Objectives This study examined the impact of the COVID-19 pandemic on presentation, referrals, diagnoses, stage distribution, primary treatment, and survival for Head and Neck Cancer (HNC) patients in Northern Ireland (NI) by analysing population-based patient level data collected during 2016-2023. Methods Individual-level data for all patients diagnosed with HNC available on the regional Cancer Patient Pathway System (CaPPs) during the period 2016-2023 was accessed to examine the number of cancers diagnosed, referrals, diagnosis, stage at diagnosis, and first treatment. Northern Ireland Cancer Registry (NICR) data up to 2021 was used to estimate the proportion of patients managed by the regional Multidisciplinary Team (MDT) and provide additional key characteristics and survival information. Data on activity in primary dental care (2016-2023) was accessed from the Northern Ireland Statistics and Research Agency (NISRA). Four time-periods were compared: pre-pandemic (PP: January 2016-March 2020), initial pandemic (IP: April 2020-March 2021), initial recovery (IR: April 2021-March 2022) and pandemic recovery (PR: April 2022-May 2023). Results Adult dental examinations in primary care dental services decreased by 78%, from a yearly average of 965,000 during the PP period to 218,000 during the IP period. The number of HNC patients assessed at the MDT did not change significantly over the period 2016-2023 (P>0.05) from an annual average of 322 in the PP period; 302 in the IP period; 315 in the IR period and 342 in RP. Although there was an increased proportion of late-stage HNCs (III and IV) in the IP period, this was only significant for the oral cancer subsite (51.7% PP versus 67.1% IP), with recovery in the following periods. There was a decrease in the number of HNC patients receiving surgery as first treatment, and conversely an increase in radiotherapy, across the four time periods. The number of patients undergoing surgery as first treatment type decreased from PP (136) to IP periods (119) and failed to recover to pre-pandemic levels (117 in PR). Short-term (2-year) observed and net survival was not significantly different for HNC patients diagnosed pre-pandemic compared to periods thereafter (IP, IR, RP). The largest decrease in 2-year net survival was found for oral cancer, from 64.7% (PP) to 57.3% (IR), which approached significance (P=0.06). Conclusion The COVID-19 pandemic had wide-ranging impacts on HNC in Northern Ireland with substantially fewer examinations provided in primary dental care; reduced HNC incidence in the IP period; higher proportions of late-stage disease (statistically significant in oral cavity only); fewer surgical treatments and lower survival. These patterns approached statistical significance for oral cancers, the site most likely to be detected through dental screening. Clinical Significance The COVID-19 pandemic severely impacted patient access to primary care dental services throughout NI, where clinical screening for HNC is undertaken by General Dental Practitioners (GDPs) as part of a dental check-up. This study demonstrates the importance of primary dental care services in the identification and early diagnosis of HNCs.

Abstract In colorectal cancer (CRC), tumours classified as consensus molecular subtype 4 (CMS4) have the worst prognosis and derive negligible benefit from chemotherapy. We previously described how repressed interferon-related signalling is associated with increased relapse in CMS4 tumours. Although the viral mimetic polyinosinic:polycytidylic acid, poly(I:C), can reduce liver metastasis in vivo, the initial phenotypic changes that underpin its anti-metastatic response remain poorly described, particularly in the immunosuppressed CMS4 tumour microenvironment. Here we characterise lineage-specific anti-metastatic responses induced by poly(I:C), including acute macrophage polarisation and a novel CMS1-like regenerative stem cell state, which drive pro-inflammatory microenvironmental changes in CRC. These insights enabled the development of tractable biomarkers that identify an “immune-warm” patient subset most likely to respond to poly(I:C), enriched for mismatch-repair proficient (pMMR), anti-inflammatory macrophages and CMS4-like features. The viral mimetic poly(I:C) offers a tailored treatment option for poor-prognostic tumours, by reprogramming stem cell states and activation of an innate-adaptive anti-metastatic response.

Preprint article submitted to a peer-reviewed journal. This version has not yet undergone peer review. Abstract: Precision oncology knowledge bases are central to interpreting cancer genomic variants and associating them with clinical implications, guiding therapeutic selection and molecular tumor board deliberations. Although clinical evidence informing these resources are broadly globally applicable, drug approvals and patient access to therapies are governed by regional regulatory and health system authorities. Currently, publicly available knowledge bases primarily represent regulatory approvals from the United States (US) Food and Drug Administration (FDA). Consequently, they may recommend inaccessible therapies or omit regionally approved options, limiting clinical utility in non-US settings. This disparity highlights an urgent need for region-specific precision oncology knowledge bases that account for local regulation and access. Here, we outline essential steps for establishing region-specific precision oncology knowledge bases by curating cancer drug approvals that have received local market authorization or reimbursement within their local health system. We do so in a project-agnostic manner to encourage distributed deployment, while also recommending the adoption of representation standards to support global interoperability. We envision a federated ecosystem of regionally contextualized knowledge bases that enable comparative analyses, which may provide a means to identify regional differences in treatment eligibility and pharmacoeconomic determinants of access. Building such frameworks will advance equitable precision oncology and ensure that genomic-driven cancer care benefits patients globally.

Post-polypectomy surveillance is a cornerstone of colorectal cancer (CRC) prevention, yet current reliance on colonoscopy poses challenges related to capacity, patient burden, and adherence.Amid growing interest in non-invasive strategies, this review evaluates the diagnostic performance, clinical applicability, and limitations of emerging alternatives, including faecal immunochemical testing (FIT), multitarget stool DNA (mt-sDNA), CT colonography (CTC), circulating tumour DNA (ctDNA), and colon capsule endoscopy (CCE), in the context of post-polypectomy surveillance. While FIT remains widely endorsed for low-risk populations, its limited sensitivity for flat adenomas and serrated lesions constrains its utility. mt-sDNA and CTC offer incremental improvements in detection but face cost-effectiveness, false-positive, and guideline limitations in surveillance. ctDNA holds promise for recurrence monitoring in high-risk CRC but remains investigational for adenoma surveillance. Evidence for CCE as a triage tool is emerging, though concerns persist regarding incomplete examinations, cost, and residual risk.Importantly, substantial heterogeneity in surveillance guidelines and suboptimal real-world adherence complicate evaluation and implementation of these modalities. Integration of molecular biomarkers and risk-adaptive strategies may support more personalised follow-up. However, robust comparative effectiveness studies that account for system-level and behavioural factors are essential to guide appropriate adoption. Non-invasive tools remain complementary, not yet replacements, for colonoscopy in post-polypectomy care.

BACKGROUND:The COVID-19 pandemic had an impact on cancer services globally. There is a crucial need to understand how the incidence and stage of major cancer types were affected internationally. We aimed to assess these metrics in seven countries within the International Cancer Benchmarking Partnership. METHODS:This population-based study used data on 2·6 million patients diagnosed with primary cancers of the colon, rectum, lung, prostate, female breast, ovary, and melanoma of the skin, between Jan 1, 2015, and Dec 31, 2020. Data were collected from cancer registries in 18 jurisdictions from seven countries participating in the International Cancer Benchmarking Partnership; Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK. The main outcomes of monthly cases and age-standardised incidence rates by site during the pandemic (April 1 to Dec 31, 2020) were compared with predictions for the same year based on pre-pandemic trends (Jan 1, 2015, to Dec 31, 2019). FINDINGS:Between April 1, and Dec 31, 2020, 55 713 (16%) of 347 666 expected cases were predicted to be missing, with the largest deficits seen for prostate cancer (24%), female breast cancer (18%), and melanoma (18%), and the smallest deficits seen for ovarian (4%) and lung cancer (8%). The largest difference between observed and predicted incidence rates for prostate cancer was seen in the UK (164·9 per 100 000 person-years predicted vs 101·4 per 100 000 person-years observed) and the smallest difference seen in Norway (164·1 vs 168·4). Reductions in incidence were greatest from April 1, to July 31, versus from Aug 1, to Dec 31, in 2020. The percentage deficits between observed and predicted cases were 54% (UK) and 36% (Ireland) for prostate cancer, 40% (UK) and 34% (Ireland) for breast cancer, and 40% (UK) and 35% (Canada) for melanoma. INTERPRETATION:The pandemic's greatest impact was during the first few months of societal lockdowns in 2020 when barriers in access to health care were greatest. Further research is needed to understand whether patients with a missed diagnosis were diagnosed at a later date and if they presented at a later stage. FUNDING:Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Higher Education Authority North South Research Programme, Health Data Research UK; Te Aho o Te Kahu, Cancer Control Agency New Zealand; New Zealand Cancer Society; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

PURPOSE:Using real-world data (RWD), we assessed the impact of diagnostic regulatory pathways on activation timelines and biomarker testing implementation in biomarker-driven clinical trials across Europe. METHODS:RWD from 132 Clinical Performance Study Applications (PSAs) and Ethics Committee (EC) submissions across 18 European Union Member States (EU-MS) and 2 non-EU countries that operate under the In Vitro Diagnostic Medical Devices Regulation 2017/746 (IVDR) were pooled for analysis. Statistical, outlier assessments and comparative analyses were performed to evaluate differences in timelines between submission pathways. Statistical significance was assessed using Welch's t-test and the Mann-Whitney U test. RESULTS:Mean combined approval time for all submissions (EC and PSA) was 129.39 days (median, 116.5; range 32-346). Sequential submissions averaged 139.97 days versus 121.11 days for parallel submissions, corresponding to a ∼15.6% longer timeline than sequential pathways (mean difference 18.86 days; p = 0.0411). Mean country-level combined approval timelines varied substantially across countries, ranging from 75.66 to 175 days among countries (n = 17) with ≥ 3 submissions. Substantial cross-country variability in operational implementation challenges was observed. CONCLUSIONS:Diagnostic approvals represent underrecognized bottlenecks in precision medicine (PM) trial activation, with approval timelines frequently exceeding those of Clinical Trial Applications (CTAs), median 108 days. Fragmented IVDR implementation has created substantial cross-country variability and uncertainty for trial activation. Biomarker strategies and diagnostic testing approaches should be thoughtfully constructed and considered pragmatically, as inefficient implementation may directly affect trial interpretability, efficacy assessment and regulatory success, substantially compromising trial delivery in Europe.

PURPOSE:Rural populations comprise around 27% of Europeans and face persistent challenges across the cancer pathway. Although rurality is recognised as a contributor to cancer inequalities, most evidence has historically been generated outside Europe. No comprehensive mapping of European rural cancer research exists and understanding where evidence is concentrated or absent is important for informing equitable cancer-policy planning. We mapped rural cancer research activity across Europe, including publication trends, geographical distribution, collaboration patterns, and thematic focus. METHODS:We conducted a bibliometric review in accordance with the BIBLIO Guidelines for Reporting Bibliometric Reviews of the Biomedical Literature. Data were retrieved from Scopus and Web of Science (1940-2025), processed in R (4.5.1), and analysed using the bibliometrix package. Analyses included annual output, citation metrics, country and institutional productivity, collaboration networks, thematic mapping, and Multiple Correspondence Analysis. RESULTS:A total of 2050 publications were analysed. Annual output increased at a growth rate of 6.04%. Research activity was unevenly distributed, with the UK, France, Germany, Poland, and Italy as the most productive countries. Collaboration networks were strong, especially among Western European nations. Thematic analysis showed a focus on screening, epidemiology, and specific tumour types, with limited research on treatment, survivorship, and service delivery-patterns relevant for European cancer policy. CONCLUSIONS:Rural cancer research in Europe is uneven and thematically narrow. Integrating rurality into cancer-inequality monitoring, incorporating rural indicators into EU policy frameworks, and strengthening research capacity in under-represented countries are timely, achievable steps to support more equitable cancer policy and planning.

OBJECTIVES:Unnecessary hospital admissions for palliative emergencies strain resources and may not meet patients' end-of-life preferences. This study evaluates the impact of a 3-year partnership between Macmillan Cancer Support and the Scottish Ambulance Service (SAS), launched in 2022, to strengthen community-based palliative care and establish alternative referral pathways. METHODS:A retrospective comparative analysis of SAS call data linked to emergency department (ED) outcomes was conducted for 2022 and 2023. We assessed changes in key metrics: acute-care hospital admissions, ambulance conveyance rates and 7-day mortality using χ2 and two-proportion z-tests. Costs were estimated using NHS data and scenario modelling of patient length of stay. RESULTS:A statistically significant 5.47% reduction in hospital conveyances was observed, equating to over 1600 fewer incidents conveyed to hospital. Estimated ambulance service savings totalled £570 871, with ED-related cost reductions from £3.6 to £5.6 million. A modest increase in 7-day mortality was noted, consistent with increasing acuity of patients managed in the community. CONCLUSIONS:The SAS-Macmillan collaboration demonstrates that targeted education, alternative referral pathways and integrated community care can reduce avoidable hospital admissions and improve efficiency. The initiative offers a scalable model to enhance patient-centred, community-based palliative and end-of-life care, aligned with patient preferences.

BACKGROUND:Individual-level microsimulation models are essential for evaluating colorectal cancer (CRC) screening programmes to capture the heterogeneity in disease progression. To ensure regional relevance, such models require detailed natural history structures and robust calibration to population-specific data. This study presents the development of the first CRC natural history microsimulation model tailored to Northern Ireland (NI) for evaluating the NI Bowel Cancer Screening Programme (NI BCSP). METHOD:The model simulates individual trajectories from adenoma onset to CRC diagnosis. Eight natural history parameters were calibrated to sex-specific CRC incidence data, initially using empirical (frequentist) calibration and Approximate Bayesian Computation (ABC) rejection, followed by the ABC-Markov Chain Monte Carlo (ABC-MCMC) algorithm. Other parameters were informed by NI-specific data sources. RESULTS:The frequentist and ABC rejection calibration approach's posterior distributions informed the prior distribution for the ABC-MCMC approach. ABC-MCMC was informative, yielding 55 parameter sets, but results were constrained by limited calibration targets and parameter identifiability. CONCLUSION:This is the first NI-specific CRC microsimulation model, providing a regionally tailored platform for evaluating screening strategies and supporting policy. Calibration was feasible in a data-limited context, but further refinement and additional targets are needed to improve parameter estimation.

Introduction As the global burden of cancer increases, international and national policymakers have made notable progress with the development of national cancer control plans (NCCPs). An increasing number of countries have published and updated their NCCPs; their design and implementation vary widely. Methods A literature scoping review was conducted to understand common challenges and progress in NCCPs across 20 representative countries based on a framework drafted to reflect the European Beating Cancer Plan and World Health Organisation’s guidance on NCCPs. In total, 103 sources were used for the analysis. These comprised of 42 official NCCPs, five accompanying documents, whilst the remainder (56) included other government official reports, academic, and grey literature. The research followed a standardised framework used to evaluate policies across five pillars: prevention, early detection, care, treatment, and quality-of-life. Results Across the 20 NCCPs, 65% assigned implementation of objectives to key stakeholders. A total of 25% of NCCPs did not include details on the allocated budget for implementation. Overall, there was variation in the definition of clear objectives and actionable targets across pillars. In the ‘Prevention’ pillar, most plans addressed reducing risk factors (80%), but less than half focus on increasing people’s awareness (40%). For ‘Early Detection’, 50% of NCCP included targets for cancer screening programmes, while 25% included targets for advanced diagnostics. NCCPs included well-defined objectives across ‘Care’ mechanisms, including centres of excellence (35%), multi-stakeholder engagement (50%), informed providers (40%), and cancer registries (55%). The pillar focused on ‘Treatment’ generally lacked actionable objectives, with low proportion of NCCPs having objectives related to early access (10%), access and reimbursement (15%), and none for regulatory approval or evidence requirements. Finally, plans demonstrated a relatively strong focus on ‘Quality-of-Life’ policy mechanisms, with clear goals and targets for palliative care (60%), support programmes (60%). ‘Research and Innovation’ and objectives related to these domains were highlighted across the cancer care continuum (65%). From a country perspective, NCCP Governance Scores (a measure of the inclusion of targeted, actionable objectives, allocated budgets, clearly assigned responsibilities, and monitoring reports) were highest in France, Ireland and Japan and lowest in Austria, Brazil, Norway, Saudi Arabia, Sweden and Turkiye, whereas NCCP Policy Indices (a measure of the inclusion of targeted, actionable objectives in each policy pillar) were higher in Belgium and Ireland and lower in Germany, Mexico, Switzerland The Netherlands and the US. Conclusion We propose the following recommendations to further enhance NCCPs: 1) Strengthen measurable and actionable targets, governance and evidence-based policy design and updates; 2) Ensure targeted allocation of funding and resources; 3) Promote equity through targeted action; 4) Future-proof investment goals in research; 5) Intensify efforts for integrated, accessible and interoperable cancer data; 6) Foster collaboration at sub-and above-country level to advance NCCP evolution; 7) Drive oncology research and innovation.

The European Code of Cancer Practice (ECCP) is a patient-centred framework for good clinical cancer practice, to improve outcomes for all of Europe’s patients [1]. Given challenges with applications to rural regions, the study aimed to explore the barriers and facilitators to implementing the ECCP in a rural, coastal, and urban context. We conducted semi-structured individual and group interviews with nine acute cancer professionals; nine non-clinical professionals; and four people with lived experience of cancer. Interviews were analysed using reflexive thematic analysis, underpinned by a constructivist approach. Three themes were developed across all groups. 1) ‘Fragmented communication pathways limits access’ to information-sharing between services, and about support and research, linked to workforce challenges. 2) ‘Geographic and infrastructural disparities between urban, rural, and coastal areas’ highlight barriers to accessing and delivering care, including transport issues, alongside place-specific facilitators to wellbeing. 3) ‘Unmet needs for living well during and after treatment’ denotes financial, work-related, and psychological challenges through treatment and survivorship. These barriers transcended across all ECCP domains. Workforce challenges that limit information-sharing about support and research, and gaps in post-treatment support, must be addressed to meet the ECCP aim to ensure equitable cancer care across geographical locations.

The shortage of well-trained personnel to deliver cancer care and conduct research remains a major obstacle to reducing disparities in cancer survival between high-income countries and low-income and middle-income countries (LMICs). This Commission set out to provide actionable guidance for strengthening the global cancer workforce with an emphasis on reducing these disparities. To better understand the extent of the rising global cancer burden and the resulting workforce needs, we modelled the current and future global landscape of 17 common cancers and 18 workforce personnel types. Among the modelled cancers, diagnosed incidence rates are projected to increase globally, especially in LMICs, driven by growing and ageing populations and changing risk factors. Crucially, we estimate that one in three cancers go undiagnosed worldwide, with more than 60% of cancers remaining undiagnosed in parts of Africa. We find that, among the diagnosed cancers in LMICs, late-stage presentation and a lack of essential treatments and qualified health professionals contribute to poor survival. According to our modelling, in 2050, 5-year net survival is projected to remain lowest in Africa (34%) and Asia (39%), while reaching beyond 60% in high-income settings. The global cancer workforce shortage is projected to reach about 100 million in 2050, with the largest shortages being for nurses (65 million) and diagnostic (radiology and pathology) specialists (16 million), especially in Africa and Asia. Comprehensive workforce scale-up of all personnel types is projected to avert 170 million cancer deaths and yield net economic benefits of US$120 trillion between 2030 and 2050, translating to a global return on investment of $4 per $1 invested. Focusing primarily on examples from sub-Saharan Africa and Latin America, we examine key obstacles to workforce development and retention in LMICs and propose pragmatic actions to address the workforce crisis. These actions include establishment of workforce and cancer registries; the creation of cross-sector and international partnerships to improve access to education and research training programmes as well as diagnostics, therapeutics, and equipment; and implementation of task-shifting, digital health, and artificial intelligence solutions, which could improve workforce productivity, further strengthening the case for investing in the cancer workforce. TRANSLATIONS: For the Spanish, Portuguese, French, Chinese (Mandarin), Arabic and Russian translations of the abstract see Supplementary Materials section.

A substantial gap persists in our understanding of specific cancer prevention, diagnosis and care needs of coastal communities. Despite growing policy attention to coastal inequalities, the current evidence-base is limited, with insufficient explanation of how and why cancer-related needs and outcomes vary across coastal geographies. Treating coastal areas as homogenous, or subsuming them within broader rural or urban categories, risks obscuring place-specific mechanisms that may contribute to inequalities, while also overlooking opportunities for targeted, place-sensitive interventions to improve cancer outcomes. This gap is increasingly salient considering recent policy developments. The new National Cancer Plan for England recognises that patients from deprived areas, particularly those in coastal and rural locations, distant from large academic centres, are less likely to be offered certain cancer-related care opportunities. The plan also commits to rebalancing cancer diagnostic and medical training places towards remote, rural and coastal areas, targeting investment in cancer nurse specialists and medical specialists in areas with greater need, and adopting more holistic approaches that involve non-clinical interventions to tackle inequalities. However, these ambitions have yet to be underpinned by a robust, conceptually grounded evidence-base specific to coastal cancer care. In response to the National Cancer Plan, our multidisciplinary team propose a conceptual framework for "coastal cancer care" relevant to both the UK and internationally. We identify key domains where a coastal context may influence cancer prevention, diagnosis, care, and survivorship, and present guiding principles to stimulate debate and inform future research and policy aimed at understanding and reducing inequalities in coastal settings.

Single-cell and multi-regional biopsy analyses. A, Schematic of scRNA-seq cohort derived from n = 6 CRC primary tumors. Boxplots showing ssGSEA scores for the Hallmark Epithelial Mesenchymal Transition gene set across the various cell types (B) and specifically between epithelial and stromal cells (C; from all six colorectal cancer tumors) in the scRNA-seq dataset (P < 2.2 × 10–16; Wilcoxon test). D, Comparison of ssGSEA scores for the Hallmark Epithelial Mesenchymal Transition gene set between epithelial and stromal cells in each primary CRC (n = 6) in the scRNA-seq dataset (all P < 2.2×10–16; Wilcoxon test). Epithelial cells are shown in green and stromal cells in pink. E, Schematic overview of the BOSS Biopsy cohort consisting of colon cancer resections from 7 patients each with up to n = 5 multi-regional biopsy samples. Heatmaps of ssGSEA scores for the Hallmark gene sets (F) and TF activity scores for the BOSS Biopsy samples (G). Samples are grouped according to patient of origin and the ESTIMATE Stromal Score of each biopsy sample is indicated by the ESTIMATE StromalScore bar at the top of the heatmap. Only the gene sets/TFs significantly and concordantly enriched in stroma or epithelium in both the LCM discovery and LCM validation cohorts are shown (from Fig. 2; Padj < 0.02 – Hallmarks; P < 0.05 – TFs). Gene sets/TFs with names/symbols colored orange were significantly enriched in stroma in the LCM discovery and LCM validation cohorts and gene sets/transcription factors with names/symbols colored blue were significantly enriched in epithelium in the LCM discovery and LCM validation cohorts. H, Scatterplots showing correlation between the ESTIMATE StromalScore and ssGSEA scores for the Hallmark Epithelial Mesenchymal Transition (left; Spearman rho = 0.96, P = 1.7e-08), KRAS Signaling Up (middle; Spearman rho = 0.87, P = 7.9e-07) and MYC Targets V2 (right; Spearman rho = −0.63, P = 0.00037) gene sets. Samples are colored by patient of origin. CRC, colorectal cancer.

Purpose Precision medicine (PM) holds the promise of transforming healthcare through tailored treatments for an individual’s disease, improving outcomes and reducing adverse effects, by delivering the optimal treatment, at the right dose, at the right time. This study explores the intricate interplay between pharmaceutical companies and diagnostic partners, highlighting the substantial opportunity costs and risks involved due to inherent complexities and challenges with successful PM implementation. Methods A total of 19 diagnostic business leaders, representing 12 companies, participated in structured interviews. Four key topics were explored: (1) the healthcare continuum; (2) partnerships and collaborations with pharmaceutical companies; (3) market dynamics and competition; (4) economic and logistical barriers to diagnostics and PM. These executives provided their perspectives, which were subsequently delineated in more detail through additional analysis. Results Interviews highlighted systemic misalignments hindering PM adoption. Inadequate, variable, and lengthy time-to-reimbursement, unclear clinical evidence standards, regulatory uncertainty, along with policies that slow technological advancement were cited as key barriers. High attrition rates and small patient populations, coupled with expensive and high failure rates for clinical trials compounded these challenges, with the burden from the European Union (EU) In-Vitro Diagnostic Regulation (IVDR) further adding complexity. Conclusion Our study revealed economic and logistical obstacles that must be overcome to deliver effective PM for patients. By understanding these complexities, stakeholders can better navigate the path forward, fostering more effective partnerships and delivering innovative solutions to translate PM from attractive concept to clinical reality.

The ConfoundR resource enables stromal influence estimation in cancer tissue. A, Schematic overview of the cohorts and analyses available within the ConfoundR app, accessible via https://confoundr.qub.ac.uk/. B, Expression Boxplots analysis module of ConfoundR enabling the expression of a single gene to be compared between stroma and epithelium samples in each of the ConfoundR datasets. C, Expression Heatmap analysis module of ConfoundR enabling the expression of multiple genes to be visually compared between stroma and epithelium samples in each of the ConfoundR datasets. D, GSEA analysis module of ConfoundR allowing GSEA of existing gene sets from established gene set collections or custom user defined gene sets to be performed comparing stroma with epithelium in each of the ConfoundR datasets.

The European Cancer Pulse: From data intelligence to policy action Norbert Couespel 1 and Mark Lawler 1, 2 highlight the European Cancer Pulse, a critical tool in tracking cancer inequalities and influencing cancer policy in Europe. 2024 marks the 10th anniversary of the European Cancer Patient’s Bill of Rights (1) launch in the European Parliament on World Cancer Day. The Bill of Rights was underpinned by what, at the time, was the most extensive study of cancer inequalities in Europe (2). Despite the impact of the Bill of Rights (3), cancer inequalities continue to be a challenging issue in Europe; eliminating these inequalities has been a significant aim of Europe’s Beating Cancer Plan. (4) A critical component in successfully addressing cancer inequalities is cataloguing their existence and their nature – robust intelligence is required to categorise the many inequalities that may be experienced by cancer patients in Europe and their potential impact. (5) Regrettably, this task has proved challenging, with extreme fragmentation of the information available; additionally, much of the data may not be robust, hampering its provision in a timely fashion to influence action.

Targeting RAS mutant (MT) colorectal cancer (CRC) remains a difficult challenge, mainly due to the pervasiveness of RAS/MEK-mediated feedback loops. Preclinical studies identified MET/STAT3 as an important mediator of resistance to KRAS-MEK1/2 blockade in RASMT CRC. This dose escalation/expansion study assessed safety and initial efficacy of the MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in RASMT advanced CRC patients. In the dose escalation phase, patients with advanced solid tumours received binimetinib with crizotinib, using a rolling- 6 design to determine the maximum tolerable dose (MTD) and safety/tolerability. A subsequent dose expansion in RASMT CRC patients assessed treatment response. Blood samples for pharmacokinetics, MET biomarker and ctDNA analyses, and skin/tumour biopsies for pharmacodynamics, c-MET immunohistochemistry (IHC), MET in situ hybridisation (ISH) and MET DNA-ISH analyses were collected. Twenty patients were recruited in 3 cohorts in the dose escalation. The MTD was binimetinib 30 mg B.D, days 1–21 every 28 days, with crizotinib 250 mg O.D continuously. Dose-limiting toxicities included grade ≥ 3 transaminitis, creatinine phosphokinase increases and fatigue. Thirty-six RASMT metastatic CRC patients were enrolled in the dose expansion. Pharmacokinetic and pharmacodynamic parameters showed evidence of target engagement. Across the entire study, the most frequent treatment-related adverse events (TR-AE) were rash (80.4

BACKGROUND:The United Kingdom's (UK) diverse geography means many people live in rural and coastal areas, where cancer outcomes are often poorer than in urban settings. Devolution means that the four nations of the UK have distinct approaches to cancer care. Scotland, Wales, and Northern Ireland have recently published national cancer strategies, while England's new plan is expected later in 2025. This study examined UK cancer policy documents, to identify, how, and to what extent, rural or coastal issues were considered. METHODS:UK cancer policy documents from 2000 to 2024 were sourced via The International Cancer Control Partnership (ICCP) website (https://iccp-portal.org/), UK government sites and Google. Documents were searched for rural and coastal related terms. RESULTS:Fifty-five documents were included (England n = 17; Northern Ireland n = 10; Scotland n = 21; Wales n = 7). No recent policies included a specific section or explicit recommendations for rural or coastal cancer care. Across the policies, contextual analysis highlighted that terms to promote rural or coastal equity rarely appeared within recommendations. Northern Ireland gave more attention to rural issues than other nations, as evidenced by a rural needs impact assessment and supporting documents to inform Northern Ireland's Cancer Strategy 2022-2032. CONCLUSION:Despite sizeable rural and coastal populations facing specific health challenges across the UK, national cancer policies excepting Northern Ireland gave minimal guidance for delivering cancer care tailored to these communities. Other UK nations should consider adopting more rural-centric approaches like Northern Ireland. POLICY SUMMARY:Coastal and rural health issues have received policy attention via the Chief Medical Officer for England's annual reports (2021; 2023) and more recently in the UK Government's 10 Year Health Plan for England (July 2025). However, when it comes to high-level cancer policy across the UK, the needs of rural and coastal people with cancer are not being adequately or specifically recognised.