European Cancer Research Articles

Benefits of cross-border access to human genomes at scale for research and healthcare

Abstract Genomics data will soon be routinely generated and integrated into national healthcare systems. To maximise the potential of genomic medicine, data should be accessible for research where possible. This is the remit of ELIXIR, an intergovernmental organisation that brings together life science resources from across Europe. Innovative solutions are needed to ensure the validated research findings for disease or preventative medicine are then integrated into healthcare. To tackle this, the 1+MG initiative, a joint initiative of 25 EU countries, the UK, and Norway, aims to enable secure access to genomics and the corresponding clinical data across Europe for better research, personalised healthcare and health policy making. In the design and scale-up phase (B1MG project), recommendations and guidelines to advance towards the deployment of personalised medicine at a European scale have been produced, adopted by 1+MG and developed into a 1+MG framework. This includes guidance on data governance, standards, quality and infrastructure, recommendations on how to approach citizen engagement and a tool for countries to self-assess implementation into healthcare. The European Genomic Data Infrastructure (GDI) project supports the scale-up and sustainability phase of the 1+MG initiative, to deploy infrastructure across 24 countries to support the overall ambition. Recommendations are being used to promote governance and technical interoperability across European initiatives including the European Health Data Space (EHDS), and European Cancer Image Initiative (EUCAIM). The 1+MG will be established as a European Data Infrastructure Consortia in 2025 and will act as an Authorised Participant in the EHDS providing access to a permanent high-quality federated data collection of genomic and health data that will accelerate research, innovation and policymaking facilitating the deployment of genomic medicine across Europe.

Italian guidelines for age range and test interval in breast cancer screening programmes: GRADE-ADOLOPMENT of the European guidelines.

A guideline panel formulated a set of recommendations for breast cancer screening and diagnosis to implement clinical activities in Italy in alignment with the European Breast Cancer Guidelines on Screening and Diagnosis (European Commission Initiative on Breast Cancer-ECIBC). The panel issued national recommendations through adopting, adapting, and/or developing recommendations from the European guidelines (ADOLOPMENT approach). This process utilizes the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence to decision (EtD) framework. An additional PubMed search was conducted using search terms specific to Italy to tailor the EU guidelines to the national context. Nine articles were included as contextual evidence in the EtD. A total of 13 recommendations were finalized, either adapted or adopted to suit the national context. Organized breast cancer screening is strongly recommended for women aged 50-69 every 2 years, and it is conditionally recommended every 3 years for women aged 70-74, as well as every 1 or 2 years for women aged 45-49. Annual mammography received a strong recommendation against for women aged 50 and older. Developing shared national guidelines for the management of mammography screening will improve the standardization of processes across all settings, thereby promoting health equity.

Humoral Response to SARS-CoV-2 Vaccine-Boost in Cancer Patients: A Case Series from a Southern European Cancer Center

Background: Cancer patients face a greater risk of complications and death after contracting the SARS-CoV-2 virus. Booster doses of the COVID-19 vaccine were suggested to provide additional protection. This study aimed to assess how cancer patients’ immune systems respond to the booster shots and categorize their responses. Methods: We analyzed 735 samples from 422 individuals, including patients followed at the Portuguese Oncology Institute of Porto (IPO-Porto). Three cohorts were recruited, and blood samples were collected 3- and 6-months post-booster dose: cohort 1 cancer patients (also collected before the booster); cohort 2 cancer patients; and cohort 3 (healthy individuals). Humoral immune response was evaluated by analyzing IgG levels against the SARS-CoV-2 Spike (S) protein. IgG levels against the SARS-CoV-2 Nucleocapsid(N) protein was also analyzed in order to address previous contact with the virus. Results: Among Cohort 1 patients with solid tumors, when compared to pre-boost, IgG S levels increased 3 months after the boost and remained high after 6 months. Patients with hematologic tumors demonstrated lower IgG S levels at both timepoints. Comparing the IgG S levels among hematological tumors, solid tumors, and healthy individuals in both timepoints we observed that the healthy individuals had the strongest IgG S response, followed by the solid, and, lastly, the hematologic tumors. Solid tumor patients undergoing chemotherapy had reduced IgG S levels, especially those on high febrile neutropenia risk regimens. Conclusions: In conclusion, cancer patients have a weaker immune response to the SARS-CoV-2 vaccine, especially those with hematological cancers. Chemotherapy and febrile neutropenia risk further reduce booster effectiveness. Further research is needed to optimize vaccine timing for cancer patients undergoing chemotherapy.

Survey on current clinical practice in geriatric oncology: the individual experience in five European Cancer Centers.

To gather information from clinicians on how geriatric oncology models of care have emerged in different European countries and describe current practice in this clinical area. A semi-structured online interview was performed, exploring aspects related to implementation, perceived quality of care, and professional satisfaction. The centers participating in this interview showed significant differences in terms of resource allocation, team members, components of the comprehensive geriatric assessment (CGA), and CGA-driven interventions. High levels of professional satisfaction were expressed by all participants. This was deemed a consequence of a perception of increased quality in the provision of care and enhanced educational and academic opportunities. Interdisciplinary models of care in geriatric oncology, regardless of implementation details, seem to provide grounds for increased professional satisfaction and perception of better provision of quality of care. These characteristics could support promoting and further developing similar collaborations on a wider scale.

The effect of PSMA PET/CT on clinical decision-making of radical prostatectomy and pelvic lymph node dissection

Objective To evaluate the effect of prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) on clinical decision-making of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) after its utilization in daily clinical practice at an European high-volume cancer center. Materials and methods Patients who had unfavorable intermediate- and high-risk prostate cancer between 2017 and 2021 were included retrospectively and divided into two groups; those who staged using PSMA PET/CT (group 1) and those who staged using conventional modalities (group 2). Clinical decision-making of RP over nonsurgical treatments and f PLND were primary endpoints and evaluated using regression models. Results PSMA PET/CT claimed significantly more N1 (24.2% vs. 11.3%; P = 0.01; OR, 1.97; 95% CI, 1.18–3.28) but insignificantly more M1 disease (9.9% vs. 5.7%; P = 0.42; OR, 1.91; 95% CI, 0.39–9.23), compared with the conventional imaging modalities. miN0 stage was related to more RP decisions compared with cN0 stage (P < 0.001; OR, 1.91; 95% CI, 1.48–2.46). PLND decision-making was significantly driven by positive c\miN stage findings, which were more reliable when it was reported after a PSMA PET/CT examination (P < 0.001; OR, 35.55; 95% CI, 6.74–187.45 for conventional imaging modalities vs. P < 0.001; OR, 91.72; 95% CI, 11.25–747.56 for PSMA PET/CT). Conclusions Patients with no suspicion of lymph node invasion on molecular imaging (PSMA PET/CT) tended to be referred to RP more compared to radiological imaging. Also, the PLND decision was strongly driven by staging findings. Compared with conventional imaging, PSMA PET/CT findings were more reliable during PLND decision-making.

Survival and Health Care Burden of Children With Retinoblastoma in Europe

Studies on the epidemiology of retinoblastoma (RB) could lead to improvement in management. To estimate the incidence and survival of RB in European children and the occurrence of second primary tumors (other than RB) in these patients. This cohort study used population-based data from 81 cancer registries in 31 European countries adhering to the European Cancer Registries (EUROCARE-6) project. Data collection took place between January 2000 and December 2013. European children aged 0 to 14 years diagnosed with RB were included. Data were analyzed from May to November 2023. Diagnosis of RB with International Classification of Diseases for Oncology, Third Edition (ICD-O-3), morphology coded 9510-9514 (retinoblastoma) and malignant behavior (fifth digit of morphology code, 3). Annual incidence (per million children aged 0-14 years), 5-year survival (%), and the standardized incidence ratio (SIR) of subsequent malignant neoplasms. The study included 3262 patients (mean [SD] age, 1.27 [1.63] years; 1706 [52%] male and 1556 [48%] female) from 81 registries. Of these, 3098 patients were considered in trend analysis after excluding registries with incomplete time coverage: 940 in 2000 to 2003, 703 in 2004 to 2006, 744 in 2007 to 2009, and 856 in 2010 to 2013. The estimated overall European incidence rate was 4.0 (95% CI, 3.9-4.1). Rates among countries varied from less than 2 million to greater than 6 million per year. No time trend of incidence was observed in any area. The overall European 5-year survival was 97.8% (95% CI, 95.5-98.9; 3180 cases). Five-year survival was lower in Estonia and Bulgaria (<80%) and 100% in several countries. Twenty-five subsequent malignant neoplasms were recorded during follow-up (up to 14 years), with an SIR of 8.2 and with cases occurring at mean ages between 1.3 and 8.9 years across different sites. An increased risk was found for hematological tumors (SIR, 5) and bone and soft tissue sarcomas (SIR, 29). This study showed RB incidence remained stable at 4.0 per 1 000 000 European children aged 0 to 14 years from 2000 to 2013, but estimates varied among countries and differences in survival across countries persist. These data might be used to monitor RB management and occurrences of second tumors. The findings suggest future registry studies should aim to collect standardized RB stage at diagnosis and treatment to interpret disparities and potentially improve surveillance.

Skin cancer in Europe today and challenges for tomorrow.

One in every three cancers diagnosed is a skin cancer. Europe has the global lead in the number of UV-attributable cancer cases with the highest number of melanoma cases worldwide and the second highest number of keratinocyte cancers (KC). Further increases are expected in Europe for the coming decades. Projected increases are highest for KC with increases in incidence around 40% and increases in mortality around 50%, with KC mortality in males approximating melanoma mortality in females. The two main drivers for this skin cancer epidemic are ageing of the population but especially UV exposure. In conclusion, skin cancer represents a major challenge in the cancer field in Europe today and will continue to do so in the coming decades. This calls for a European skin cancer action plan intended to reduce avoidable UV exposure and to prepare the healthcare system to safeguard early diagnosis and treatment of skin cancer.

Lung Nodule Management in Low-Dose CT Screening for Lung Cancer: Lessons from the NELSON Trial.

Screening with low-dose CT (LDCT) in a high-risk population, as defined by age and smoking behavior, reduces lung cancer-related mortality. However, LDCT screening presents a major challenge. Numerous, mostly benign, nodules are seen in the lungs during screening. The question is how to distinguish the malignant from the benign nodules. Various studies use different protocols for nodule management. The Dutch-Belgian NELSON (Nederlands-Leuvens Longkanker Screenings Onderzoek) trial, the largest European lung cancer screening trial, used distinctions based on nodule volumetric assessment and growth rate. This review discusses key findings from the NELSON study regarding the characteristics of screening-detected nodules, including nodule size and its volumetric assessment, growth rate, subtype, and their associated malignancy risk. These results are compared with findings from other screening studies and current recommendations for lung nodule management. By examining differences in nodule management strategies and providing a comprehensive overview of outcomes specific to lung cancer screening, this review aims to contribute to the broader discussion on optimizing lung nodule management in screening programs.

Inadequate management of opioid-induced constipation in European cancer pain patients: results of a real-world, multicentre, observational study ("E-StOIC").

The objectives of the study were to determine the prevalence of (uncontrolled) OIC, relevant medications / interventions employed by healthcare professionals, and the additional strategies utilised by patients, amongst European patients with cancer pain. This study was a prospective observational study conducted at 24 research sites in ten European countries. Cancer patients receiving opioid analgesics for at least a week were recruited, and asked to complete a questionnaire including background information, single question (Are you constipated?), Rome IV diagnostic criteria for OIC, Bowel Function Index (BFI), and Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL). Participants were characterised as having / not having OIC on the basis of the Rome IV diagnostic criteria. 1200 participants completed the study. 59.5% met the Rome IV diagnostic criteria for OIC: only 61.5% that met these criteria self-reported constipation. 72% participants were prescribed a regular conventional laxative / peripherally acting mu-opioid receptor antagonist (PAMORA). However, only 66% took their prescribed laxatives every day. Many participants had utilised other strategies / interventions to manage their OIC. Furthermore, 27% had needed to use suppositories, 26.5% had needed to use an enema, and 8% had had a manual evacuation. The use of PAMORAs, and other novel effective medications, was relatively uncommon. The results of this study suggest that management in Europe is often inadequate, and this undoubtedly relates to a combination of inadequate assessment, inappropriate treatment, and inadequate reassessment.

An atlas of genetic effects on cellular composition of the tumor microenvironment.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.

Re-evaluating the Relationship between Cosmetic Products and Cancer: An Investigative Review of Paradigms

Abstract: Cosmetics are items that are used to glorify or change facial looks and appearance as well as provide fragrance to the body. Their main aim is to cleanse, beautify, facilitate attractiveness, and change physical looks. Women use many different beauty products, such as skin care, hair, perfume, oral hygiene, and nail care items, which may include harmful substances that are threatening to their health. The controversy around cosmetics and beauty products promoting cancer threat has grown over the previous few years. According to data from the European Cancer Registries, postmenopausal and very young women are now seeing an increase in the occurrence of breast cancer, which is the more frequent form of cancer in women. Genetic predisposition, long-term hormone replacement treatment, and various environmental variables, including air pollution, agrochemicals, alcohol, and specific consumer goods like cosmetic additives, are some of the causes of breast cancer. Additionally, the USFDA made all adverse event reports, including those involving concerns about cosmetics, publicly accessible via the Adverse Event Reporting System (CAERS) of the Centre for Food Safety and Applied Nutrition in 2016. In this period of modernization, CAERS is of limited use since there is a lack of different supporting data, such as demographic information, medical history, or linked product usage, and because the existing data is vulnerable to severe reporting bias. Despite the system's potential to protect the public's health, the database's future usefulness will depend on a wide range of reporting participants, more thorough reporting, and concurrent investments in regulatory science and enhanced molecular techniques.

Implementation of a remote symptom monitoring pathway in oncology care: analysis of real-world experience across 33 cancer centres in France and Belgium

Remote patient monitoring (RPM) of symptoms using electronic patient reported outcomes (ePROs) has been shown to reduce symptom burden and hospitalizations, increase dose intensity and improve quality of life of patients during systemic therapy being recommended by international guidelines in routine oncology practice. However, implementation in routine care has been slow and faces several challenges. In this study we report on the real-world multi-center implementation of a RPM pathway encompassing weekly patient symptom ePRO reporting with electronic alert notifications triggered to providers for severe or worsening symptoms. An RPM pathway was implemented in 33 European cancer centers in France and Belgium between November 2021 and August 2023. The implementation process followed a standardized phasic process of Exploration, Preparation, Implementation and Sustainment. Patient-level and system-level implementation metrics were collected and evaluated according to the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. Across the 33 cancer centers, the RPM pathway was implemented for 3015 patients cared for by 168 providers. The RPM pathway enabled effective and timely symptom management with 94.6% of all alerts (10,132/10,711) evolving to an improvement two weeks later, among which 88.4% (9468/10,711) showed ≥2 grades of improvement on the 5-point scale of the Patient-Reported Outcomes Common Terminology (PRO-CTCAE). The median time to alert management by the care team was 13 h 41 min (25th percentile: 1 h 42 min, 75th percentile: 1 day+ 19 h 54 min), with 80% (36,269/45,334) of alerts managed by a nurse navigator telephone call. Patient adherence with weekly ePRO reporting was 82% (2472/3015). In an experience survey, 87% (32/38) of providers were satisfied with integrating the solution into their organization and 90% (276/307) of the patients felt that ePRO reporting positively impacted their care. As of March 2024, the pathway has been maintained in all participating centers, with activation of an additional 18 centers following data lock, and reimbursement for this RPM pathway approved in France in October2023. These findings demonstrate the feasibility of implementing and maintaining an RPM pathway during routine care across a diverse group of cancer centers in the European setting, with high levels of patient and provider engagement, and positive clinical impact. Part of this work was funded Breast Cancer Research Foundation (Career Development Award to Maria Alice Franzoi) and Resilience (nurse navigation and technology support).

An International Registry Study of Early-Stage NSCLC treatment variations (LUCAEUROPE) in Europe and the USA highlighting variations

ObjectiveHarmonized European NSCLC incidence, treatment approach, and survival based on national tumor registries are unclear. Summary background dataSurgery has the potential to cure NSCLC and significantly prolong survival. This large-scale international study aimed to investigate treatment variations in Europe and the USA, as well as the determinants for its utilization. MethodsThe retrospective cohort study analyzed data from six European national population-based cancer registries (Belgium, Denmark, Estonia, Germany, the Netherlands, and Slovenia) and the US SEER database from 2010–2015. ResultsThe study computed cancer incidence, survival, and age-standardized proportions of the use of various therapies. Multivariable logistic regression models were used to assess associations between resection and demographic and clinical parameters. A total of 428,107 records were analyzed. Among all countries, Estonia had the highest surgical resection rate (79.3 %) and the lowest radiation rate (7.3 %) for stage I patients. The Netherlands had the highest rate of radiotherapy across all years of investigation and the lowest surgery rate between 2012 and 2015. The primary treatment for early-stage NSCLC showed significant international variation, with the USA having a decrease in surgical rates from 67.6 % to 59.5 %. Resection was less frequently performed as tumor stage increased, patients aged, other lung cancer besides adenocarcinoma was present, and when the tumor site overlapped multiple lobes. ConclusionsResection rates have declined in some studied European countries and the USA and resection rates vary substantially among countries. Interpretation of current scientific lung cancer evidence and international guidelines results in wide variations in patient treatment.

Estimating cure and risk of death from other causes of cancer patients: EUROCARE-6 data on head & neck, colorectal, and breast cancers

BackgroundTo estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. MethodsA new modelling approach, that corrects for patients’ extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40–79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. FindingsYoung male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. InterpretationNot considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients’ quality of life.

Increased risk of atrial fibrillation with low cardiovascular health: life essential 8 in a dutch population

Abstract Introduction The American Heart Association (AHA) introduced the concept of Life’s Essential 8 (LE8) to measure and monitor cardiovascular health (CVH) to prevent cardiovascular diseases. Purpose This study examined the association between LE8 and the incidence of atrial fibrillation (AF). Methods In total, 37,807 participants from the population-based European Prospective Investigation Into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included. The components diet, physical activity, sleep health, nicotine exposure, body mass index, blood glucose, blood lipids, blood pressure were all given a score between 0 and 100 and an overall LE8 score was created by averaging the component scores. The overall LE8 score was categorized into low cardiovascular health (CVH, 0-49), moderate CVH (50-79), and high CVH (80-100). AF cases were obtained through linkage with registries. A Cox proportional hazards model adjusted for age, sex, education level, heart failure, coronary heart disease, and alcohol consumption, was used to assess the association between LE8 and AF. Results The mean age of participants was 49 years ± 12 years and 75% of participants were female. During a median follow-up of 15.3 years (interquartile range: 14.1 – 26.5 years), 833 AF cases (2.3%) were identified. Compared to the participants with a high CVH score (19.5%), participants with a low CVH score (5%) had a 2 times higher hazard for incident AF (hazard ratio (HR) 1.99 [95% confidence interval (95%CI) 1.49 – 2.65]). Furthermore, a decrease in the number of ideal components was associated with a higher risk for incident AF (HR 1.11 [95%CI 1.05 – 1.18]). Conclusions The results show that a worse CVH, indicated by a lower LE8 score, is associated with an increased risk for incident AF. Preventing AF could potentially be achieved by implementing the LE8 score in clinical practice. Especially since LE8 is a tool that is easy to interpret and can be applied by healthcare providers to encourage patients to make improvements in the risk factors for AF.

468P Association of prior and concurrent malignancies with overall survival in a large European single-center gastroesophageal cancer cohort

468P Association of prior and concurrent malignancies with overall survival in a large European single-center gastroesophageal cancer cohort

Pro-inflammatory diets are associated with higher C-reactive protein and lower plasma concentrations of vitamins with anti-inflammatory potential, in the EPIC-Norfolk cohort

The development of multiple long-term conditions (MLTC) has been shown to be associated with low-grade chronic inflammation(1). The Dietary Inflammatory Index (DII®) is a literature-based dietary score that was developed to measure the potential impact of diet on the inflammatory status of an individual(2). In this study, we aimed to validate the DII® score against biomarkers, including high- sensitivity C-reactive protein (hs-CRP), and plasma concentrations of vitamin C, retinol and α- tocopherol in European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk participants, aged 39–79 years at baseline(3).The DII® score was calculated using a 130-item Food Frequency Questionnaire collected at baseline, between 1993 and 1997. The dietary intakes were adjusted to a 2000 kcal/day diet, to assess diet quality independently of diet quantity. Non-fasting serum cholesterol, hs-CRP, and plasma α- tocopherol, vitamin C and retinol concentrations were also measured at this time-point. Data collected via a self-administered Health and Lifestyle Questionnaire were used to establish classification of a number of variables. Analyses were conducted on sub-samples with a DII® score and measures of hs-CRP (8,034 men and 9,861 women), and concentrations of vitamin C (9,866 men and 11,702 women), retinol (3,673 men and 3,517 women) and cholesterol-adjusted α- tocopherol (3,623 men and 3,476 women). Analysis of covariance and linear regression were used to study associations across sex-specific quintiles of the DII® score (adjusted for age, BMI, smoking status, physical activity, social class and educational level), where a higher score indicates a more pro-inflammatory diet.Mean concentrations in men and women were 2.99 and 3.09 mg/L for hs-crp, 47 and 59 μmol/L for vitamin C, 53 and 50 μg/dL for retinol and 4.34 and 4.42 μmol/mmol for cholesterol-adjusted α- tocopherol, respectively. In both men and women, mean hs-CRP was higher if the diet was more pro-inflammatory (p-trend = 0.02 in men and 0.07 in women), while concentrations of vitamin C, retinol and α-tocopherol were significantly lower (p-trend &lt; 0.001). Positive associations for hs-CRP, but negative associations for plasma concentrations of vitamin C, retinol and α-tocopherol were evident in both men and women, after adjustments for covariates (p-trend &lt; 0.001). The differences between Q1 and Q5 adjusted means for hs-CRP, vitamin C, retinol and α-tocopherol were +9.4%, -22.1%, -3.9% and -8.6% in men and +7.9%, -17.5%, -4.8% and -7.6% in women, respectively.We observed statistically significant positive associations between the DII® score and hs-CRP, a well-known inflammatory biomarker, whilst significant negative associations were found for circulating concentrations of three anti-inflammatory vitamins, after adjustment for covariates. These findings indicate that the DII® score is a valid measure of the inflammatory potential of diet in these middle-aged and old adults, making it possible to study the inflammatory role of diet in MLTC development.

Single point of entry to the European precision cancer medicine trial network PRIME-ROSE.

e23024 Background: Over the last decades, there has been a surge in the development and approval of targeted drugs and immunotherapies for treating cancer patients, as seen by the 757 % increase in approvals by the FDA for new cancer treatments since 2000 (1). This has significantly impacted cancer care and contributed to improving overall survival in various cancer subgroups. However, access to these new treatments is constrained by the market access strategy of the patent-owning company and available knowledge of treatment effects. Only a few treatments have received pan-cancer approval from EMA or FDA, and most drugs receive market authorization per indication. As a result, there is a widening access gap between patients with different cancer types (2). Methods: Exploring the effect of biomarker-driven treatments in new cancer subtypes requires the ability to find patients with rare biomarkers. PRIME-ROSE is a European precision medicine network comprising 11 ongoing or soon-to-start national DRUP-like clinical trials testing registered drugs outside their current label ( www.prime-rose.eu ). Patients with relevant tumor biomarkers are identified and treated with matched drugs available in each trial’s drug portfolio. The ambition is to swiftly and systematically evaluate the effectiveness of approved precision cancer medicines in new indications through pragmatic trial designs and with RWE control cohorts, ensuring expansion into all relevant patient groups to maximize societal benefit. This is particularly relevant for rare cancers, which are enriched in precision medicine trials (3). Results: In PRIME-ROSE, the trials now share and aggregate data to build evidence faster and more effectively impact patient care by addressing key challenges in precision cancer medicine implementation (increasing the recruitment area to 71 million inhabitants). This will significantly reduce the time for filling treatment cohorts and contribute to closing the indication/drug-specific knowledge gap. In fact, several pharmaceutical companies have already shown their interest in and commitment to participating in PRIME-ROSE, as it offers the unique advantage of entering the trials in the network simultaneously (single point of entry) and with a floating allocation of treatment slots between trials, increasing efficiency in finding patients with specific biomarkers to fill treatment cohorts. Conclusions: A unified entry point to the PRIME-ROSE network is feasible and can facilitate building the knowledge base faster for label expansion and/or country-specific approvals/ reimbursement. National multi-stakeholder ecosystems that include pragmatic, RWE-controlled DRUP-like clinical trials may advance precision medicine implementation.

Abstract PO2-11-09: European Lobular Breast Cancer Advocates: Bridging the Geographical Gaps in Lobular Breast Cancer Education and Awareness

Abstract Introduction In 2019, Invasive Lobular Cancer (ILC) Patient Advocates attended the 3rd meeting of the European Lobular Breast Cancer Consortium (ELBCC), a scientific community focused on lobular research and treatment. European Lobular Breast Cancer Advocates (ELBCA) now have a network of ILC patient advocates across Europe. ILC is classified by the World Health Organisation as the most common Special Type of Breast Cancer. In 2022 there were 576,300 diagnoses of breast cancer in Europe, 15% ~86,500 were ILC. ILC is a histologically distinct breast cancer with diverse presentations including a tendency to metastasize to unique locations. Current endocrine therapies may have different effectiveness for ILC making treatment challenging. Current imaging tools are often unreliable with up to 30% of ILC tumours not identified on mammograms and detection is often delayed. Challenges There are no standardised European diagnostic or treatment protocols for ILC. ELBCA addresses this with collaborative efforts between ILC medical professionals and researchers. It’s a major challenge because each European country has a different health care system and economic policy structure. It’s also a challenge to streamline the translation of clinically accurate information to European patients in their own language. Not all European countries are members of the EU, there are a minimum of 24 official European languages. Established European breast cancer patient organizations often don’t distinguish between different histological subtypes. Current European policy and administrative processes have hindered the formation of a not-for-profit Advocacy Organization. Without such an organization, fundraising and collaborative efforts with others is difficult. Conclusions ELBCA has made significant progress towards raising awareness and increasing knowledge of ILC across Europe. Our poster will expand on these accomplishments as well as the following goals: Work with European and International ILC research and patient communities to better understand this unique histological subtype. Elevate ILC research priorities and inform European policy to recognize ILC as a distinct disease. Enhance education of ILC among primary HCP’s and patients. Establish a recognized European ILC Advocacy Organization and collaborate with established BC organizations. Attend major BC research and clinical conferences. Lobby to achieve increased funding for ILC research and clinical trials. Citation Format: Siobhan Freeney, Helene Bonval, Esther Geven, Lori Petitti, Rian Terveer, Claire Turner, Cathrin Brisken, Patrick Derksen, Christine Desmedt, Thijs Koorman, ADRIAN LEE, Steffi Oesterreich, Anne Salomon, George Sflomos, Karen Van Baelen, Tone Lien, Damir Vareslija, Sabine Linn. European Lobular Breast Cancer Advocates: Bridging the Geographical Gaps in Lobular Breast Cancer Education and Awareness [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-09.

Abstract PO5-19-02: I-PREPARE: International Prospective REgistry on Pre-pectorAl breast Reconstruction (EUBREAST 11R-NCT 05817175)

Abstract Background: Despite the progressive de-escalation of breast cancer (BC) surgery, mastectomy rates remain around 30-40%. Furthermore, up to 1/3 of BC patients undergo a contralateral risk-reducing mastectomy and around 40% of mutation carriers choose a bilateral intervention. To date, immediate breast reconstruction (IBR) with implants is the most commonly performed reconstructive procedure. After an initial experience with implants in subcutaneous positioning under the mastectomy flap in the seventies, this technique was abandoned due to a high rate of implant loss (28%), flap necrosis (13.5%) and capsular contracture (56%). For this reason, the positioning of the implant under the pectoralis major has become the standard of care. However, over time surgical techniques and implants have improved, resulting in decreasing implant loss, flap necrosis and capsular contracture rates. Moreover, biological/synthetic meshes have been used to cover the implant placed over the pectoralis major, thus avoiding to mobilize the muscle with some benefits in terms of reduced complications (no animation deformity, no chronic pain, no loss of muscular function), patients’ wellbeing, postoperative pain and recovery. Additionally, recent literature reported encouraging results with polyurethane breast implants in pre-pectoral positioning without any kind of implant coverage. Although these procedures are considered safe they were not evaluated in prospective randomized trials. In 2019 a joint consensus on pre-pectoral breast reconstruction (PBR) clearly recommended to properly audit the results in terms of surgical complications and patient-reported outcomes. Based on these premises the EUBREAST (European Breast Cancer Research Association of Surgical Trialists, www.eubreast.org) study group decided to launch a prospective international cohort study aimed at comparatively evaluating data on different surgical techniques of PBR with or without PMRT. Therefore, we will prospectively evaluate the utilization of PBR, including surgical, oncological, aesthetic and patients’ satisfaction and quality of life outcomes related to each type of surgical technique and the interaction with post-mastectomy radiation therapy (PMRT). Eligibility criteria: - Female patients age≥18 years - Signed informed consent - Patients undergoing mono/bilateral therapeutic mastectomy and immediate PBR Exclusion criteria - Patients not suitable for surgical treatment - Patients undergoing subpectoral reconstruction, reconstruction with tissue expander or autologous IBR Specific aims: The primary endpoint is implant-loss at 3 months defined as the unplanned removal or loss of the implant, as a result of infection or any other complication Secondary endpoints are infection, re-admission and re-operation rates, quality of life evaluated through BREASTQ Breast Reconstruction Module and EQ-5D-5L questionnaires on an App for patients before and after breast reconstruction at 6, 12, 24 months, early onset complication at 3 months, late-onset complications at 6, 12, 24 months, further surgery at 24 months, time to adjuvant therapy. Tertiary endpoints are further surgery, loco-regional recurrence, disease free survival, breast cancer specific survival, distant-disease free survival, overall survival, development of seroma/breast implant-associated anaplastic cell lymphoma. Statistics: We will use a single-arm design to assess the surgical safety of PBR through implant loss rate at 3 months which is expected to be ≤9% based on previous literature; 12% or greater will be regarded as unacceptably high. The assessment will be based on 1,112 patients. For this sample size calculation, power was set to 90%, and the two-sided alpha was set to 0.05. Allowing for a 10% loss to follow-up at 3 months, we aim at recruiting 1,236 patients. Accrual has not started yet. Funding: EUBREAST ETS Italy Contact: Oreste Davide Gentilini: gentilini@eubreast.org Citation Format: Rosa Di Micco, Maggie Banys-Paluchowski, Maria-Joao Cardoso, Jana de Boniface, Bahadir M. Gulluoglu, Orit Kaidar-Person, Thorsten Kühn, Maurizio Bruno Nava, Philip Poortmans, Shelley Potter, Nicole Rotmensz, Tanja Spanic, Marc Thill, Luzia Travado, Walter Weber, Oreste Davide Gentilini. I-PREPARE: International Prospective REgistry on Pre-pectorAl breast Reconstruction (EUBREAST 11R-NCT 05817175) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-02.