and nonlinear partial differential equation for the interface of the multilayer tumor colony. Our model is able to capture chemotactic and cohesion effects and also the effect of nutrients, inhibitors and vasculation of the tumor colony. Besides deriving the model, we also prove a well-posedness result. [ABSTRACT FROM AUTHOR]

Introduction Peri-operative medicine is becoming increasingly relevant in the context of managing frail patients with cancer. This paper outlines how demographic shifts in populations are affecting cancer incidence and frailty rates, the relevance this holds to the management of cancer care, and the outcome measures that should be used to gauge best clinical practice to ensure patient-centred care. Methods A targeted literature review was conducted using the search terms 'surgical oncology', 'outcomes', 'frailty', 'quality of life' and 'end of life' from 10 to 17 June 2024. Articles were reviewed by all authors and core themes from the literature review were identified. Core themes were then discussed by the authors to construct a narrative review. Results The review identified several core themes in relation to patient-centred outcome measures for oncological surgery. The UK population is ageing and consequently, the number of older people being diagnosed with cancer is increasing. There is much evidence to show that older patients have poorer outcomes in terms of mortality and postoperative complications across all types and severities of cancer. Traditional outcome measures such as 30-day mortality, duration of stay and recurrence rates fail to capture the outcomes that are most pertinent to this patient cohort. These include patient quality of life and treatment burden. We discuss the measurement of quality of life through the use of patient-reported outcome measures and their limitations. We also highlight the need for patient-centred, holistic care with the use of tools such as comprehensive geriatric assessment, which have been shown to improve patient outcomes. Discussion There is need for a greater emphasis on quality-of-life measures alongside mortality and patient-reported outcome measures. We argue that holistic care approaches should play a greater role in enabling the measurement of outcome states beyond simply dead or alive. [ABSTRACT FROM AUTHOR]

Introduction Oncoanaesthesia is a specialised branch of anaesthesia dedicated to enhancing outcomes, prioritising patient safety and improving the overall care of patients with cancer during surgery. We outline the global epidemiology of cancer, emphasising the necessity for this subspecialty, and discuss the criteria supporting its establishment. Methods We performed searches of electronic databases to identify relevant peer-reviewed publications. The search was designed to capture a wide range of study types, including randomised controlled trials; retrospective studies; meta-analyses; and systematic reviews. The titles and abstracts were screened to identify publications relevant to oncoanaesthesia, cancer recurrence and return to intended therapy. The reference lists were manually reviewed to identify relevant papers for consideration. Results This review highlights the growth of oncoanaesthesia over the past decade. Research opportunities abound in areas such as: the impact of anaesthesia on cancer recurrence; the use of enhanced recovery after surgery programmes; patient blood management; peri-operative nutrition; techniques for modulating peri-operative inflammatory responses; and strategies to reduce the time to return to intended oncological treatment. Discussion By integrating various subspecialties within oncology centres, oncoanaesthesia ensures a thorough and holistic approach to both curative and palliative cancer care, ultimately improving patient outcomes and providing better support for families and caregivers throughout the peri-operative period. [ABSTRACT FROM AUTHOR]

There is mounting interest in the possibility that metformin, indicated for glycemic control in type 2 diabetes, has a range of additional beneficial effects. Randomized trials have shown that metformin prevents adverse cardiovascular events, and metformin use has also been associated with reduced cognitive decline and cancer incidence. In this paper, we dig more deeply into whether metformin prevents cancer by emulating target randomized trials comparing metformin to sulfonylureas as first-line diabetes therapy using data from the Clinical Practice Research Datalink, a UK primary-care database (1987-2018). We included 93 353 individuals with diabetes, no prior cancer diagnosis, no chronic kidney disease, and no prior diabetes therapy who initiated use of metformin (n  = 79 489) or a sulfonylurea (n  = 13 864). In our cohort, the estimated overlap-weighted additive separable direct effect of metformin compared with sulfonylureas on cancer risk at 6 years was −1 percentage point (95% CI, −2.2 to 0.1), which is consistent with metformin's providing no direct protection against cancer incidence or substantial protection. The analysis faced 2 methodological challenges: (1) poor overlap and (2) precancer death as a competing risk. To address these issues while minimizing nuisance model misspecification, we develop and apply double/debiased machine learning estimators of overlap-weighted separable effects in addition to more traditional effect estimates. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have altered the landscape of tumor immunotherapy, offering novel therapeutic approaches alongside surgery, chemotherapy, and radiotherapy and significantly improving survival benefits. However, their clinical efficacy is limited in some patients, and their use may cause immune-related adverse events (irAEs). Integrating traditional Chinese medicine (TCM) with ICIs has demonstrated the potential to boost sensitization and reduce toxicity. Clinical trials and experimental explorations have confirmed that TCM and its active components synergistically enhance the effectiveness of ICIs. This narrative review summarizes the TCM practices that enhance the clinical efficacy and reduce irAEs of ICIs. This paper also summarizes the mechanism of experimental studies on the synergies of Chinese herbal decoctions, Chinese herbal preparation, and Chinese herbal active ingredients. Most of the studies on TCM combined with ICIs are basic experiments. We discussed the mechanism of TCM enhanced ICIs to provide reference for the research and development of TCM adjuvant immunotherapy. We conducted a literature search using PubMed and Chinese National Knowledge Infrastructure databases, with a focus on herbal decoction, Chinese medicine preparations, and active ingredients that boost the effectiveness of ICIs and reduce irAEs. The search keywords were "ICIs and traditional Chinese medicine", "PD-1 and traditional Chinese medicine", "PD-L1 and traditional Chinese medicine", "CTLA-4 and traditional Chinese medicine", "IDO1 and traditional Chinese medicine", "Tim-3 and traditional Chinese medicine", "TIGIT and traditional Chinese medicine", "irAEs and traditional Chinese medicine". The search period was from May 2014 to May 2024. Articles involving the use of TCM or its components in combination with ICIs and investigating the underlying mechanisms were screened. Finally, 30 Chinese medicines used in combination with ICIs were obtained to explore the mechanism. In the part of immune checkpoint molecules other than PD-1, there were few studies on the combined application of TCM, so studies involving the regulation of immune checkpoint molecules by TCM were included. TCM has been shown to boost the effectiveness of ICIs and reduce irAEs. Researchers indicate that TCM and its active components can work synergistically with ICIs by regulating immune checkpoints PD-1, PD-L1, CTLA-4, and IDO1, regulating intestinal flora, improving tumor microenvironment and more. Combining TCM with ICIs can play a better anti-tumor role, but larger samples and high-quality clinical trials are necessary to confirm this. Many Chinese medicines and their ingredients have been shown to sensitize ICIs in experimental studies, which provides a rich choice for the subsequent development of ICI enhancers. [Display omitted] • Traditional Chinese medicine (TCM) enhances sensitivity and reduces toxicity of immune checkpoint inhibitors (ICIs). • This paper reviews the mechanism of TCM sensitizing ICIs. • Treatment with TCM plus ICIs is worthy of further large-scale clinical study. [ABSTRACT FROM AUTHOR]

Based on fieldwork conducted in China from November 2018 to January 2020 on biomedical innovation with advanced therapies open to foreigners, in this paper I address the question of why parents of children with incurable cancer decide to access experimental treatment on the other side of the world. While work on the "political economy of hope" has already extensively researched the relation between biomedical technology and hope, I delve into other terrains. In this paper, I will discuss the role of "ontological hope" in the moral project of caring for a child with cancer. Drawing on the Anthropology of Ethics, I conclude that in the postgenomic era, when incurable cancers are recategorize as not-yet-treatable, parents' efforts to access experimental treatment highlight the complex moral work that parents must undergo to imagine a future good life despite their irreparable loss. • Accessing experimental treatment can be understood as part of a moral project. • The moral experience of personal misfortune offers new insights on hope and biomedical innovation. • Access to experimental technology might avoid the moral catastrophe of not having done enough. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death globally. Over 70% of the 10 million cancer deaths worldwide in 2020 occurred in low- and middle-income countries. Radiotherapy is an important cancer treatment, used in half of cancer patients. Significant global disparities in radiotherapy access exist, with low access in low- and middle-income countries. The benefits of tele-radiotherapy in low- and middle-income countries for expanding global radiotherapy access are yet to be fully realized. In this paper, we highlight potential applications of tele-radiotherapy in expanding access to high-quality radiotherapy in developing countries. We performed a literature search to retrieve studies involving telemedicine applications in radiotherapy to provide a comprehensive overview of the topic. PubMed database served as the main source for retrieving studies, using the following search terms: ("telemedicine", "radiotherapy", "telehealth", "remote monitoring", "oncology", and "remote training"). Additional selected papers were obtained from Web of Science, and Google Scholar using the same search terms. Telemedicine in radiotherapy has many applications. Virtual training could upgrade radiotherapy skills in low- and middle-income countries, enabling safe adoption of new radiotherapy techniques and quality assurance. Tele-radiotherapy consultations and patient follow-up could improve the efficiency of clinics while tele-radiotherapy planning and peer-review could enable equitable global access to radiotherapy expertise. Telemedicine could also facilitate wider global access to radiotherapy trials. While telemedicine in radiotherapy holds significant promise in improving global radiotherapy access, several barriers to its adoption exist. These include a lack of infrastructure, data security concerns, regulatory challenges, resistance from providers and patients, financial constraints, miscommunication during remote consultations, and lack of training. Tele-radiotherapy applications hold promise in providing solutions to overcome global radiotherapy access inequity but the benefits of tele-radiotherapy in low- and middle-income countries are yet to be fully realized. [ABSTRACT FROM AUTHOR]

Oncologists are faced with choosing the best treatment for each patient, based on the available evidence from randomized controlled trials (RCTs) and observational studies. RCTs provide estimates of the average effects of treatments on groups of patients, but they may not apply in many real-world scenarios where for example patients have different characteristics than the RCT participants, or where different treatment variants are considered. Causal inference defines what a treatment effect is and how it may be estimated with RCTs or outside of RCTs with observational – or 'real-world' – data. In this review, we introduce the field of causal inference, explain what a treatment effect is and what important challenges are with treatment effect estimation with observational data. We then provide a framework for conducting causal inference studies and describe when in oncology causal inference from observational data may be particularly valuable. Recognizing the strengths and limitations of both RCTs and observational causal inference provides a way for more informed and individualized treatment decision-making in oncology. • Treatment effect estimates from randomized controlled trials (RCTs) guide treatment decisions. • RCTs often exclude diverse patient populations and are typically small. • Causal inference helps estimate treatment effects in RCTs or observational data. • This paper provides an intro to causal inference and a framework for causal inference studies. • With causal inference studies, treatment effects can be tailored to individual patients. [ABSTRACT FROM AUTHOR]

Traditional Chinese herbal medicine has unique advantages as anti-cancer drugs and adjuvant therapies. Rabdosia rubescens (Hemsl.) H. Hara (R. rubescens) is a traditional medicinal plant known for its anti-inflammatory, antioxidant, antibacterial, anti-angiogenic and antitumor properties. The antitumor activity of R. rubescens is widely recognized among the folk communities in Henan Province, China. This study reviews the botany, ethnopharmacology, phytochemistry, anti-tumor active ingredients, mechanisms, and clinical applications of R. rubescens , aiming to provide a comprehensive understanding for its use as an anti-cancer drug and adjuvant therapy. We systematically searched the literature in PubMed, Web of Science, and CNKI using the following keywords: "Rabdosia rubescens", "Isodon rubescens", "traditional application", "anti-tumor", "phytochemistry", "anti-tumor active compounds", "oridonin" and "clinical application". The search covered publications from 1997 to 2024. Inclusion criteria included original studies or reviews focusing on the anti-tumor properties of R. rubescens or its active components. Exclusion criteria included studies related to non- R. rubescens applications. R. rubescens is a perennial herbaceous plant in the family Lamiaceae, mainly found in central and southern China. Historically, it has been used to treat conditions such as sore throat, cough, and excess phlegm. The plant contains various compounds, including diterpenes, triterpenes, steroids, flavonoids, phenolic acids, essential oils, amino acids, alkaloids, and polysaccharides, with diterpenes, triterpenes, flavonoids, and phenolic acids being the most active. This review identifies 50 compounds with anti-tumor properties, comprising 34 diterpenes, 2 triterpenes, 7 flavonoids, and 7 phenolic acids. Notably, besides oridonin and ponicidin, the ent-kaurane diterpenoids (20S)-11β,14β,20-trihydroxy-7α,20-epoxy-ent-kaur-16-en15-one and (20S)-11β,14β-dihydroxy-20-ethoxy7α,20-epoxy-ent-kaur-16-en-15-one demonstrate significant anti-tumor activity, attributed to their carbonyl group at C-15, hydroxyl group at C-1, and OEt group at C-20. Mechanistically, R. rubescens combats tumors by blocking the tumor cell cycle, promoting apoptosis, inhibiting cell migration and angiogenesis, inducing ferroptosis, reversing drug resistance, and enhancing radiosensitivity in tumor cells. Clinically, R. rubescens is available in various forms, including tablets, drops, syrups, capsules, and lozenges, and is primarily used for tonsillitis, pharyngitis, and stomatitis. According to the 2020 edition of the Pharmacopoeia of China, R. rubescens tablets are recognized as an adjuvant therapy for cancer. Clinical studies indicate that R. rubescens syrup, tablets, and thermal therapy can enhance cancer patient survival rates and lower tumor recurrence rates. Given its traditional and modern uses, active anti-tumor components, and mechanisms, R. rubescens is a promising resource in traditional Chinese medicine for anti-tumor therapy. To realize its full potential, future research should explore additional active anti-tumor compounds beyond oridonin and ponicidin. For these key components, studies should focus on structural modifications to identify new active molecules and essential anti-tumor structures. Clinically, it is important to investigate how R. rubescens interacts with other Chinese herbs in anti-tumor formulations to enhance treatment efficacy and guide appropriate clinical use. Furthermore, future studies should undergo ethical review and include larger-scale randomized controlled trials to validate the efficacy of R. rubescens in treating tumors, thereby promoting its role as an anti-tumor traditional Chinese medicine. [Display omitted] • The morphology and distribution of Rabdosia rubescens were reviewed. • Summary of 50 antitumor chemical components from Rabdosia rubescens. • The mechanism of antitumor components in Rabdosia rubescens was summarized. • This paper reviews clinical pharmaceutical preparations and research on Rabdosia rubescens. [ABSTRACT FROM AUTHOR]

Collecting large amounts of radiotherapy (RT) data from clinical systems is known to be a challenging task. Still, data collections outside the original RT systems are needed to follow-up on the quality of cancer care and to improve RT. This paper aims to describe how RT data is collected nationally in Denmark and Sweden for this purpose and gives an overview of the stored information in both countries' national data sources. Although both countries have clinical national quality registries with broad coverage and completeness for many cancer diagnoses, some were initiated already in the seventies, and less than one in ten includes quantitative information on RT to a level of detail useful for more than basic descriptive statistics. Detailed RT data can, however, be found in Denmark's DICOM Collaboration (DcmCollab) database, initiated in 2009 and in Sweden's quality registry for RT launched in 2023 (SKvaRT). Denmark has collected raw DICOM data for all patients enrolled in clinical trials, with files being directly and automatically transferred to DcmCollab from the original data sources at each RT centre. Sweden collects aggregated RT data into SKvaRT for all patients undergoing RT in Sweden, with DICOM files being transferred and selected alpha-numeric variables forwarded via a local intermediate storage database (MIQA) at each hospital. In designing their respective solutions, both countries have faced similar challenges regarding which RT variables to collect and how to technically link clinical systems to their data repositories. General lessons about how flexibility currently is balanced with storage requirements and data standards are presented here together with future plans to harvest real-world RT data. • DcmCollab in Denmark and SKvaRT in Sweden are national radiotherapy data collections. • The Danish system favours complete and flexible datasets for research purposes. • The Swedish system favours streamlined datasets focusing on quality improvements. • Each solution stores detailed and standardised radiotherapy data outside the clinical systems. • General lessons on proactive data management in radiotherapy are given by both solutions. [ABSTRACT FROM AUTHOR]

Background: Examining dietary patterns in relation to mortality offers a more comprehensive view of food and nutrient intake. However, to our knowledge, the association of the Korean population's dietary patterns with mortality remains scarce and unclear. We aim to investigate the association between dietary patterns and all-cause, cardiovascular disease (CVD), and cancer mortality in the Korean population. Methods: This prospective cohort study included 18,019 men and 26,604 women aged ≥ 19 years who participated in the Korea National Health and Nutrition Examination Surveys 2007–2015. Dietary data were collected from a 24-hour dietary recall. Mortality from all causes, CVD, and cancer were ascertained from linkage to Statistics Korea. We identified dietary patterns through factor analysis. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the all-cause, CVD, and cancer mortality according to diet pattern scores. Results: During a mean follow-up of 8.19 person-years, 2,622 deaths were identified, with 595 due to CVD and 827 due to cancer. Factor analysis based on 22 food groups, three dietary patterns were obtained: (1) "animal food and condiment pattern," (2) "seafood and vegetable pattern," and (3) "dairy products and processed meat pattern." After multivariable adjustment, the "seafood and vegetable pattern" score was associated with a lower risk of all-cause and CVD mortality. HRs (95% CIs) for all-cause mortality for the second to the highest quintile of "seafood and vegetable pattern", compared with the first quintile were 0.86 (0.75–0.99), 0.75 (0.65–0.87), 0.81 (0.69–0.94), and 0.87 (0.73–1.05), respectively (P for trend = 0.191). For CVD mortality, the HRs were 0.82 (0.62–1.07), 0.80 (0.58–1.08), 0.70 (0.50–0.99), and 0.63 (0.42–0.96), respectively (P for trend = 0.027). No statistically significant associations were found in "animal food and condiment pattern" or "dairy products and processed meat pattern" for all-cause, CVD, and cancer mortality. Conclusions: We observed that the "seafood and vegetable" dietary pattern decreased the risk of all-cause and CVD mortality in Korean adults. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To enhance your understanding of the growing importance of genomics in cancer care • To read about cancer nurses’ views on, and knowledge of, genomics • To consider cancer nurses’ genomics training needs and what forms training could take. Background: Advances in genomic medicine in the NHS have had significant implications for cancer care and cancer nursing. However, it is unclear whether nurses and other healthcare professionals responsible for delivering front-line care feel they have sufficient knowledge and confidence in relation to genomics. Aim: To assess the level of practice-based knowledge of genomics among UK-based cancer nurses. Method: A survey was designed using an online survey platform. The survey reached 474 cancer nurses and 199 of them responded. Data were analysed using the online survey platform, spreadsheets and pivot tables. Findings: Respondents reported low confidence in making decisions involving genomics. Only 27% had ordered a genetic or genomic test and only 39% had contacted their clinical genetics team in the past 12 months. Overall, most respondents reported a need to improve their knowledge of genomics. Conclusion: There was a clear need to improve knowledge about how to order testing and communicate with specialist genetic teams, as well as to clarify the role of the cancer nurse in this process. [ABSTRACT FROM AUTHOR]

Background: Demonstrating mortality reduction in new colorectal cancer (CRC) screening programs through randomized clinical trials (RCTs) is challenging. We systematically reviewed single-round program performance outcomes using a stepwise approach proposed by the World Endoscopy Organization CRC Screening Committee framework. Methods: The MEDLINE, EMBASE, Central, and Ichushi Web databases were searched until October 28, 2024, to find RCTs comparing guaiac-based and immunochemical fecal occult blood testing (gFOBT and FIT), flexible sigmoidoscopy (FS), computed tomographic colonography (CTC), and total colonoscopy (TCS). Paired reviewers screened studies, extracted data, and assessed bias risk. A Bayesian random-effects network meta-analysis was conducted, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. The primary outcome was advanced neoplasia (AN) detection, and the secondary outcomes were participation and colorectal cancer (CRC) detection, all during the first screening round. Results: Eighteen RCTs (437,072 invitees) were included. The risk of bias was low or raised some concerns for screening participation, but it was high for detection outcomes. In the network meta-analysis of 15 RCTs not allowing crossover, the FIT-based program had a higher AN detection rate than the gFOBT-based program (relative risk [RR] 2.48; 95% credible interval [CrI] 1.52–4.21; moderate certainty). AN detection rates were not different in the CTC- (RR 1.01; CrI 0.43–2.23; very low certainty) and TCS-based (RR 1.03; CrI 0.54–1.78; low certainty) programs compared with the FS-based program. All the visualization modality programs had higher AN detection rates than the FIT-based program (FS: RR 2.13 [CrI 1.38–3.77]; CTC 2.16 [1.11–4.51]; and TCS 2.19 [1.43–3.48]; all with low certainty). Low event rates precluded definitive conclusions regarding CRC detection (very low to low certainty). The TCS-based program had the worst participation rate (very low to low certainty). Comparative data allowing crossover were limited. Conclusions: This is the first network meta-analysis that evaluates program-level initial performance indicators. FIT-based programs likely detect more AN cases than gFOBT-based programs, while FS-, CTC-, and TCS-based programs may outperform FIT. Due to limitations in first-round results, long-term outcomes should be assessed after 10–15 years. [ABSTRACT FROM AUTHOR]

Background: ENOPH1 (Enolase-phosphatase 1), a member of the HAD-like hydrolase superfamily, has been linked to a range of physiological conditions, including neurological disorders. However, its involvement in tumorigenesis remains underexplored. This study is the first to conduct a pan-cancer analysis of ENOPH1, aiming to elucidate its role in multiple cancers through various bioinformatics platforms. Methods: We conducted a thorough analysis using data from UCSC databases. ENOPH1 expression in tumor and normal tissues was evaluated using R language software. Survival analyses, genetic alterations, and RNA modifications were assessed through the GEPIA2 and cBioPortal platforms. The relationships between ENOPH1 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) were examined using TIMER2 and R software. ENOPH1-related gene enrichment analysis was performed using the STRING and GEPIA2 databases, followed by Gene Ontology (GO) and KEGG pathway enrichment analyses. Results: ENOPH1 expression was significantly upregulated in various cancers, including ACC, BLCA, BRCA, and COAD. High ENOPH1 expression was associated with poor overall survival (OS) in cancers such as KICH, LIHC, BRCA and LUAD. High ENOPH1 expression was associated with poor disease specific survival (DSS) in cancers such as KICH, LIHC, BRCA and MESO. Genetic alterations of ENOPH1, primarily mutations and deep deletions, were identified in UCEC, BLCA, and OV. ENOPH1 showed significant correlations with RNA modifications (m1A, m5C, m6A), immune checkpoints, and immune modulators across multiple cancer types. ENOPH1 was positively correlated with TMB, MSI, and HRD in cancers like BLCA, BRCA, and STAD. Furthermore, enrichment analysis revealed that ENOPH1 interacts with proteins involved in critical pathways such as AMPK, Hippo, and PI3K-AKT, suggesting its role in cancer progression. Conclusion: This pan-cancer analysis reveals ENOPH1's potential as a prognostic biomarker and its involvement in key signaling pathways across multiple cancers. Our findings provide new insights into the role of ENOPH1 in tumorigenesis and highlight its potential as a therapeutic target in cancer treatment. [ABSTRACT FROM AUTHOR]

Within the fields of oncology practice and research, cancer has historically been and continues to be understood as primarily biologically produced and physiologically driven. This understanding is rooted in biomedicine, the dominant model of health and illness in the Western world. Yet, there is increasing evidence of inequities in cancer that are influenced by social and structural inequities. In this article, we propose that cancer-related inequities ought to be seen as issues of social justice, and, given nursing's longstanding commitments to social justice, they ought to be a priority for oncology nurses. Using a social justice lens, we highlight potential social injustices in the form of inequities in cancer outcomes and access to cancer care across the cancer continuum. Our intention is not to provide an exhaustive review of evidence, but to provide our perspective, adding to the dialogue surrounding health equity and cancer while shifting the narrative away from an understanding of cancer inequities as stemming from "lifestyle" and "behavioural" choices. We conclude by exploring the implications of considering cancer inequities as social injustices for nursing practice. [ABSTRACT FROM AUTHOR]

Adolescents and young adults (AYAs), often defined as those aged 15–39 years, face unique challenges in oncology that are often unmet by conventional care models. This systematic review examines evidence on establishing dedicated AYA oncology units, focusing on logistical, infrastructural, and personnel-related recommendations. A PRISMA-guided search of PubMed (2000–2024) identified seven studies that emphasized early stakeholder involvement and collaboration between pediatric and adult oncology teams to ensure comprehensive care. Multidisciplinary teams (MDTs) of oncologists, nurses, and psychosocial support staff were highlighted as essential to address AYA patients' diverse needs. Care models varied, with some advocating consultation-based services and others supporting dedicated units. Priorities included increasing clinical trial enrollment, fertility counseling, and creating environments attuned to AYA patients' social and psychological needs. Key barriers included limited funding, institutional resistance, and inadequate pediatric/adult team collaboration. Despite progress, the lack of standardized guidelines and long-term data on AYA unit efficacy remains a challenge. Further research is required to develop outcome metrics, refine care models, and enhance survival and quality of life for AYA cancer patients. [ABSTRACT FROM AUTHOR]

Rare cancers pose significant diagnostic challenges, leading to more tests and higher healthcare expenditures (HEs). Understanding the financial implications of diagnosing rare cancers is crucial, particularly in Canada, where overall HEs are high (12% of the GDP in 2023). We investigated the pre-diagnostic hospital–based HE for patients with malignant central nervous system (CNS) tumours and compared it to patients with common cancers across Canadian provinces, using in-patient and ambulatory care data (2010–2014) from the Canadian Institute for Health Information. Pre-diagnostic HE was calculated as the change in total HE (in-patient and out-patient) during the 12 months before diagnosis, calculated as the HE within this period minus the average annual HE estimated over the two preceding years. Comparison groups included pediatric patients diagnosed with leukemia and patients aged over 15 diagnosed with colorectal cancer and lung cancer. We used quantile regression to estimate the adjusted effect of diagnosis with a CNS tumour on pre-diagnostic HE. The results indicated that HE for CNS patients was higher compared to those with common cancers. The top three factors contributing to HE variation were encounter type (in-patient/out-patient), province (Alberta/Ontario), and comorbidities (yes/no). Further investigation is warranted to understand the drivers of the cost differences. [ABSTRACT FROM AUTHOR]

Episiotomy is a perineal incision enlarging the vaginal opening during labor, preventing severe perineal/vaginal/ano-rectal lacerations. We performed a systematic literature review (PRISMA guidelines; Pubmed, Scopus and Web of Science databases) of primary malignant tumors arising from the episiotomy site. Thirteen primary carcinomas were reported, mainly endometriosis-related histotypes (77%) (nine clear cell, CCC; one endometrioid, EC) with only two vulvar invasive squamous cell carcinomas and one adenoid cystic carcinoma of Bartholin's gland. No sarcomas, melanomas or malignant trophoblastic tumors were described. Endometriosis was associated with tumors or reported in history (62%). Malignant transformation occurred 3 to 27 (mean 16) years after diagnosis of endometriosis. Patients were usually post-/peri-menopausal (eight cases, 61%) (age range: 31–70 years, mean 50). Imaging should exclude distant (0% in our series) or lymph node metastases (three cases, 23%), looking for potential invasion of vagina (five cases, 39%), anus (including sphincter) (four cases, 31%) and/or other deep pelvic soft tissues (five cases, 39%). All patients underwent surgery, except for a CCC-patient (only chemoradiation) subsequently progressing and dying of disease. Adjuvant chemotherapy and/or radiotherapy were administered to five (39%) cases, neoadjuvant therapy to four cases (31%). Globally, three (23%) cases recurred or progressed, and two-thirds (15%) died of disease (1 CCC, 1 EC). Radical surgery with lymph node status evaluation and eventual excision should be performed when possible. Chemotherapy and/or radiotherapy can be considered in an adjuvant and/or neoadjuvant setting (or as only treatment in inoperable patients). However, the role of different treatments should be studied in further larger multicenter series. [ABSTRACT FROM AUTHOR]

(1) Background: Neoplasms of the central nervous system (CNS) encompass a cluster of malignant diseases originating from tissues or structures within the CNS. Environmental factors, including heavy metals, may contribute to their development. Therefore, this research was to investigate the association between heavy metal exposure and CNS tumor susceptibility using single and muti-metal models. (2) Methods: 63 CNS tumor patients and 71 controls were included. Urine samples from the CNS tumor patients and controls were analyzed for 47 metals using inductively coupled plasma-mass spectrometry in this study. Statistical analyses included conditional Wilcoxon rank-sum tests, logistic regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Bayesian Kernel Machine Regression (BKMR). (3) Results: In the single metal model, higher levels of seventeen metals might be associated with a lower incidence of CNS tumor, while higher exposure levels of five metals are associated with a higher incidence of tumor. LASSO regression selected nine metals for further BKMR analysis. The joint effects showed decreased tumor risk with increased metal mixture concentration. The level of the metals Ge, As, Rb, Zr, and Sn may be related to the incidence of meningiomas and gliomas. (4) Conclusions: This study explored the association between various metals and CNS tumors, providing ideas for future prospective cohort studies and laboratory studies, and providing a foundation for new ideas in the prevention and treatment of CNS tumors. [ABSTRACT FROM AUTHOR]

Purpose : We aim to investigate the clinical factors that affect the prognosis of overall survival (OS) for patients with high-grade parotid gland mucoepidermoid carcinoma (high-grade pMEC) and construct a nomogram for prognosis prediction. Subjects and method : Totally, 519 patients diagnosed as high-grade pMEC from the surveillance, epidemiology, and end results (SEER) database between 2004 and 2015 were reviewed. Independent prognostic factors for OS were identified by univariate and multivariate Cox regression analyses. Nomogram was generated to predict the individual's 3- and 5- year OS rates by using R software. Prediction ability was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) and model calibration was evaluated through calibration plots. Decision curve analysis (DCA) was used to assess the clinical usefulness and net benefit. Results : The results of univariate analysis demonstrated that age, AJCC stage, T stage, N stage, M stage, extraparenchymal lesions, regional lymph nodes status, lymph node dissection status, radiotherapy, chemotherapy, and surgery were significantly correlated with the OS (P < 0.05). Multivariate Cox regression analyses showed that older age at diagnosis, advanced AJCC stage, and positive regional lymph nodes were independent risk factors for OS. In addition, the present study revealed that radiotherapy and surgery were independent protective factors for OS (P < 0.05). The nomograms showed accurate prognostic ability that individually predict 3-years and 5-years overall survival (OS) rates based on age, AJCC stage, regional lymph nodes status, radiotherapy, and surgery. The area under the receiver operating characteristic (ROC) curve (AUC) of the nomogram used to predict the 3-year and 5-year overall survival rate were 0.779 and 0.793, indicating that the model had a good predictive power for the overall survival in high-grade pMEC patient. Conclusions : Using the SEER database, we performed univariate and multivariate analyses to determine independent prognostic factors in high-grade pMEC patients. Subsequently, we constructed and validated a prognostic nomogram to predict 3-and 5-year OS rates based on the SEER database and can assist clinicians to intuitively evaluate prognosis of high-grade pMEC patients. [ABSTRACT FROM AUTHOR]

This study aimed to explore contextual elements of the cancer experience that are consistently distressing and/or psychologically traumatic, as well as explore perceptions of Accelerated Resolution Therapy® (ART®) and its influence on the cancer experience. Using a qualitative descriptive design, semi-structured interviews were completed by 12 participants following the completion of ART. Interview data were analyzed using content analysis to identify major themes and patterns. Four themes included: (a) Cancer as the straw that broke the camel's back, (b) ART® is different from previous therapy, (c) Don't need to always be looking in the rearview mirror, and (d) Importance of early psychological intervention. Participants perceived that ART® was different and potentially more effective than other types of therapy they had previously received. Results support the diagnosis of cancer and the cumulative effects of previous life events and cancer-related stressors as traumatic events. [ABSTRACT FROM AUTHOR]

Background: Xerostomia is a common and difficult symptom experienced by patients with cancer. Pilocarpine is a cholinergic agent that stimulates salivation. Aim: To assess the feasibility of conducting a N-of-1 trial to determine the efficacy of pilocarpine orally dissolving tablets in patients with xerostomia. Design: Double-blind, crossover, placebo-controlled N-of-1 trials of 5 mg pilocarpine tablets vs placebo. Each trial consisted of three 6-day cycles containing pilocarpine (3 days) and placebo (3 days) in random order. Setting/participants: Participants with advanced cancer and xerostomia (scoring >3 on an 11-point numerical rating scale) from any cause, were recruited from an inpatient and outpatient palliative care unit in Brisbane, Australia. Results: Eighteen people were recruited in 17 months. Nine withdrew, seven before or during the first 4 days. Three withdrew due to unacceptable side effects. Two participants met the definition of response (⩾2 point reduction in mean scores active vs placebo cycles). When assessing individual cycles, 15 out of 27 cycles (56%) met the definition of response. More people reported at least one mild episode during pilocarpine than placebo of nausea (6 vs 3), vomiting (3 vs 0) and sweating (3 vs 2). About 48% of adverse event classifications were reported in placebo cycles only. Conclusion: Recruitment to an N-of-1 trial for xerostomia is feasible but attrition was high (50%). Early dropout may have been due to the trial length, complexity, appropriateness or number of questionnaires. Adverse events were generally mild. Two of 10 participants were considered to have benefited from pilocarpine warranting ongoing treatment. [ABSTRACT FROM AUTHOR]

Background: Many patients with advanced cancer are unaware of their limited prognosis, however little is known about the change in awareness during the last year of their lives. Aim: To investigate changes in the perception of prognosis in the last year of life of patients with advanced cancer and its associated factors. Design: Prospective, longitudinal, multicentre, observational study in patients with advanced cancer (eQuiPe). Patients completed 3-monthly follow-up questionnaires until death. Setting/participants: Adult patients diagnosed with advanced cancer were recruited by their treating physician or self-enrolled in one of the forty Dutch hospitals. Only deceased patients with available prognostic data were included for analysis (n = 801). Results: Perception of prognosis changes in the last year of life with an increase in the percentage of patients who are aware of their limited prognosis (from 15% to 40%). Especially in the last 6 months of life, most of the changes were towards a more realistic perception of prognosis. Patients who did not want to know their prognosis remained relatively stable in their wish not to know (range: 14%–18%). Time to death was associated with having a perception of prognosis of < 1 year, >1 year or not knowing the prognosis, but was not associated with not wanting to know the prognosis. Conclusion: Becoming aware of their limited prognosis may make patients with advanced cancer more receptive to start end-of-life discussions. Although some patients prefer not to know their prognosis, it remains important to respectfully explore their preferences and wishes for end-of-life care. [ABSTRACT FROM AUTHOR]

The life experiences of children with cancer and their parents as individuals have been well documented in literature. However, little is known about their experiences as child–parent dyads in Pakistan regarding these children's quality of life. Thus, the study was conducted in the context of the family-centric society of Pakistan. In-depth interviews were conducted with 28 participants (14 child–parent dyads), comprising 9 female and 5 male children receiving cancer treatment and 8 mothers and 6 fathers (primary caregivers). All the participants were Muslims and hailed from diverse ethnic backgrounds, and most belonged to middle socioeconomic backgrounds. Thematic analysis was performed using Braun and Clarke's (2006) framework, which revealed four themes: (1) Stress, Fears, and Optimism; (2) Reactions to Restrictions; (3) Adaptation and Coping; and (4) Support Structure and Mechanisms. The findings indicated that children's and parents' daily lives were affected in various ways during the children's cancer journey. They faced several challenges which impacted their well-being. Particularly, the children considered their symptoms as restrictions in the way of carrying out their routine lives. However, children and parents also elaborated on using different coping strategies, such as play, reminiscing the past, incorporating religious practices into their daily routines, and keeping a family-centred approach towards the child's care. The parents also recommended that cancer-specialised services and support groups should be accessible. Conclusively, these findings are useful for healthcare providers in giving family-centred care to afflicted families and devising innovative interventions that address the needs of children with cancer and improve their quality of life. [ABSTRACT FROM AUTHOR]

Fear of cancer recurrence is the most prevalent and burdensome emotional concern among cancer survivors' spouses after treatment. This qualitative study aimed to reveal death-related experiences of spouses of cancer survivors in remission, in the context of fear of cancer recurrence. Seven spouses (aged 35–56), four women and three men were explored. Data were obtained using an unstructured interview and analyzed by inductive thematic analysis. The spouses associate cancer relapse with death, risk of losing their spouse. The threat of death triggers not only the feelings of insecurity, uncertainty about the future and loss of control, but also appreciation of life, focus on positive aspects in relationships. Planning for the "worst" scenarios and avoidance helped spouses to reduce tension and enhance control. Interventions for spouses should focus on promotion of emotional expression of death related concerns underlying fear of relapse, also developing new coping strategies to accept and tolerate uncertainty. [ABSTRACT FROM AUTHOR]

Simple Summary: The relationships between the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in immunotherapy are complex and nuanced, with significant implications for drug development, clinical trials, and regulatory decisions. While ORR remains a relevant metric, this analysis emphasizes that it should not be viewed as a standalone predictor of survival outcomes, particularly beyond first-line treatment and above certain ORR thresholds. To accurately predict patient outcomes and personalize therapy, clinicians should consider factors beyond ORR such as tumor biology, patient characteristics, treatment line and key survival metrics, including PFS and OS. This understanding underscores the need for a more comprehensive approach to oncology, potentially driving the development of more sophisticated biomarkers to guide immunotherapy decisions that optimize both response and survival outcomes, enhancing the efficacy and precision of cancer treatments. Understanding the relationship between the Objective Response Rate (ORR) and survival outcomes, notably Progression-Free Survival (PFS) and Overall Survival (OS), is relevant for assessing the efficacy of regimens in oncology. We evaluate the relationship between ORR, PFS and OS in immuno-oncology (IO) trials. Data from 68 clinical trials submitted to the FDA were evaluated, examining immunotherapy regimens, notably immune checkpoint inhibitors such as anti-programmed death (ligand)-1 [anti-PD-(L)1], cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitors and combination therapies [e.g., IO + IO, anti-PD-L1 + chemotherapy, anti-PD-L1 + CTLA-4, anti-PD-L1 + TKI (tyrosine kinase inhibitors)]. Studies were included based on their reporting of ORR, PFS, and OS. Of the 68 clinical trials reviewed, 55 were included in the analysis. The correlation between ORR and PFS was moderate across most immunotherapy regimens, indicating that ORR can serve as a useful predictor of short-term disease control. However, the correlation between ORR and OS was weaker, especially in trials including combination therapies, indicating that ORR alone may not reliably predict long-term survival outcomes. ORR predicts PFS better in first-line treatment but declines in later lines and remains a weak OS predictor overall. Differing degrees of correlation between ORR and survival metrics, particularly across treatment lines and combinations, are observed. While ORR can serve as a surrogate marker for PFS in IO trials, its utility in predicting OS is restricted and the interpretation of the relationship between ORR and PFS or OS is a key limitation. Rather, a decline in PFS with increasing ORR may reflect trial differences rather than a direct relationship. Future analyses should adopt better methodologies to capture these dynamics and focus on improving surrogate endpoints for immunotherapy to improve clinical trial design and patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: SGLT2 inhibitors, first introduced in the clinical practice for diabetes, have been suggested to be effective against different types of cancer. Here, we review the literature on the re-purposing of SGLT2 inhibitors for cancer, focusing on the data that are most relevant for human cancer. Cancer cells utilize larger amounts of glucose than their normal counterparts, and the expression of GLUT transporters is a known diagnostic target and a prognostic factor for many cancers. Recent evidence has shown that sodium-glucose transporters are also expressed in different types of cancer, and SGLT2 has raised particular interest because of the current availability of anti-diabetic drugs that block SGLT2 in the kidney, which could be readily re-purposed for the treatment of cancer. The aim of this article is to perform a narrative review of the existing literature and a critical appraisal of the evidence for a role of SGLT2 inhibitors for the treatment and prevention of cancer. SGLT2 inhibitors block Na-dependent glucose uptake in the proximal kidney tubules, leading to glycosuria and the improvement of blood glucose levels and insulin sensitivity in diabetic patients. They also have a series of systemic effects, including reduced blood pressure, weight loss, and reduced inflammation, which also make them effective for heart failure and kidney disease. Epidemiological evidence in diabetic patients suggests that individuals treated with SGLT2 inhibitors may have a lower incidence and better outcomes of cancer. These studies are confirmed by pre-clinical evidence of an effect of SGLT2 inhibitors against cancer in xenograft and genetically engineered models, as well as by in vitro mechanistic studies. The action of SGLT2 inhibitors in cancer can be mediated by the direct inhibition of glucose uptake in cancer cells, as well as by systemic effects. In conclusion, there is evidence suggesting a potential role of SGLT2 inhibitors against different types of cancer. The most convincing evidence exists for lung and breast adenocarcinomas, hepatocellular carcinoma, and pancreatic cancer. Several ongoing clinical trials will provide more information on the efficacy of SGLT2 inhibitors against cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides an overview of relevant outcomes of AYAs with cancer in order to develop a core outcome set (COS: an agreed standardized collection of outcomes) for this population. A literature search was conducted, after which articles were reviewed by two independent researchers using Rayyan to screen articles by their title/abstract and their full text. The data were extracted using a tailored extraction framework by a team of reviewers. A total of 1631 of the 17,301 screened articles were included. Of the five core areas, functioning (47.0%) and epidemiology (44.9%) were covered most often, followed by physiological/clinical (42.4%), resource use (6.1%), and adverse events (4.5%). The most represented outcome domains include mortality/survival, delivery of care, outcomes relating to neoplasms, and emotional functioning/well-being. This literature review provides a foundation for the development of an AYA-specific COS to improve the relevance and efficiency of measuring outcomes, the pooling of (international) data, and the value of care for AYAs with cancer. Background: In adolescents and young adults (AYAs) with cancer, the importance of patient-centered research outcomes is increasingly acknowledged and there is a need for consensus on the most relevant outcomes. This review provides a comprehensive overview of outcomes relevant to AYAs with cancer in order to develop an AYA-specific core outcome set (COS) as part of the European project STRONG-AYA. Methods: A literature search was conducted to identify relevant articles in five databases. Each article was reviewed by two independent researchers, using Rayyan (an online tool) to screen articles by their title/abstract and then by their full text. Subsequently, the data were extracted using a predefined, tailored extraction framework. Results: In total, 17,301 articles were screened, of which 1631 were included in the analyses. Registry studies (52.9%) were the most used study type. Well-represented continents were North America (50.3%) and Europe (27.8%). Of the five core areas, functioning (47.0%) and epidemiology (44.9%) were covered most often, followed by physiological/clinical (42.4%), resource use (6.1%), and adverse events (4.5%). The outcome domains that were represented the most include mortality/survival (43.1%), delivery of care (23.4%), outcomes relating to neoplasms (22.7%), and emotional functioning/well-being (19.2%). Conclusions: This literature review provides a foundation for the development of an AYA-specific COS for improving the relevance and efficiency of measuring outcomes, the pooling of (international) research data, and the value of care for current and future AYAs with cancer. Finalization and refinement of the COS should be a priority for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is characterized by variability at several levels. Individual cells within a tumor exhibit genetic and non-genetic differences, tumors within a patient exhibit different characteristics, and patients themselves have different responses to therapeutics and clinical outcomes. The heterogeneous nature of cancer complicates the ability to predict patient outcomes and the delivery of curative treatment. The present study explores the ways in which the molecular heterogeneity of cancer impacts clinical outcomes, with a unique focus on how emerging technologies may be leveraged to improve patient care. Cancer heterogeneity is a major challenge in oncology, complicating diagnosis, prognostication, and treatment. The clinical heterogeneity of cancer, which leads to differential treatment outcomes between patients with histopathologically similar cancers, is attributable to molecular diversity manifesting through genetic, epigenetic, transcriptomic, microenvironmental, and host biology differences. Heterogeneity is observed between patients, individual metastases, and within individual lesions. This review discusses clinical implications of heterogeneity, emphasizing need for personalized approaches to overcome challenges posed by cancer's diverse presentations. Understanding of emerging molecular diagnostic and analytical techniques can provide a view into the multidimensional complexity of cancer heterogeneity. With over 90% of cancer-related deaths associated with metastasis, we additionally explore the role heterogeneity plays in treatment resistance and recurrence of metastatic lesions. Molecular insights from next-generation sequencing, single-cell transcriptomics, liquid biopsy technology, and artificial intelligence will facilitate the development of combination therapy regimens that can potentially induce lasting and even curative treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Rare cancers are known to be a group that suffer from a lack of information and delays in diagnosis. Patients often have an impaired health-related quality of life (HRQoL), with their lives being affected socially, mentally, and physically because of their diagnosis and/or treatment. The aim of our research was to unravel the heterogeneity of HRQoL in patients with a solid rare cancer per EURACAN domain, and to summarize the HRQoL measures used in research. A total of 464 articles investigated HRQoL in this population. Different measurement approaches were taken per EURACAN domain. Overall, this review shows that HRQoL measurement is slowly entering the field of clinical rare cancer research. Future research should invest in creating adequate HRQoL measurement strategies and/or HRQoL tools for use in solid rare cancer research and care to optimize patient outcomes. Background: Health-related quality of life (HRQoL) is an important patient-reported outcome for all cancer patients, including adult patients with rare solid cancers. However, current knowledge of HRQoL in this population is limited, which hinders the delivery of personalized care. This review aimed to explore the heterogeneity of HRQoL among adult patients with a solid rare cancer across the ten European Reference Network for Rare Adult Solid Cancers (EURACAN) domains and to summarize the HRQoL measures used in clinical research. Methods: A systematic literature search was conducted to identify all clinical studies assessing HRQoL in adult patients with a solid rare cancer. Four databases (MEDLINE, PubMed, PsycINFO, and Web of Science/Scopus) were searched (February 2023). Results: The search yielded 18,704 articles, of which 1416 articles were fully screened and 463 were eligible for analysis. Of these, 397 studies used generic tools to assess HRQoL, while 270 used tumor-specific instruments. Three EURACAN domains (sarcoma, endocrine tumors, and thoracic tumors) primarily assessed HRQoL using generic questionnaires. Additionally, the rare gynecological tumor, rare male genitourinary, and sarcoma EURACAN domains lacked specific HRQoL measures. Brain, head and neck, and uveal melanoma EURACAN domains used tumor- or domain-specific questionnaires in more than half of the studies. Conclusions: This state-of-the-art literature review shows that HRQoL assessment is gradually becoming more prevalent in adult solid rare cancer research. A combination of generic, tumor-specific, and domain-specific questionnaires across various rare cancer domains has proven effective in capturing a broad range of HRQoL issues. However, many EURACAN domains still lack specific strategies for assessing HRQoL, which limits the ability to fully understand and address patients' experiences. Future research should prioritize developing comprehensive and robust HRQoL measurement strategies and tools to enable meaningful clinical research and to ensure that the patient voice is incorporated in their clinical care. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurate patient illness understanding is associated with improved end-of-life outcomes. In this study, we investigated assessment tools used to examine illness understanding in randomized clinical trials involving advanced cancer patients. We identified five categories of assessment measures: prognostic awareness, health status, curability, treatment intent, and treatment risks/benefits. Of the 27 articles included in our final sample, we found significant heterogeneity in the questions, answer choices, how accuracy was defined, and the accuracy rates in all categories except for health status. This review shows the high variability present among illness understanding assessments, providing insights to improve the conceptualization and standardization of these approaches. The best tools to assess patient illness understanding are unclear. Here, we examined the assessment tools for illness understanding administered in randomized clinical trials (RCTs) involving patients with advanced cancer, how accuracy of illness understanding was assessed, and each tool's level of accuracy. We conducted a systematic review of Ovid MEDLINE, Ovid EMBASE, and Web of Science from database inception to 28 February 2024. We included all RCTs that reported on illness understanding assessments in cancer patients. The assessment measures were classified into five categories: prognostic awareness, health status, curability, treatment intent, and treatment risks/benefits. We extracted the questions, answers, definitions of accuracy, and accuracy rates of each category. The final sample included 27 articles based on 16 RCTs; five articles (19%) had a Jadad score of ≥3. Among these articles, 10 (37%) assessed prognostic awareness, 4 (15%) assessed health status, 9 (33%) assessed curability, 11 (41%) assessed treatment intent, and 3 (11%) assessed treatment risks/benefits. Only four RCTs examined illness understanding as a primary outcome or communication intervention. We observed significant heterogeneity in the questions, answers, definition of accuracy, and accuracy rate of patients' responses for all themes except for health status. The accuracy rate ranged from 6% to 33% for prognostic awareness, 45% to 59% for health status, 35% to 84% for curability, 26% to 88% for treatment intent, and 17% to 75% for treatment risks/benefits. This study highlights significant variation in current illness understanding assessments and opportunities for standardization to support clinical practice and research. [ABSTRACT FROM AUTHOR]

Background: The population figures in Germany are obtained by updating the results of the latest census with information from the statistics on birth, deaths and migration statistics. The Census 2011 in Germany corrected population figures, which have only been updated over a long period of time. The aim of this work is to show the effect of the census-based correction of the population figures on the magnitude of mortality rates in Germany 2011–2013. Methods: We compared mortality rates (total, cancer, and cardiovascular disease) for the period 2011–2013 based on the uncorrected and Census 2011 corrected population figures. We also compared the effect of the choice of different standard populations in the age standardization of rates on the difference in uncorrected and corrected mortality rates. Results: There is a clear decline in age-specific cancer mortality among men aged 90 and over when using the uncorrected population figures, which is reversed as soon as the corrected population figures are used. Among women, there is hardly any difference between the uncorrected and corrected mortality rates. The correction of the population figures does not lead to a qualitatively different pattern in the mortality rates for cardiovascular diseases and myocardial infarction, but it increases the magnitude of the rates, particularly for elderly men. Standard populations with higher weights at older ages produced larger corrections in mortality rates. Conclusions: Even though the Census 2011 corrected nationwide mortality rates without age stratification differed only slightly from the uncorrected rates, there were noticeable increases in mortality, particularly in the city states of Hamburg and Berlin and in old age. Due to the particularly large error in the population figures in the older age range, an age standard that assigns lower weights at older ages should be used for age standardization of rates wherever possible. [ABSTRACT FROM AUTHOR]

Background: Genetic and genomic literacy is pivotal in empowering cancer patients and citizens to navigate the complexities of omics sciences, resolve misconceptions surrounding clinical research and genetic/genomic testing, and make informed decisions about their health. In a fast-evolving scenario where routine testing has become widespread in healthcare, this scoping review sought to pinpoint existing gaps in literacy and understanding among cancer patients and the general public regarding genetics and genomics. Methods: Adhering to the PRISMA framework, the review included 43 studies published between January 2018 and June 2024, which evaluated the understanding of genetics and genomics among cancer patients, caregivers, and citizens. Results: Although the selected studies had significant heterogeneity in populations and evaluation tools, our findings indicate inadequate literacy levels, with citizens displaying lower proficiency than cancer patients and caregivers. This review highlighted consistent knowledge gaps in understanding the genetic and genomic underpinnings of diseases, encompassing misconceptions about mutation types and inheritance patterns, limited awareness of available genetic testing options, and difficulties in interpreting test results. Ethical and privacy concerns and the psychological impact of genetic testing were also common, highlighting the imperative need for effective communication between healthcare providers and patients. Conclusions: Given the dynamic nature of genomic science, the review underscores the need for continuously evolving educational programs tailored to diverse populations. Our findings could guide the development of educational resources addressed explicitly to cancer patients, caregivers, and the lay public. [ABSTRACT FROM AUTHOR]

Simple Summary: This review examines the chronological timeline of studies identifying and characterizing calreticulin (CRT) from its origin as an endoplasmic reticulum (ER) protein to an important cell surface signaling molecule. A detailed literature analysis shows that CRT was initially discovered as the Ca2+-binding ER protein, called calregulin, and not as the SR protein(s), called the high-affinity calcium-binding protein (HACBP). We further elucidate the critical functions of CRT in calcium homeostasis, protein folding, immunogenic cell death (ICD), and antigen presentation. The roles of CRT in the regulation of the destruction of cancer cells by the immune system and as a causative factor in certain blood cancers are also discussed. Overall, this review critically and comprehensively identifies the original studies that revealed CRT's discovery, structure, and functions in the ER and at the cell surface. Calreticulin (CRT) is a 46 kDa highly conserved protein initially identified as calregulin, a prominent Ca2+-binding protein of the endoplasmic reticulum (ER). Subsequent studies have established that CRT functions in the ER's protein folding response and Ca2+ homeostatic mechanisms. An ER retention signal on the carboxyl terminus of CRT suggested that CRT was restricted to the ER. However, the identification of CRT in the nucleus and cytosol has established that CRT is a multi-compartmental, multifunctional protein. CRT also plays an important role in cancer progression. Most recently, CRT was identified on the cell surface and shown to be a potent 'eat-me' signal that plays a key role in the uptake of apoptotic and viable cancer cells by phagocytes. Elevated CRT exposure on the outer leaflet of cancer cells has been linked with anticancer immunity and superior therapeutic outcomes in patients with non-small cell lung carcinoma, colorectal carcinoma, acute myeloid leukemia, ovarian cancer, and high-grade serous carcinomas. Mutations in the CRT gene have been identified in a subset of patients with myeloproliferative neoplasms. The most recent studies from our laboratory have revealed a new and significant function for extracellular CRT as a plasminogen receptor. This discovery has profound implications for our understanding of the role of CRT in myeloproliferative neoplasms, specifically, essential thrombocythemia. [ABSTRACT FROM AUTHOR]

Simple Summary: Telomeres play an integral role in preventing genomic instability by protecting chromosomal ends using telomeric repeats, and their dysfunction may lead to premature aging disorders and age-related diseases. During cellular division, they undergo telomere attrition, resulting in the gradual shortening of those protective caps, leading to genomic instability and cellular aging. Critically short telomeres in normal cells trigger senescence, a major contributor to age-related diseases, and opens the door for genomic instability, which promotes carcinogenesis. This review aims to provide an updated overview of telomere biology and therapeutic strategies around telomere attrition. We emphasize the importance of understanding the complex balance between preserving telomere length in aging while inhibiting telomere maintenance in cancer by proposing Optimal Therapeutic Approaches based on the most updated literature. Background/Objectives: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer. The purpose of this review is to provide an updated overview of telomere biology and therapeutic tactics to address aging and cancer. Methods: We used the Rayyan platform to review the PubMed database and examined the ClinicalTrial.gov registry to gain insight into clinical trials and their results. Results: Cancer cells activate telomerase or utilize alternative lengthening of telomeres to escape telomere shortening, leading to near immortality. Contrarily, normal cells experience telomeric erosion, contributing to premature aging disorders, such as Werner syndrome and Hutchinson–Gilford Progeria, and (2) aging-related diseases, such as neurodegenerative and cardiovascular diseases. Conclusions: The literature presents several promising therapeutic approaches to potentially balance telomere maintenance in aging and shortening in cancer. This review highlights gaps in knowledge and points to the potential of these optimal interventions in preclinical and clinical studies to inform future research in cancer and aging. [ABSTRACT FROM AUTHOR]