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The worldwide population is ageing, alongside an increase in cancer incidence rates. Over the past 10 years, there has been huge progress in the field of oncology with earlier diagnosis and an expansion of treatment options, leading to a growing number of older people living with cancer. That has meant that caring for older patients with cancer is now part of day-to-day oncology practices. This cohort often has geriatric syndromes and a higher prevalence of frailty and complex needs and preparing our clinical services to optimise care for these patients is essential. Whilst it is widely accepted that comprehensive geriatric assessments are of benefit to patients, only a small proportion of patients can access these through specialised teams during their cancer care. In the past few years there has been significant progress in this field throughout the United Kingdom (UK). The goal of this review is to inform other health care systems how to learn from what has been done in the UK. This paper provides an update from our previous review in 2020, detailing the new services being implemented and made available to patients and an expansion in the number of new pilot teams and research projects/trials throughout the four nations of the UK., Competing Interests: Declaration of Competing Interest Mark Baxter reports a relationship with Servier Monde that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Mark Baxter reports a relationship with Ipsen that includes: speaking and lecture fees and travel reimbursement. Mark Baxter reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Mark Baxter reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: speaking and lecture fees. Kirsty Balachandran reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Anne Barrell reports a relationship with Roche that includes: travel reimbursement. Anne Barrell reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Anne Barrell reports a relationship with Novartis AG that includes: speaking and lecture fees. Nicolo Matteo Luca Battisti reports a relationship with Pfizer Inc. that includes: board membership, speaking and lecture fees, and travel reimbursement. Nicolo Matteo Luca Battisti reports a relationship with Abbott that includes: board membership. Nicolo Matteo Luca Battisti reports a relationship with Sanofi that includes: board membership and speaking and lecture fees. Nicolo Matteo Luca Battisti reports a relationship with Astellas Pharma Inc. that includes: board membership. Nicolo Matteo Luca Battisti reports a relationship with Exact Sciences Corporation that includes: travel reimbursement. Nicolo Matteo Luca Battisti reports a relationship with Eli Lilly and Company that includes: speaking and lecture fees and travel reimbursement. Nicolo Matteo Luca Battisti reports a relationship with AbbVie Inc. that includes: speaking and lecture fees. Nicolo Matteo Luca Battisti reports a relationship with Roche that includes: speaking and lecture fees. Nicolo Matteo Luca Battisti reports a relationship with Servier Monde that includes: speaking and lecture fees. Nicolo Matteo Luca Battisti reports a relationship with Gilead Sciences Inc. that includes: speaking and lecture fees. Nicolo Matteo Luca Battisti reports a relationship with AstraZeneca Pharmaceuticals LP that includes: speaking and lecture fees. Kwok-Leung Cheung reports a relationship with Roche that includes: consulting or advisory. Kwok-Leung Cheung reports a relationship with Cancers that includes: travel reimbursement. Helen Brown reports a relationship with Roche that includes: funding grants. Fabio Gomes reports a relationship with AstraZeneca Pharmaceuticals LP that includes: speaking and lecture fees and travel reimbursement. Fabio Gomes reports a relationship with Roche that includes: speaking and lecture fees and travel reimbursement. Fabio Gomes reports a relationship with Boehringer Ingelheim GmbH that includes: speaking and lecture fees and travel reimbursement. Fabio Gomes reports a relationship with Pfizer Inc. that includes: speaking and lecture fees and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cancer rehabilitation and exercise oncology (CR/EO) have documented benefits for people living with and beyond cancer. The authors examined proximity to CR/EO programs across the United States with respect to population density, race and ethnicity, socioeconomic status, and cancer incidence and mortality rates., Methods: This cross-sectional study was conducted in 2022-2023. Online searches were initiated to identify CR/EO programs. Geocoding was used to obtain latitudinal and longitudinal geospatial coordinates. Demographic data were abstracted from the 2020 5-year American Community Survey. Cancer incidence and mortality data were obtained from the Centers for Disease Control and Prevention. US 2013 Rural-Urban Continuum Code (RUCC) classification was used to define counties as either urban (RUCC 1-3) or rural (RUCC 4-9). Multivariable logistic regression was used to evaluate the association between being far from a program and census-tract level factors., Results: In total, 2133 CR/EO programs were identified nationwide. The distance from a program increased with decreasing population density: rural tracts were 17.68 ± 0.24 miles farther from a program compared with urban tracts (p < .001). Program proximity decreased as the neighborhood deprivation index increased (p < .001). Exercise oncology programs were less common than cancer rehabilitation programs in tracts with a larger proportion of minority residents (p < .001)., Conclusions: Prior research has documented that underrepresented populations have worse cancer-related symptoms and higher cancer mortality. Herein, the authors document their findings that these same populations are less likely to have proximity to CR/EO programs, which are associated with improved cancer-related symptoms and cancer mortality outcomes. To realize the positive outcomes from CR/EO programming, efforts must focus on supporting expanded programming and sustainable payment for these services., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Estimates suggest that one in two people will experience cancer in their lifetime. Cancer and the treatment of cancer can have several impacts on oral health. It is therefore important that dental teams are supported in managing this group of patients especially in primary care dental settings, where most of these patients will first present to dental services. The aim of this study was to explore current practice and beliefs about managing patients with, or who have had, cancer in primary dental care settings., Methods: Online focus groups consisting of dental professionals working in primary care dental settings in Scotland, were conducted. Areas explored included cancer types seen, perceived role, challenges, and areas where further support was desired. Data from focus group transcripts were analysed using thematic analysis., Results: Four focus groups were conducted with a total of fifteen participants. Themes identified related to the types of cancers seen in primary care dental settings; communication between dental and medical teams; patient experience; mixed healthcare messages; patient engagement with their healthcare; challenges in treatment planning; apprehension about what can safety managed in primary care; and wider system factors influencing the management of patients with, or who have had, cancer. Areas where support exists but further support is desired were also identified., Conclusions: Challenges appear to exist in the provision of oral healthcare for patients with, or who have had, cancer. This study has indicated several areas where further support could be targeted. The results should be validated by further research., Competing Interests: Declarations. Ethics approval and consent to participate: This work is categorised as service development; therefore, NHS Ethics or research and development approval was not required. This work was conducted in accordance with the UK Policy Framework for Health and Social Care Research (NHS Health Research Authority, 2023) and the 2020 edition of the Governance Arrangements for Research Ethics Committees (NHS Health Research Authority, 2020). All participants read a participant information sheet and consented to their involvement in the study by completing a digital consent form. Consent for publication: All participants read a participant information sheet and completed a digital consent form which confirmed agreement to anonymised quotations being used in publications and presentations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

It is widely regarded that the anti-tumour immune response drives clearance of tumours and leads to prolonged survival in patients. However, tumours are adept at reprogramming the surrounding microenvironment to an immunosuppressive milieu to prevent successful immune directed killing. Adhesion of cells to the extracellular matrix is essential for regulating cellular processes such as survival, proliferation and migration. This adhesion is largely conducted via integrins and their related intracellular signalling networks. Adhesion proteins such as focal adhesion kinase (FAK) are expressed in both tumour cells and cells of the surrounding microenvironment, and are often dysregulated in cancers. Recent work has demonstrated that adhesion proteins are contributing to regulation of the immunosuppressive microenvironment within tumours, and could provide a new avenue to target in combination with immunotherapies. Here, we provide an overview of the effort being made to elucidate the roles adhesion proteins play in modulating anti-tumour responses within a variety of cancer settings. In particular we focus on the multifaceted role of FAK within the tumour immune microenvironment. Finally, we summarise the data in clinical trials, where targeting FAK is being exploited to prime the tumour microenvironment and create potent responses when combined with immunotherapies., (© 2024 The Author(s).)

Background: Patients receiving chemotherapy require ongoing symptom monitoring and management to optimize their outcomes. In recent years, digital remote monitoring interventions have emerged to provide enhanced cancer care delivery experiences to patients and clinicians. However, patient and clinician experiential evaluations of these technologies are rare. Therefore, we explored user experiences and perceptions of one such intervention-Advanced Symptom Management System (ASyMS)-after its scaled deployment in the context of the Electronic Symptom Management System Remote Technology (eSMART) trial. The eSMART trial was a large, multicenter randomized controlled trial to evaluate the efficacy of ASyMS in 12 clinical sites in 5 European countries., Objective: In this qualitative study, both patients' and clinicians' experiences of using ASyMS for up to 6 cycles of chemotherapy were explored to understand the impact of ASyMS on patients' experiences, clinical practice, and supportive care delivery., Methods: For this analysis, individual, semistructured, one-to-one interviews with 29 patients with breast, colorectal, and hematological cancers and 18 clinicians from Austria, Greece, Ireland, Norway, and the United Kingdom were conducted. Interviews focused on patients' and clinicians' experiences of using ASyMS, care organization and changes in practice following the introduction of ASyMS, perceived changes in care associated with the use of ASyMS, and its potential for future integration into routine chemotherapy care pathways., Results: Thematic analysis identified several themes that describe patients' and clinicians' experiences using ASyMS. One central orienting theme-ASyMS as a facilitator of change-was supported by 5 key themes associated with human and technology monitoring: reassurance, enhanced communications and relationships, knowing what is "normal" and what is to be expected, enhancing cancer care experiences, and informing future cancer care., Conclusions: This study is the first to evaluate both patients' and clinicians' experiences of using a digital health intervention to remotely monitor chemotherapy symptoms across 5 countries. Experiences with ASyMS were positive from both patients' and clinicians' perspectives, although some improvements to support the wider-scale rollout and sustained implementation were identified. Overall, this study demonstrates that real-time remote monitoring systems can help patients feel more reassured during their chemotherapy treatments and can help clinicians provide the right care, at the right time, and in the right place., Trial Registration: ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2016-015016., (©Lisa McCann, Liane Lewis, Olubukola Oduntan, Jenny Harris, Andrew Darley, Geir V Berg, Simone Lubowitzki, Katy Cheevers, Morven Miller, Jo Armes, Emma Ream, Patricia Fox, Eileen Patricia Furlong, Alexander Gaiger, Grigorios Kotronoulas, Elisabeth Patiraki, Stylianos Katsaragakis, Paul McCrone, Christine Miaskowski, Antonella Cardone, Dawn Orr, Adrian Flowerday, Simon Skene, Margaret Moore, Nicosha De Souza, Peter Donnan, Roma Maguire. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.12.2024.)

Introduction: The COVID-19 pandemic disrupted normal pathways to cancer diagnosis, particularly for screening and non-acute symptomatic patients. While reductions in overall cancer diagnoses have been reported elsewhere, any differential effects on emergency presentations, which are associated with poorer outcomes, have not been described., Material and Methods: Cross-sectional descriptive study from 2015 to 2021, based on International Cancer Benchmarking Partnership methods, where emergency route to diagnosis is defined as presenting as an emergency admission in the 30 days prior to cancer incidence date. Acute hospital records and cancer registrations were individually linked. Includes all individuals with a new diagnosis of specific cancers on the national cancer registry., Results: All cancers included showed reductions in non-emergency diagnoses in 2020, with varying recovery in 2021. The largest reductions in non-emergency diagnoses of about a third were for colorectal and cervical cancers in 2020. Non-emergency diagnoses of prostate cancer remained lower but upper GI higher in 2021. Emergency routes to diagnosis were significantly higher in 2020 for breast, cervical, colorectal and upper GI cancers and were higher in 2021 for breast and cervical cancers. The absolute magnitude of reductions in non-emergency diagnoses was greater than any increases in emergency diagnoses., Conclusions: In 2020, there were large reductions in numbers of cancers diagnosed through non-emergency pathways in Scotland, while those diagnosed via emergency routes fell only for prostate cancer. Some effects persisted or emerged through 2021. It is likely that opportunities to diagnose cancers in a favourable, elective manner have been lost. Further work is needed to describe outcomes among these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Childhood cancer treatment in Africa has a dramatically increasing patient population resulting in greater rehabilitation needs. The International Society of Paediatric Oncology (SIOP) mapped childhood cancer services in Africa including access to physiotherapy. Irrespective of income classification, just over two-thirds of countries in Africa reported having access to physiotherapy services in paediatric oncology sites. There is a lack of knowledge about African childhood physiotherapy services. Research is needed to understand the rehabilitation needs of these children/adolescents and how to meet their needs in a globally equitable and sustainable way., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

γδT cells represent a group of immune cells that are understudied but whose utility has been recognized for cancer immunotherapy purposes. Recent studies have highlighted a critical role for these cells in tumor initiation, growth, and metastasis and revealed an increasingly complex biology of γδT cell subsets that is context and tissue specific. We discuss here how γδT cell subsets are regulated, their interaction with cancer and other immune cells, and the implications from these latest discoveries for people with cancer., Competing Interests: Declaration of interests The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The fusion of cutting-edge imaging technologies with radiation therapy (RT) has catalyzed transformative breakthroughs in cancer treatment in recent decades. It is critical for us to review our achievements and preview into the next phase for future synergy between imaging and RT. This paper serves as a review and preview for fostering collaboration between these two domains in the forthcoming decade. Firstly, it delineates ten prospective directions ranging from technological innovations to leveraging imaging data in RT planning, execution, and preclinical research. Secondly, it presents major directions for infrastructure and team development in facilitating interdisciplinary synergy and clinical translation. We envision a future where seamless integration of imaging technologies into RT will not only meet the demands of RT but also unlock novel functionalities, enhancing accuracy, efficiency, safety, and ultimately, the standard of care for patients worldwide., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant 'persister' (DTP) cells, have a prominent role in drug resistance. Although long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the past two decades, yet several aspects of their biology remain enigmatic. Here, we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumour. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumour microenvironment, including their potential to evade immune surveillance, remain to be discovered. Finally, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavours in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication., (© 2024. Springer Nature Limited.)

The ability to visualise cancer with imaging has been crucial to the evolution of modern radiotherapy (RT) planning and delivery. And as evolving RT technologies deliver increasingly precise treatment, the importance of accurate identification and delineation of disease assumes ever greater significance. However, innovation in imaging technology has matched that seen with RT delivery platforms, and novel imaging techniques are a focus of much research activity. How these imaging modalities may alter and improve the diagnosis and staging of cancer is an important question, but already well served by the literature. What is less clear is how novel imaging techniques may influence and improve practical and technical aspects of RT planning and delivery. In this review, current gold standard approaches to integration of imaging, and potential future applications of bleeding-edge imaging technology into RT planning pathways are explored., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Extrachromosomal DNA (ecDNA) are circular regions of DNA that are found in many cancers. They are an important means of oncogene amplification, and correlate with treatment resistance and poor prognosis. Consequently, there is great interest in exploring and targeting ecDNA vulnerabilities as potential new therapeutic targets for cancer treatment. However, the biological significance of ecDNA and their associated regulatory control remains unclear. Light microscopy has been a central tool in the identification and characterisation of ecDNA. In this review we describe the different cellular models available to study ecDNA, and the imaging tools used to characterise ecDNA and their regulation. The insights gained from quantitative imaging are discussed in comparison with genome sequencing and computational approaches. We suggest that there is a crucial need for ongoing innovation using imaging if we are to achieve a full understanding of the dynamic regulation and organisation of ecDNA and their role in tumourigenesis., (© 2024. The Author(s).)

Objectives: Advanced practice nursing roles in cancer care are diverse and exist across the cancer care continuum. However, the titles used and the scope of practice differ across countries. This diversity is likely to be misleading to patients and influence nurses' contribution to health care. An understanding of the current state of advanced practice nursing roles in cancer care internationally is needed to inform opportunities for future role development and enhance cancer nursing career pathways., Methods: This scoping review included a systematic search of four databases: MEDLINE, CINAHL, PsycINFO, and Academic Search Complete. Independent screening for papers meeting the review's inclusion criteria was undertaken using online screening software. Data extraction, coding, and mapping were undertaken in NVivo 12., Results: Of the 13,409 records identified, 108 met the review's inclusion criteria. A variety of roles in cancer care settings were described. The United States and the United Kingdom had the most titles for advanced practice nursing roles. Tumor-specific roles were described and integrated into different phases of the cancer care continuum. Trends in continuing professional development for advanced practice nurses in cancer care included the rise in Fellowship programs in the United States and practice-based education in the United Kingdom., Conclusions: The differences in advanced practice nursing roles in cancer care allow regional and institutional variation to meet the needs of patient populations and health care system demands. However, a lack of clarity surrounding titles and roles results in confusion and underutilization of these nurses' highly specialized skill sets., Implications for Nursing Practice: Incongruence in titles and scope of practice internationally will ultimately result in a merging of roles. There is a need for international agreement on education requirements for advanced practice nursing roles to promote career pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Advanced practice nursing in cancer care is a research priority of the European Oncology Nursing Society (EONS). Five authors are members of the EONS research working group (Maura Dowling, Eva Pape, Paz Fernández-Ortega, Cherith Semple, Amanda Drury). Maura Dowling, Eva Paper, and Denise Bryant-Lukosius were Guest Editors for the “Advanced Oncology Nursing Roles” Special issue of Seminars in Oncology Nursing. As authors of this article, they did not participate in any editorial process or decision-making, which was handled by another editor., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The last decade has seen rapid progress in the use of genomic tests, including gene panels, whole-exome sequencing, and whole-genome sequencing, in research and clinical cancer care. These advances have created expansive opportunities to characterize the molecular attributes of cancer, revealing a subset of cancer-associated aberrations called driver mutations. The identification of these driver mutations can unearth vulnerabilities of cancer cells to targeted therapeutics, which has led to the development and approval of novel diagnostics and personalized interventions in various malignancies. The applications of this modern approach, often referred to as precision oncology or precision cancer medicine, are already becoming a staple in cancer care and will expand exponentially over the coming years. Although genomic tests can lead to better outcomes by informing cancer risk, prognosis, and therapeutic selection, they remain underutilized in routine cancer care. A contributing factor is a lack of understanding of their clinical utility and the difficulty of results interpretation by the broad oncology community. Practical guidelines on how to interpret and integrate genomic information in the clinical setting, addressed to clinicians without expertise in cancer genomics, are currently limited. Building upon the genomic foundations of cancer and the concept of precision oncology, the authors have developed practical guidance to aid the interpretation of genomic test results that help inform clinical decision making for patients with cancer. They also discuss the challenges that prevent the wider implementation of precision oncology., (© 2024 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Mitochondrial metabolism and electron transport chain (ETC) function are essential for tumour proliferation and metastasis. However, the impact of ETC function on cancer immunogenicity is not well understood. In a recent study, Mangalhara et al. found that inhibition of complex II leads to enhanced tumour immunogenicity, T-cell-mediated cytotoxicity and inhibition of tumour growth. Surprisingly, this antitumour effect is mediated by succinate accumulation affecting histone methylation. Histone methylation promotes the transcriptional upregulation of major histocompatibility complex-antigen processing and presentation (MHC-APP) genes in a manner independent of interferon signalling. Modulating mitochondrial electron flow to enhance tumour immunogenicity provides an exciting new therapeutic avenue and may be particularly attractive for tumours with reduced expression of MHC-APP genes or dampened interferon signalling., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I 2  = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I 2  = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I 2  = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I 2  = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Introduction: Preventative spend is a global health and social care strategy. Improving Cancer Journeys (ICJ) is a proactive, holistic, multidisciplinary project consistent with this agenda, currently being rolled out across Scotland and parts of UK. ICJ helps people with cancer access whatever support they need to mitigate their most pressing concerns. This study hypothesised that ICJ service users should subsequently use less unscheduled care than matched cohorts not using ICJ., Methods: Retrospective observational cohort study using linked national datasets. N = 1,214 ICJ users in Glasgow were matched for age, sex, deprivation, cancer type, stage, and diagnosis year to two control groups: 1. Cancer patients from Glasgow before ICJ (pre-2014), 2. Cancer patients from rest of Scotland during study period (2014-2018). Cancer registrations were linked for 12-month baseline and study periods to: NHS24 calls, A&E admissions, inpatient hospital admissions, unscheduled care, number & cost of psychotropic prescriptions. Per-person mean service uses were compared between groups., Results: There was a significant increase in NHS24 calls in the ICJ group (0.36 per person vs. -0.03 or 0.35), more and longer A&E attendances in ICJ (0.37 per person vs. 0.19 or 0.26; 2.19 h per person vs. 0.81-0.92 h), more and longer hospital admissions in ICJ (4.25 vs. 2.59 or 2.53; 12.05 days vs. 8.37 or 8.64), more care pathways involving more steps in ICJ (0.77 spells vs. 0.39 or 0.57; 1.88 steps vs. 1.56 or 1.21), more psychotropic drug prescriptions and higher costs in ICJ (1.88 prescription vs. 1.56 or 1.21; £9.51 vs. £9.57 or £6.95) in comparison to both control groups., Discussion: ICJ users sourced significantly more unscheduled care than matched cohorts. These findings were consistent with much of the comparable literature examining the impact of non-health interventions on subsequent health spend. They also add to the growing evidence showing that ICJ reached its intended target, those with the greatest need. Together these findings raise the possibility that those choosing to use ICJ may also be self-identifying as a cohort of people more likely to use unscheduled care in future. This needs to be tested prospectively, because this understanding would be very helpful for health and social care planners in all countries where proactive holistic services exist., (© 2024. The Author(s).)

Stress hormones can contribute to cancer progression, but how immune cells play a role in this process is unclear. In a recent study in Cancer Cell, He et al. showed that glucocorticoids potentiate metastasis by skewing neutrophils toward pro-tumorigenic functions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: 5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU., Patients and Methods: NUC-3373 was administered as monotherapy to patients with advanced solid tumors refractory to standard therapy via intravenous infusion either on Days 1, 8, 15 and 22 (Part 1) or on Days 1 and 15 (Part 2) of 28-day cycles until disease progression or unacceptable toxicity. Primary objectives were maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) and schedule of NUC-3373. Secondary objectives included pharmacokinetics (PK), and anti-tumor activity., Results: Fifty-nine patients received weekly NUC-3373 in 9 cohorts in Part 1 (n = 43) and 3 alternate-weekly dosing cohorts in Part 2 (n = 16). They had received a median of 3 prior lines of treatment (range: 0-11) and 74% were exposed to prior fluoropyrimidines. Four experienced dose-limiting toxicities: two Grade (G) 3 transaminitis; one G2 headache; and one G3 transient hypotension. Commonest treatment-related G3 adverse event of raised transaminases occurred in < 10% of patients. NUC-3373 showed a favorable PK profile, with dose-proportionality and a prolonged half-life compared to 5-FU. A best overall response of stable disease was observed, with prolonged progression-free survival., Conclusion: NUC-3373 was well-tolerated in a heavily pre-treated solid tumor patient population, including those who had relapsed on prior 5-FU. The MTD and RP2D was defined as 2500 mg/m 2 NUC-3373 weekly. NUC-3373 is currently in combination treatment studies., Trial Registration: Clinicaltrials.gov registry number NCT02723240. Trial registered on 8th December 2015. https://clinicaltrials.gov/study/NCT02723240 ., (© 2024. The Author(s).)

Immunotherapy is heralded as the 'fifth pillar' of cancer therapy, after surgery, radiotherapy, chemotherapy and genomic medicine. It involves 'harnessing' patients' own immune system T-cells to treat cancer. In this article, I draw on qualitative interviews with practitioners working in oncology and patients in the UK, to trace metaphorical and discursive framing around immunotherapy. Immunotherapy aims to restore the functioning of the immune system to detect cancer (non-self), working with the self/non-self model that pervades immunology discourse more widely. Practitioners draw on metaphors that cement this self/non-self model, and that tend to depict the relationship between cancer and the immune system as an internal battle. Yet the discursive framing around immunotherapy also involves shifts that emphasize the body's own capacity to heal, where it is framed as 'gentle' or 'tolerable' on the body. Through this discursive shift, immunotherapy refigures the antagonism associated with the self/non-self model in the context of cancer. Analysing patients' embodied experiences of treatment, this article attends to the material realities and tensions provoked by this shift in discursive framing. This article contributes to feminist STS analyses of immunology discourse, and extends this literature by arguing that it is critical to address the material stakes of these discursive shifts by paying attention to patients' day-to-day experiences of treatment. The discursive framing of immunotherapy brings into being new forms of embodied patienthood in the context of cancer.

Objective: To examine and interpret trends in UK cancer incidence and mortality for all cancers combined and for the most common cancer sites in adults aged 35-69 years., Design: Retrospective secondary data analysis., Data Sources: Cancer registration data, cancer mortality and national population data from the Office for National Statistics, Public Health Wales, Public Health Scotland, Northern Ireland Cancer Registry, NHS England, and the General Register Office for Northern Ireland., Setting: 23 cancer sites were included in the analysis in the UK., Participants: Men and women aged 35-69 years diagnosed with or who died from cancer between 1993 to 2018., Main Outcome Measures: Change in cancer incidence and mortality age standardised rates over time., Results: The number of cancer cases in this age range rose by 57% for men (from 55 014 cases registered in 1993 to 86 297 in 2018) and by 48% for women (60 187 to 88 970) with age standardised rates showing average annual increases of 0.8% in both sexes. The increase in incidence was predominantly driven by increases in prostate (male) and breast (female) cancers. Without these two sites, all cancer trends in age standardised incidence rates were relatively stable. Trends for a small number of less common cancers showed concerning increases in incidence rates, for example, in melanoma skin, liver, oral, and kidney cancers. The number of cancer deaths decreased over the 25 year period, by 20% in men (from 32 878 to 26 322) and 17% in women (28 516 to 23 719); age standardised mortality rates reduced for all cancers combined by 37% in men (-2.0% per year) and 33% in women (-1.6% per year). The largest decreases in mortality were noted for stomach, mesothelioma, and bladder cancers in men and stomach and cervical cancers and non-Hodgkin lymphoma in women. Most incidence and mortality changes were statistically significant even when the size of change was relatively small., Conclusions: Cancer mortality had a substantial reduction during the past 25 years in both men and women aged 35-69 years. This decline is likely a reflection of the successes in cancer prevention (eg, smoking prevention policies and cessation programmes), earlier detection (eg, screening programmes) and improved diagnostic tests, and more effective treatment. By contrast, increased prevalence of non-smoking risk factors are the likely cause of the observed increased incidence for a small number of specific cancers. This analysis also provides a benchmark for the following decade, which will include the impact of covid-19 on cancer incidence and outcomes., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we showed that CAFs with a myofibroblast phenotype released extracellular vesicles that transferred proteins to endothelial cells (ECs) that affected their interaction with immune cells. Mass spectrometry-based proteomics identified proteins transferred from CAFs to ECs, which included plasma membrane receptors. Using THY1 as an example of a transferred plasma membrane-bound protein, we showed that CAF-derived proteins increased the adhesion of a monocyte cell line to ECs. CAFs produced high amounts of matrix-bound EVs, which were the primary vehicles of protein transfer. Hence, our work paves the way for future studies that investigate how CAF-derived matrix-bound EVs influence tumor pathology by regulating the function of neighboring cancer, stromal, and immune cells.

Background: Cancer survivors account for 15% to 20% of all intensive care unit (ICU) admissions. In general ICU populations, patients are known to experience reduced health-related quality of life (HRQoL). However, little is known about HRQoL impacts among cancer survivors following a critical illness in ICU., Objective: The aim of this study was to critically synthesize the evidence to further understand the impact of a critical illness and ICU admission in cancer survivors., Methods: An integrative review was conducted and reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines. Three electronic databases were searched (MEDLINE, CINAHL, and EMBASE) using keywords and Boolean logic. Quality appraisal, data extraction, and a narrative synthesis were completed for all included studies by 2 reviewers., Results: Eleven publications met inclusion criteria. Health-related quality-of-life domains most frequently reported in cancer survivors after discharge from ICU included the following: physical function limitations, physical symptoms, and anxiety/depression., Conclusions: Health-related quality of life decreased immediately after the admission to ICU with a gradual increase in the 3 to 12 months following. Cancer survivors are vulnerable to physical limitations, pain, and social isolation after an admission to ICU., Implications for Practice: Cancer survivors who have been affected by a critical illness are at risk of reduced HRQoL after an admission to ICU. This integrative review will help clinicians and researchers to develop patient-centered models of care during the recovery of critical illness, which are currently lacking in service delivery., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy., Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications., Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care., Setting: Nineteen UK oncology centres., Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 10 9 /l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded., Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion., Main Outcome Measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death., Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant., Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies., Trial Registration: This trial is registered as ISRCTN84288963., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment ; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Background: For hematology cancer patients, the process of dying is described as "troublesome." Qualitative studies have focused on views of healthcare professionals and caregiver stakeholders. To date, there have been no studies from the patient's perspective on facing death while in the last year of life., Objective: The aim of this study was to develop an understanding of the hematology cancer patient's experience of the process of dying in the last year of life., Methods: The study method was constructivist grounded theory using semistructured interviews, a constant comparison technique, and memoing to collection and analysis of data. The 21 participants were attending a UK cancer center, a cancer unit, or a hospice., Results: This article describes 1 core category within the incurable hematology cancer illness trajectory through 4 subcategories: transitional phase, chronic phase, dying phase, and liminal phase., Conclusion: This unique study illustrates that, although life can be prolonged, "facing death" still occurs upon hospitalization and relapse regularly over the illness trajectory., Implications for Practice: It is important that clinical practice acknowledges those participants in an incurable illness trajectory while living are focused on avoiding death rather than the ability to cure the disease. Services need to be responsive to the ambiguity of both living and dying by providing holistic management simultaneously, especially after critical episodes of care, to enhance the process of care in the last year of life, and assessment should incorporate the discussion of experiencing life-threatening events., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs., (© 2024. The Author(s).)

Background: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience., Methods: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival., Discussion: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone., Trial Registration: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023., (© 2024. The Author(s).)

Photodynamic therapy (PDT) is a specific cancer treatment with minimal side effects. However, it remains challenging to apply PDT clinically, partially due to the difficulty of translating research findings to clinical settings as the conventional 2D cell models used for in vitro research are accepted as less physiologically relevant to a solid tumour. 3D spheroids offer a better model for testing PDT mechanisms and efficacy, particularly on photosensitizer uptake, cellular and subcellular distribution and interaction with cellular oxygen consumption. 3D spheroids are usually generated by scaffold-free and scaffold-based methods and are accepted as physiologically relevant models for PDT anticancer research. Scaffold-free methods offer researchers advantages including high efficiency, reproducible, and controlled microenvironment. While the scaffold-based methods offer an extracellular matrix-like 3D scaffold with the necessary architecture and chemical mediators to support the spheroid formation, the natural scaffold used may limit its usage because of low reproducibility due to patch-to-patch variation. Many studies show that the 3D spheroids do offer advantages to gynceologcial cancer PDT investigation. This article will provide a review of the applications of 3D spheroid culture models for the PDT research of gynaecological cancers., Competing Interests: Declaration of competing interest This is to declare that the authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

In this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation (p < 0.013) in a dose-dependent manner across a panel of human cancer cell lines expressing ANXA1. The anti-proliferative effect of MDX-124 is instigated by arresting cell cycle progression with cancer cells accumulating in the G 1 phase of the cell cycle. Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1., (© 2024. The Author(s).)

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost-effective healthcare., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Objectives: Patients undergoing long-term anticancer therapy typically require one of 3 venous access devices: Hickman-type device (HICK), peripherally inserted central catheter (PICC), or implantable chest wall port (PORT). Recent evidence has shown PORT is safer and improves patient satisfaction. However, PORT did not show improvement in quality-adjusted life-years and was more expensive. Decisions regarding cost-effectiveness in the United Kingdom are typically informed by a cost-per-quality-adjusted life-year metric. However, this approach is limited in its ability to capture the full range of relevant outcomes, especially in the context of medical devices. This study assessed the potential cost-effectiveness of HICK, PICC, and PORT in routine clinical practice., Methods: This is a cost-consequence analysis to determine the trade-offs between the following outcomes: complication, infection, noninfection, chemotherapy interruption, unplanned device removals, health utilities, device insertion cost, follow-up cost, and total cost, using data from the Cancer and Venous Access clinical trial. We conducted value of implementation analysis of a PORT service., Results: PORT was superior in terms of overall complication rate compared with both HICK (incidence rate ratio 0.422; 95% CI 0.286-0.622) and PICC (incidence rate ratio 0.295; 95% CI 0.189-0.458) and less likely to lead to an unplanned device removal. There was no difference in chemotherapy interruption or health utilities. Total cost with device in situ was lower on PORT than HICK (-£98.86; 95% CI -189.20 to -8.53) and comparable with PICC -£48.57 (95% CI -164.99 to 67.86). Value of implementation analysis found that PORT was likely to be considered cost-effective within the National Health Service., Conclusion: Decision makers should consider including PORT within the suite of venous access devices available within in the National Health Service., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To describe the signalment, clinical findings, presumptive or definitive diagnosis, and outcome in cats with central cord syndrome (CCS)., Animals: 22 cats., Clinical Presentation: Cats evaluated for CCS at 7 referral hospitals between 2017 and 2021 were included. Information retrieved from medical records included signalment, physical and neurological examination findings, diagnostic investigations, definitive or presumptive diagnosis, treatment, and follow-up., Results: Median age at presentation was 9 years. Two neuroanatomical localizations were associated with CCS: C1-C5 spinal cord segments in 17 (77.3%) cats and C6-T2 spinal cord segments in 5 (22.7%) cats. Neuroanatomical localization did not correlate with lesion location on MRI in 8 (36.3%) cats. The most common lesion location within the vertebral column was over the C2 and C4 vertebral bodies in 6 (27.2%) and 5 (22.7%) cats, respectively. Peracute clinical signs were observed in 11 (50%) cats, acute in 1 (4.5%), subacute in 4 (18%), and chronic and progressive signs were seen in 6 (40.9%) cats. The most common peracute condition was ischemic myelopathy in 8 (36.3%) cats, whereas neoplasia was the most frequently identified chronic etiology occurring in 5 (22.7%) cats. Outcome was poor in 13 (59%) cats, consisting of 4 of 11 (36.6%) of the peracute cases, 3 of 4 (75%) of the subacute cases, and 6 of 6 of the chronic cases., Clinical Relevance: Central cord syndrome can occur in cats with lesions in the C1-C5 and C6-T2 spinal cord segments. Multiple etiologies can cause CCS, most commonly, ischemic myelopathy and neoplasia. Prognosis depends on the etiology and onset of clinical signs.

Objective: To critically synthesize and describe the use and methods of ecological momentary assessment (EMA) in cancer research., Data Sources: A systematic review was conducted and has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Guideline. Electronic databases (APA PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, and Web of Science Core Collection) were searched using a variety of keywords and subject headings by an expert systematic review librarian. All publications were double screened by two reviewers using predetermined exclusion and inclusion criteria throughout the full review process. The review used Covidence Systematic Review Software. Methodological quality assessment and data extraction were performed. A narrative synthesis was conducted to examine the aim for EMA, the characteristics of the study samples, the EMA sampling procedures, EMA completion rates, outcome measures, and any implications of findings for survivorship care., Conclusion: A total of 42 EMA studies in cancer were included. Most studies used an electronic mobile device to capture EMA data apart from several that used paper diaries. Existing studies were found to have significant heterogeneity in methods and widely varying approaches to design and self-report measurements. While EMA in cancer research holds significant promise to advance cancer care research into the future by increasing ecological validity and reducing retrospective bias and can capture the unique idiographic within-person change over time, in real-time, further research is needed to develop standardized EMA self-report questionnaires., Implications for Nursing Practice: This is the first comprehensive systematic review to describe the use and methods of EMA in cancer research. There is significant heterogeneity in methods and widely varying approaches to design and self-report measurements in EMA cancer research. People affected by cancer found taking part in EMA studies reported benefit from the experience. However, researchers must engage with cancer survivors in the development and co-design of future EMA questionnaires to ensure relevant and acceptability of EMA data collection protocols., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the experiences of people diagnosed with cancer during the COVID-19 pandemic., Data Sources: Qualitative data were collected through semistructured interviews conducted with people affected by cancer in the Australian context. Following institutional ethical approval, interviews were conducted over Microsoft Teams and Zoom platforms and complied with confidentiality requirements. Data were transcribed verbatim and analyzed, and emergent themes were developed using thematic analysis to understand patient experiences of cancer care during the COVID-19 pandemic., Conclusions: The COVID-19 pandemic was disruptive to the daily experiences of supportive care. Four overarching themes were identified related to: 1) the impact on accessing healthcare services, 2) encounters with healthcare professionals, 3) the impact on daily living, and 4) the impact of COVID on psychological well-being., Implications for Nursing Practice: As the COVID-19 pandemic held global consequences on cancer practices, it is recommended that nursing and other multidisciplinary healthcare professionals reflect upon these findings, in the context of planning for future pandemics. We encourage further exploration into the sustainability of telehealth services universally, given the issues highlighted in this study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Air pollution is associated with several adverse health outcomes. However, heterogeneity in the size of effect estimates between cohort studies for long-term exposures exist and pollutants like SO 2 and mental/behavioural health outcomes are little studied. This study examines the association between long-term exposure to multiple ambient air pollutants and all-cause and cause-specific mortality from both physical and mental illnesses., Methods: We used individual-level administrative data from the Scottish-Longitudinal-Study (SLS) on 202,237 individuals aged 17 and older, followed between 2002 and 2017. The SLS dataset was linked to annual concentrations of NO 2 , SO 2 , and particulate-matter (PM10, PM2.5) pollution at 1 km 2 spatial resolution using the individuals' residential postcode. We applied survival analysis to assess the association between air pollution and all-cause, cardiovascular, respiratory, cancer, mental/behavioural disorders/suicides, and other-causes mortality., Results: Higher all-cause mortality was associated with increasing concentrations of PM2.5, PM10, NO 2 , and SO 2 pollutants. NO 2, PM10, and PM2.5 were also associated with cardiovascular, respiratory, cancer and other-causes mortality. For example, the mortality hazard from respiratory diseases was 1.062 (95%CI = 1.028-1.096), 1.025 (95%CI = 1.005-1.045), and 1.013 (95%CI = 1.007-1.020) per 1 μg/m 3 increase in PM2.5, PM10 and NO 2 pollutants, respectively. In contrast, mortality from mental and behavioural disorders was associated with 1 μg/m 3 higher exposure to SO 2 pollutant (HR = 1.042; 95%CI = 1.015-1.069)., Conclusion: This study revealed an association between long-term (16-years) exposure to ambient air pollution and all-cause and cause-specific mortality. The results suggest that policies and interventions to enhance air quality would reduce the mortality hazard from cardio-respiratory, cancer, and mental/behavioural disorders in the long-term., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Development of multimorbidity is common among cancer survivors due to their previous cancer, treatments, or changes in lifestyle. We summarized evidence on the prevalence, patterns, and determinants of multimorbidity among childhood and adult cancer survivors. We searched PubMed and EMBASE databases for articles reporting prevalence, patterns, and determinants of multimorbidity in cancer survivors. Finally, 23/500 articles were included. There was a large variation in the prevalence of multimorbidity (13-89%) among cancer survivors. Bone marrow transplantation, radiation, female sex, lower level of physical activity, increasing age, minority ethnicity, low-income, and low-education were associated with a higher prevalence of multimorbidity. Patterns of multimorbidity were both concordant and discordant. In conclusion, multimorbidity is highly prevalent and a major concern among cancer survivors. A personalized care plan that takes into account the identified risk may be beneficial to reduce the burden of multimorbidity and improve the quality of life among cancer survivors., Competing Interests: Declaration of Competing Interest The authors declare no competing interests with respect to this research. However, Daniel Boakye is an employee of Philip Morris Global Studio Limited, UK., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen's safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2 V617F , CALR ins5 or CALR del52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study's A'herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk., (© 2023. The Author(s).)

Our understanding of how STAG proteins contribute to cell identity and disease have largely been studied from the perspective of chromosome topology and protein-coding gene expression. Here, we show that STAG1 is the dominant paralog in mouse embryonic stem cells (mESCs) and is required for pluripotency. mESCs express a wide diversity of naturally occurring Stag1 isoforms, resulting in complex regulation of both the levels of STAG paralogs and the proportion of their unique terminal ends. Skewing the balance of these isoforms impacts cell identity. We define a novel role for STAG1, in particular its N-terminus, in regulating repeat expression, nucleolar integrity, and repression of the two-cell (2C) state to maintain mESC identity. Our results move beyond protein-coding gene regulation via chromatin loops to new roles for STAG1 in nucleolar structure and function, and offer fresh perspectives on how STAG proteins, known to be cancer targets, contribute to cell identity and disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiplex immunofluorescence (mIF) imaging can provide comprehensive quantitative and spatial information for multiple immune markers for tumour immunoprofiling. However, application at scale to clinical trial samples sourced from multiple institutions is challenging due to pre-analytical heterogeneity. This study reports an analytical approach to the largest multi-parameter immunoprofiling study of clinical trial samples to date. We analysed 12,592 tissue microarray (TMA) spots from 3,545 colorectal cancers sourced from more than 240 institutions in two clinical trials (QUASAR 2 and SCOT) stained for CD4, CD8, CD20, CD68, FoxP3, pan-cytokeratin, and DAPI by mIF. TMA slides were multi-spectrally imaged and analysed by cell-based and pixel-based marker analysis. We developed an adaptive thresholding method to account for inter- and intra-slide intensity variation in TMA analysis. Applying this method effectively ameliorated inter- and intra-slide intensity variation improving the image analysis results compared with methods using a single global threshold. Correlation of CD8 data derived by our mIF analysis approach with single-plex chromogenic immunohistochemistry CD8 data derived from subsequent sections indicates the validity of our method (Spearman's rank correlation coefficients ρ between 0.63 and 0.66, p ≪ 0.01) as compared with the current gold standard analysis approach. Evaluation of correlation between cell-based and pixel-based analysis results confirms equivalency (ρ > 0.8, p ≪ 0.01, except for CD20 in the epithelial region) of both analytical approaches. These data suggest that our adaptive thresholding approach can enable analysis of mIF-stained clinical trial TMA datasets by digital pathology at scale for precision immunoprofiling., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Intrathecal Drug Delivery Systems are underutilised in the management of refractory cancer pain despite evidence of their efficacy. Not all patients who are offered this treatment modality accept it. There is no current evidence that indicates if the use of intrathecal drug delivery systems impacts on place of care for patients with cancer related pain., Aims: This service evaluation compared place of care, place of death and morphine equivalent daily dose at end of life for patients in whom Intrathecal Drug Delivery was successfully established versus those who chose comprehensive medical management., Setting/participants: A retrospective longitudinal cohort study of 45 patients with cancer pain comparing those who had ongoing analgesia successfully delivered via an implanted Intrathecal Drug Delivery System ( n  = 28) with those who continued to receive comprehensive medical management ( n  = 17)., Results: There was a markedly greater time spent in the community in the intrathecal group than the medical management group (median 126.5vs 25.5 days; p  = 0.002) and a lower morphine equivalent daily dose at end of life (median 127.5vs 440.0 p  = 0.022)., Conclusion: In patients with advanced cancer, the successful establishment of intrathecal analgesia is associated with more time in the community and a lower morphine equivalent daily dose at end of life. The study has low numbers, and the sample was retrospectively selected. Nevertheless, these findings suggest the initial investment of time in an inpatient setting may be beneficial. Further research is required, using larger, prospective studies of patient outcomes in this setting., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The term "scanxiety" has been coined to describe the anxiety commonly associated with individuals undergoing cancer-related imaging. Despite the prevalence and severity of scanxiety across various clinical and demographic populations, there remains a significant lack of qualitative insights from existing studies that effectively capture patients' experiences of scanxiety in their own words. Therefore, this review addresses the following research question: What are the experiences of scanxiety distress among people affected by cancer across the cancer care continuum?, Data Sources: Following the PRISMA methodology, a meta-aggregation of qualitative studies was performed, encompassing patients of all age groups who had been diagnosed with cancer or were indicated for a cancer-related scan. Of the 556 articles screened, 15 were deemed eligible for inclusion in the analysis., Conclusion: The three overarching themes of 1) experience of "scan-itis," 2) experience of "patient-clinician support," and 3) development of self-management strategies reveal the complex and interconnected factors that influence scanxiety in individuals undergoing cancer-related imaging. These findings emphasized distress experienced by patients during the waiting period for scan results, the act of viewing the results, and even the delivery of "bad" news. Consequently, patients expressed a strong desire for increased information, communication, and empathy from attending healthcare providers. Patients also report a myriad of self-coping strategies to manage their scanxiety well before, during, and after their scan appointment., Implications for Nursing Practice: The study highlights the need for targeted interventions for those undergoing cancer-related scans, including increased awareness and education for health professionals regarding scanxiety., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The introduction of immunotherapy, in particular immune checkpoint inhibition, has revolutionised the treatment of a range of tumours; however, only a minority of patients respond to these therapies. Understanding the mechanisms by which different immune checkpoint inhibitors work will be critical for both predicting patients who will respond and to developing rational combination therapies to extend these benefits further. The initiation and maintenance of anti-tumour T cell responses is a complicated process split between both the tumour microenvironment and the tumour draining lymph node. As understanding of this process has increased, it has become apparent that immune checkpoint inhibitors can act both within the tumour and in the draining lymph node and that they can target both already activated T cells as well as stimulating the priming of novel T cell clones. Currently, it seems likely that immune checkpoint inhibition acts both within the tumour and in the tumour draining lymph node both reinvigorating existing clones and driving further de novo priming of novel clones. The relative contributions of these sites and targets may depend on the type of model being used and the timeline of the response. Shorter models emphasise the effect of reinvigoration in the absence of recruitment of new clones but studies spanning longer time periods examining T cell clones in patients demonstrate clonal replacement. Ultimately, further work is needed to determine which of the diverse effects of immune checkpoint inhibitors are the fundamental drivers of anti-tumour responses in patients., (© 2023 The Author(s).)

Adequate reporting is essential for evaluating the performance and clinical utility of a prognostic prediction model. Previous studies indicated a prevalence of incomplete or suboptimal reporting in translational and clinical studies involving development of multivariable prediction models for prognosis, which limited the potential applications of these models. While reporting templates introduced by the established guidelines provide an invaluable framework for reporting prognostic studies uniformly, there is a widespread lack of qualified adherence, which may be due to miscellaneous challenges in manual reporting of extensive model details, especially in the era of precision medicine. Here, we present ReProMSig (Reproducible Prognosis Molecular Signature), a web-based integrative platform providing the analysis framework for development, validation and application of a multivariable prediction model for cancer prognosis, using clinicopathological features and/or molecular profiles. ReProMSig platform supports transparent reporting by presenting both methodology details and analysis results in a strictly structured reporting file, following the guideline checklist with minimal manual input needed. The generated reporting file can be published together with a developed prediction model, to allow thorough interrogation and external validation, as well as online application for prospective cases. We demonstrated the utilities of ReProMSig by development of prognostic molecular signatures for stage II and III colorectal cancer respectively, in comparison with a published signature reproduced by ReProMSig. Together, ReProMSig provides an integrated framework for development, evaluation and application of prognostic/predictive biomarkers for cancer in a more transparent and reproducible way, which would be a useful resource for health care professionals and biomedical researchers., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Melatonin, originally isolated from the mammalian pineal gland, was subsequently identified in many animal cell types and in plants. While melatonin was discovered to inhibit cancer more than 5 decades ago, its anti-cancer potential has not been fully exploited despite its lack of serious toxicity over a very wide dose range, high safety margin, and its efficacy., Areas Covered: This review elucidates the potential mechanisms by which melatonin interferes with tumor growth and metastasis, including its ability to alter tumor cell metabolism, inhibit epithelial-mesenchymal transition, reverse cancer chemoresistance, function synergistically with conventional cancer-inhibiting drugs while limiting many of their side effects. In contrast to its function as a potent antioxidant in normal cells, it may induce oxidative stress in cancer cells, contributing to its oncostatic actions., Expert Opinion: Considering the large amount of experimental data supporting melatonin's multiple and varied inhibitory effects on numerous cancer types, coupled with the virtual lack of toxicity of this molecule, it has not been thoroughly tested as an anti-cancer agent in clinical trials. There seems to be significant resistance to such investigations, possibly because melatonin is inexpensive and non-patentable, and as a result there would be limited financial gain for its use.

Purpose of Review: The complexity of the cancer cachexia phenotype has undoubtedly hindered researchers' understanding of this devastating syndrome. The presence and magnitude of host-tumour interactions are rarely considered during clinical decision-making within the current staging paradigm. Furthermore, treatment options for those patients who are identified as suffering from cancer cachexia remain extremely limited., Recent Findings: Previous attempts to characterise cachexia have largely focussed on individual surrogate disease markers, often studied across a limited timeframe. While the adverse prognostic value of clinical and biochemical features is evident, the relationships between these are less clear. Investigation of patients with earlier-stage disease could allow researchers to identify markers of cachexia that precede the refractory stage of the wasting process. Appreciation of the cachectic phenotype within 'curative' populations may aid our understanding of the syndrome's genesis and provide potential routes for prevention, rather than treatment., Summary: Holistic, longitudinal characterisation of cancer cachexia, across all at-risk and affected populations, is of vital importance for future research in the field. This paper presents the protocol for an observational study aiming to create a robust and holistic characterisation of surgical patients with, or at risk of, cancer cachexia., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)