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Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

The European cancer burden is growing rapidly, with an estimated 2 million deaths a year according to the latest research. As almost half of cancers are diagnosed after the age of 65, and considering the aging European population, a tidal wave of cancer cases will sweep across Europe within the coming decades. Without major action, the additional number of annual cancer cases is expected to rise from 4.2 million to 5.2 million by 2040. If we are to reach plateauing numbers by 2040 (as a minimum goal), this would require 0.75% annual reduction in risk and 1% reduction in risk of death. These challenges call for attack from various angles, coordinated efforts, rational strategies, initiatives throughout the cancer trajectory, activities to reduce inequities, and implementation of evidence-based measures. In order to defeat the societal challenges of cancer through innovation, Europe will need to join forces and connect the European Commission and the member states, politicians and citizens, industries and patient associations. A cancer mission should thus unite the public and patient viewpoint to the perspective of cancer professionals. The authors describe a plan that has been agreed upon among some of the major European Cancer organizations and associations. This plan uses a cancer mission as a tool and must deliver robust medical evidence to patients and doctors through high-quality research delivering sustainable and affordable strategies for prevention, treatment, and follow-up.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high‐quality cancer care. European policy (EU Cancer Mission and Europe’s Beating Cancer Plan) is currently moving towards a mission‐oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes’ Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high‐impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals., This study reveals the attributes of cancer centres based on data from 40 large European cancer centres, showing that Comprehensive Cancer Centres have significantly greater output of peer‐reviewed publications and clinical trials than other centres, and that the quality of multidisciplinarity is well established in all accredited cancer centres.

Background: The prognosis of patients with non-small cell lung cancer (NSCLC) is traditionally determined by anatomic staging using the Tumor, Node, Metastasis (TNM) staging system. TNM staging neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying NSCLC patients at increased risk of recurrence after curative-intent surgery remains an important unmet need as adjuvant therapies are available that may reduce the risk of recurrence and improve patient survival. Methods: Digital Display Precision Predictor (DDPP), based on differential RNA expression in tumor versus normal tissue, was used to interrogate gene sets to determine their association with disease-free survival (DFS) in patients with non-small cell lung cancer (NSCLC) who underwent curative-intent surgery. Findings: Low versus high DDPP score was significantly associated with shorter DFS (highest recurrence risk): HR=1.88, 95% CI [1.2-2.9] (p=0.006) in all patients (n=120) and in patients with TNM stages 1-2 (p= 0.00051) (n=83). For patients with stages 1-2 and low DDPP (n=29), adjuvant chemotherapy was associated with improved DFS (p= 0.0041). High co-overexpression of CTLA-4, PD-L1 and ICOS in normal lung (28 of 120 patients), hypothesized to reflect the host immune status, was also significantly associated with decreased DFS (p= 0.0013) suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS (p=2.12E-11). Interpretation: We identified stage 1-2 NSCLC patients with high risk of recurrence who benefitted from adjuvant chemotherapy. Furthermore, identified a subset of NSCLC patients who may have poor post-surgery outcome related to an immunotolerant normal tissue profile that might be amenable to modulation by specific checkpoint blockade immunotherapies. Funding: European Union Frame Pprogram 6-funded project (Chemores FP6 Health, Grant 37 665). Declaration of Interest: Dr. Vladimir Lazar, Catherine Bresson, are full time employees of Worldwide Innovative Network (WIN) Association - WIN Consortium. Worldwide Innovative Network (WIN) Association - WIN Consortium is the owner of the patent family entitled Digital Display. The inventors are Dr. Vladimir Lazar, and Shai Magidi. Dr. Jean-Francois Martini, is a full-time employee and stockholder of Pfizer Inc. Dr. Susan Galbraith is a full-time employee and stockholder of AstraZeneca. Dr. Benjamin Solomon received honorarium for Advisory Board from AstraZeneca and Bayer. Shai Magidi receives consultancy from Worldwide Innovative Network (WIN) Association. Dr. Amir Onn receives consulting fees from Roche Israel, MSD Israel, Boehringer Ingelheim 552 and AstraZeneca. Dr. Enriqueta Felip receives advisory board and/or speaker’s bureau fee from Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-LaRoche, Glaxi Smith Kline, Janssen, Medical Trends, Medscape, Merck Sharp & Dohme, Merck Serono, Peptomyc, Peervoice, Pfizer, Puma, Regeneron, Sanofi, Springer, Syneos Health, Takeda, Touch Medical; on the board of Grifols, Independent member. Receives research funding from Fundacion Merck Salud, Grant for Oncology Innovation (GOI) EMD Serono. Dr. Josep Tabernero declares scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. Dr. Gerald Batist collaborates in formal clinical trial contracts, IITs and in joint grants funded by Canadian and Quebec governments with Roche, Merck, Novartis, Astra-Zeneca, Bayer, Esperas, Aurka, Caprion, MRM. Pr. Angel Porgador declares scientific consultancy role for PiNK Biopharma. Dr. Razelle Kurzrock has received research funding from Genentech, Merck Serono, Pfizer, Boehringer Ingelheim, TopAlliance, Takeda, Incyte, Debiopharm, Medimmune, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Omniseq, and Guardant, as well as consultant and/or speaker fees and/or advisory board for X-Biotech, Neomed, Pfizer, Actuate Therapeutics, Roche, Turning Point Therapeutics, TD2/Volastra, Bicara Therapeutics, Inc., and Biological Dynamics, has an equity interest in IDbyDNA and CureMatch Inc, serves on the Board of CureMatch and CureMetrix, and is a co-founder of CureMatch. Dr. Richard L. Schilsky’s institution (ASCO) receives research grants in support of a clinical trial that he directs from the following companies: AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Genentech, Lilly, Merck, Pfizer. Dr. Schilsky reports being a consultant to Cellworks, Clarify Precision Medicine, Bryologx, EQRx and Scandion Oncology. The remaining authors declare no competing interests. Ethical Approval: The bio-banking study was approved by the IMM’s Ethics Committee.

We undertook a cost-effectiveness analysis (CEA) to compare an exercise and nutritional program with the usual nutritional care concomitant to adjuvant chemotherapy in localized breast cancer patients. The CEA was designed as part of the interventional, controlled, randomized, single-center, open-label PASAPAS study. Breast cancer patients receiving first-line adjuvant chemotherapy at a French Comprehensive Cancer Center were randomized 2:1 to a 6-month exercise program of supervised indoor and outdoor group sessions in addition to usual nutritional care (exercise arm) or a usual nutritional care group receiving dietary and physical activity counseling (control arm). Costs were assessed from the French national insurance perspective (in Euros, 2012). Incremental cost-effectiveness ratios (ICERs) were calculated for four criteria: body mass index, waist circumference, body fat percentage, and estimated aerobic capacity. Uncertainty around the ICERs was captured by a probabilistic analysis using a non-parametric bootstrap method. The analysis was based on 60 patients enrolled between 2011 and 2013. Average intervention costs per participant were €412 in the exercise arm (n = 41) and €117 (n = 19) in the control arm. Total mean costs were €17,344 (standard deviation 9,928) and €20,615 (standard deviation 14,904), respectively, did not differ significantly (p = 0.51). The 6-month exercise program was deemed to be cost-effective compared with usual care for the estimated aerobic capacity. Multicenter randomized studies with long-term costs and outcomes should be done to provide additional evidence. Clinical trial: The PASAPAS study is registered under ClinicalTrials.gov. Trial registration ID: NCT01331772.

A comprehensive cancer approach covering the entire research–care–prevention continuum can achieve a 10‐year cancer‐specific survival for 75% of patients diagnosed in EU member states with well‐developed health care by 2030. To ensure access to a critical mass of patient biological and technological resources, infrastructures for translational research, clinical and prevention trials, and outcomes research are needed. Here, we provide recommendations for achieving key targets and prioritize research areas., A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research–care–prevention continuum has the potential to achieve in 2030 a 10‐year cancer‐specific survival for 75% of patients diagnosed in European Union (EU) member states with a well‐developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high‐quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science‐driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC‐like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long‐term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans‐border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence‐based advice.

International audience; Introduction: A mission-oriented approach to cancer care in Europe was proposed by Julio Celis and Dainius Pavalkis in 2017. The major proposed objective is to achieve long-term survival of 3 out of 4 cancer patients by 2030. Background: The authors are president or president-elect of Organization of European Cancer Institutes (OECI) EU Life or European Cancer Community Organization (ECCO). Results: The goal is laudable and ambitious. However, it can only be successful if it is coordinated with active involvement of all stakeholders and interacts with an already well-organized, recognized, and certified European Accreditation and Designation quality approach to identify and select the potential candidates to participate in such a virtual network. Conclusion: The building of a virtual European Cancer Institute based on coordinated networks should refer to unquestioned criteria using a solid and proven methodology operated by an independent arbitration body. The cancer community must share a fundamental responsibility to act collectively and in today's era of the World Wide Web, it is time to think out of the box and consider the possibility of establishing networks of networks.; Introduction : Une approche de la prise en charge du cancer en Europe axée sur la mission a été proposée par Julio Celis et Dainius Pavalkis en 2017. Le principal objectif proposé est de parvenir à la survie à long terme de 3 patients sur 4 atteints de cancer d'ici 2030. Contexte : Les auteurs sont président ou président élu de l'Organisation des instituts européens du cancer (OECI) EU Life ou de l'Organisation communautaire européenne du cancer (ECCO). Résultats : L'objectif est louable et ambitieux. Toutefois, il ne peut être atteint que s'il est coordonné avec la participation active de toutes les parties prenantes et s'il interagit avec une approche de qualité déjà bien organisée, reconnue et certifiée de l'accréditation et de la désignation européennes pour identifier et sélectionner les candidats potentiels à participer à un tel réseau virtuel. Conclusion : La construction d'un Institut européen du cancer virtuel basé sur des réseaux coordonnés devrait se référer à des critères incontestables en utilisant une méthodologie solide et éprouvée gérée par un organisme d'arbitrage indépendant. La communauté de lutte contre le cancer doit partager la responsabilité fondamentale d'agir collectivement et, à l'ère du World Wide Web, il est temps de sortir des sentiers battus et d'envisager la possibilité d'établir des réseaux de réseaux.

Pesticides have been associated with various pathologies, and there is growing evidence of pesticide presence in domestic environments. However, most available studies focused on a limited number of pesticides or households, and few have been conducted in Europe. We aimed to assess indoor pesticide contamination by screening the prevalence of 276 pesticides and ten pesticide metabolites, in French households from different agricultural and urban areas. We sampled indoor dust from 239 households in 2012, proximate to orchards (n = 69), cereals (n = 66) and vineyard (n = 68) crops, or from urban area (n = 36). we used cellulose wipes moistened with isopropanol and polypropylene dust traps to collect recent (7 and 30 days, respectively) and settled dust (6 months). Overall, 125 pesticides and piperonyl butoxide were detected at least once in households, mostly at low prevalence: 97 in recent dust, and 111 in settled dust. In recent dust, the most prevalent compounds were o-phenylphenol (168 households, 70%), pentachlorophenol (86, 36%), and piperonyl butoxide (82, 34%). In addition to agricultural pesticides, we found a high proportion of domestic and banned compounds in recent and settled house dust. Several pesticides were identified in house dust, from different pesticide groups and sources. Our results suggest that domestic usage and persistence of banned pesticides may contribute substantially to indoor pesticide contamination. Graphical abstract 97 pesticides detected in households' recent indoor dust.

Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed.Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively.Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.

Background: The “meeting-in-the-middle” (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case–control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites. Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk. Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93–1.62) and 1.40 (1.14–1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24–1.96) and 1.09 (1.03–1.15), accounting for a proportion mediated of 100% and 24%. Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk. Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators. Cancer Epidemiol Biomarkers Prev; 27(5); 531–40. ©2018 AACR.

Resume Contexte Le risque augmente de second cancer primitif (SCP) chez les enfants, adolescents et jeunes adultes traites pour un cancer, lie notamment aux traitements, doit inciter a une reflexion sur le suivi optimal de cette population et la prevention de ces SCP. Objectifs Synthese des donnees de la litterature sur les facteurs de risque de SCP (facteurs comportementaux et expositions professionnelles) et les strategies de prevention. Methode Recherche bibliographique dans PubMed. Mots-cles : « cancer [tiab] AND young adult [tiab] OR adolescent [tiab] OR childhood [tiab] AND prevention [tiab] AND survivors [mesh term] ». Resultats Vingt-sept articles ont ete retenus. Les enfants, adolescents et jeunes adultes ayant eu un cancer ont des comportements a risque comparables a ceux de leurs pairs concernant le tabagisme (10 a 29 %), l’alimentation et l’exposition solaire. En revanche, ils ont une activite physique reduite. Il existe peu d’etudes sur des strategies de prevention ciblees. Les etudes disponibles restent peu concluantes. Aucune etude n’a ete identifiee sur l’exposition professionnelle et le risque de SCP. Conclusions Le suivi de cette population doit prendre en compte les facteurs de risque de SCP a long terme. Des strategies de prevention adaptees doivent faire l’objet d’etudes complementaires.

Survival of children and adolescents and young adults (AYAs) treated for cancer has increased with improved treatments. However, there is still an increased risk of second primary cancer (SPC) in the long term compared with the same-age population, especially related to treatments. The follow-up of this population and the prevention of SPC are important issues. Therefore, this study aimed to review the available literature on cancer risk factors (lifestyle and occupational exposures) in children and AYAs previously treated for cancer in order to identify interventions that might be implemented to improve healthy behaviors in this population.PubMed was searched using the following terms: "cancer[Tiab] AND young adult[Tiab] or teen[Tiab] or childhood[Tiab] AND prevention[Tiab] AND survivors[Meshterm]."Twenty-seven articles were included. Children and AYA survivors of cancer have similar risk behaviors to their peers regarding tobacco, diet, and sun exposure. However, they have lower physical activity. Few studies on prevention strategies in this population were identified. Results of available studies remain inconclusive. No publications were found on occupational exposure and risk of second cancer.Children and AYAs treated for cancer are a population at risk and require specific effective prevention strategies.

L’Agence nationale de securite sanitaire de l’alimentation, de l’environnement et du travail (Anses) resulte de la fusion, intervenue le 1er juillet 2010, de l’Agence francaise de securitaire sanitaire des aliments (Afssa) et de l’Agence francaise de securite de l’environnement et du travail (Afsset). En reprenant les missions de ces deux entites, l’Anses offre une lecture transversale des questions sanitaires et apprehende de maniere globale les expositions auxquelles l’Homme peut etre soumis au travers de ses modes de vie et de consommation, ainsi que les caracteristiques de son

The aim of this paper is to draw the reader's attention to the problem of dissemination of costly innovations, particularly in the field of oncology, in a context of scarce resources.Comparison of five economic aggregates related to health and the gross domestic product captures the weight of this sector in the national economy but also its cost to the community. A focus on oncology shows that during the year 2004, the cost of cancer in France, all sites being taken into account, amounted to 10.9 billion euros and the societal cost to 32 billion euros (2% of gross domestic product). The cost of breast cancer (36% of all female cancers) reached 1.5 billion euros for treatment and 3.5 billion euros for societal expenses (0.2% of gross domestic product). Due to the significant, rapid expansion of these costs (+19.2% in 2006 and 18.5% in 2007 for diagnosis-related group outliers) but also to the scarcity of resources, the development of costly innovations remains problematic. This article, based on concrete examples of breast cancer treatment, provides information on the contribution of health technology assessment (particularly cost-utility and budget impact analyses) to public decision. Economic evaluation, in particular, cost-utility assessment, allows comparison of costs and consequences (generic result usually expressed in quality-adjusted life years) in order to prioritize diagnostic and/or therapeutic strategies and to make choices based on social acceptability. Budget impact analysis, without consideration of efficacy, makes it possible to balance the financing needs arising from the adoption of a costly innovation with the paying capabilities of a given institution.

L’information des personnes malades est un enjeu majeur de sante publique. Elle fait desormais partie des droits des malades, en reponse a leur demande croissante d’etre informes et impliques dans les decisions medicales qui les concernent. Depuis 1998, la Federation nationale des centres de lutte contre le cancer (FNCLCC) a mis en place un programme d’information et d’education des patients atteints de cancer et de leurs proches: les SOR SAVOIR PATIENT (SSP). Ce programme repose sur une methodologie respectant les criteres de qualite en matiere de redaction de documents d’informations destines aux patients. Le guide SSP Douleur et cancer a pour objectif de repondre aux questions des patients sur les douleurs du cancer et de les aider a participer activement a leur prise en charge. Il a ete elabore grâce a un travail pluridisciplinaire incluant des methodologistes, une linguiste, des specialistes de la douleur et du cancer, ainsi qu’une vingtaine de patients et de proches. Des focus groups, des entretiens semi-directifs et des questionnaires ont permis d’analyser et de prendre en compte les besoins d’informations des patients, ainsi que leur vecu de la douleur et leurs preoccupations. Ce guide se compose de huit chapitres qui peuvent se lire de facon independante, en fonction des besoins de chacun. Il aborde de nombreuses questions: qu’est-ce que la douleur ? Quelles sont les causes de douleur pendant un cancer ? La douleur est-elle un signe de gravite ? Comment l’evaluer ? Comment la traiter ? Faut-il avoir peur des opioides ? Comment vivre la douleur au quotidien ? … Dans la prise en charge de la douleur, les patients jouent un role central dont ils n’ont pas toujours conscience. Le guide Douleur et cancer leur donne des informations completes, des conseils et des outils pratiques pour participer, avec l’ensemble des soignants, a la prevention, a l’evaluation et au traitement de leurs douleurs. Ce guide ne se substitue pas a la relation patient-medecin, mais il la complete. Il peut egalement etre utilise dans une demarche d’education therapeutique du patient.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information developed in this program is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres,the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding nephroblastoma is an adapted version of various scientific publications and international clinical practice guidelines, validated by oncology experts and by the Nephroblastoma Committee of the French Society against Cancers and Leukaemias in children and adolescents (SFCE). It was elaborated with the active participation of parents and other family members. It is meant to provide a basis for the explanation of the disease, to help parents asking questions, and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 PARIS, Tel. (0033)1 76 64 78 00, www.fnclcc.fr). This document was validated at the end of 2005 and published in May 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding nephroblastoma and published in this edition of the Cancer et Radiotherapie, describe the physiopathology of nephroblastoma, as well as treatments and follow-up. The guide allows parents and relatives to better understand the disease and the treatments proposed. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

PurposeA cancer network of general or private hospitals of a French region was started in 1995 for improving quality of care and rationalizing medical prescriptions. The impact of implementing a clinical practice guidelines (CPG) project assessed conformity with guidelines in medical practice; significant changes were observed within the network, whereas no changes were observed in a control region without cancer network. In the present study, we evaluated the persistence of conformity to guidelines through a new medical audit.Patients and MethodsIn 1999, the hospitals of the previously compared experimental and control groups accepted to reassess the impact of CPG. A controlled transversal study was performed in the experimental group (cancer network) and in the control group (no regional cancer network). In 1996 (first audit) and in 1999 (present audit), all new patients with colon cancer (177 and 200 in experimental group and 118 and 100 in control group, respectively) and early breast cancer (444 and 381 in experimental group and 172 and 204 in control group, respectively) were selected.ResultsIn the experimental group, the compliance of medical decisions with CPG was significantly higher in 1999 than in 1996 for colon cancer (73%; 95% CI, 67% to 79% v 56%; 95% CI, 49% to 63%, respectively; P = .003) and similar for the two periods for breast cancer (36%; 95% CI, 31% to 41% v 40%; 95% CI, 35% to 44%, respectively; P = .24). In the control group, compliance was significantly higher in 1999 than in 1996 for colon cancer (67%; 95% CI, 58% to 76% v 38%; 95% CI, 29% to 47%, respectively; P < .001) and identical for the two periods for breast cancer (4%; 95% CI, 1% to 7% v 7%; 95% CI, 3% to 11%, respectively; P = .19).ConclusionThe CPG program for cancer management produced persistent changes in medical practice in our cancer network in terms of conformity with CPG.

RESUME Les auteurs missionnes par l’Office Parlementaire d’Evaluation des Politiques de Sante (OPEPS) ont revu l’ensemble de la litterature. Ils demontrent malgre les controverses recentes que le depistage du cancer du sein est justifie medicalement et economiquement. Apres avoir revu l’organisation du depistage et les cahiers des charges, les auteurs situent l’experience francaise en regard des recommandations europeennes et des autres organisations. Ils analysent les resultats, en particulier de l’effort 2003 du Plan Cancer et discutent les risques du depistage et le type d’information donne aux femmes.

Background Integrated multimodal care is needed for patients with Ewing sarcoma, which is the second most common primary bone malignancy in children and adolescence. Chemotherapy increases survival from less than 5% to 65–70% for patients with localized tumors and to 25–30% for those with metastases at diagnosis. Surgery is a major tool, whereas advances in imaging techniques have improved the indications for and the optimization of treatment. Radiotherapy remains useful, either alone or in addition to surgery, and new techniques (conformational RT and IMRT) will reduce short-term toxic effects. Pediatric oncologists do not outweigh surgeons or radiation therapists, but they are the ones who coordinate the medical team, which also includes pathologists and imaging specialists. Methods The point of view of the pediatric oncologist was assessed as follows: the place of chemotherapy in Ewing tumor treatment, the place of radiotherapy in Ewing tumor treatment (including why avoid radiotherapy when technically possible in children), and how to proceed into the future? The place of surgery as local treatment for Ewing tumors was also evaluated. Results These reviews show a dynamic and kaleidoscopic panorama of intense activity at the laboratory and clinical levels. Conclusions Though good survival rates have been achieved, improvements using entirely new approaches are needed. © 2003 Wiley-Liss, Inc.

N-myc amplification is a major prognostic factor in neuroblastomas and is systematically investigated by Southern blot or polymerase chain reaction (PCR). A retrospective study of N -myc amplification has been carried out using fluorescence in situ hybridization (FISH) in 97 fixed neuroblastomas. For each tumour, FISH was performed on the area that contained the most immature neuroblasts. Among these 97 neuroblastomas, 16 were amplified and 12 were not interpretable. FISH was not interpretable in six cases. All neuroblastomas with N-myc amplification detected by Southern blot/PCR were amplified with FISH, except three that were not interpretable. Four tumours that were not interpretable in Southern blot/PCR contained more than five copies of N-myc by FISH: one was aneuploid and three were truly amplified, containing more than ten copies of N-myc. Among these three patients, two died in a short time of their tumours. Ten cases were not amplified by Southern blot/PCR and showed more than five copies by FISH: four were aneuploid and two showed heterogeneous amplification, with a few cells clearly amplified whereas most were not. Four cases were amplified, of which two patients died of their tumours. This study confirms that when applied to the most immature areas of fixed neuroblastomas, FISH displayed a higher sensitivity than molecular techniques (p < 0.001) and could detect heterogeneous amplification. FISH could therefore become an important complementary procedure in assessing prognosis in neuroblastomas.

Pan-European collaboration in studies of novel therapies and treatment strategies in childhood cancer is playing an increasing role in the attempt to improve cure rates. Differences in the systems of various countries with regard to drug control and ethical issues may lead to problems and delays. This applies in particular to phase I/II studies in children where the ethical considerations may be complex. In this review, the systems in three large countries—UK, France and Germany—are reviewed and current moves within the European Community towards a more standard approach are discussed.

From 1984 to 1997, 57 consecutive patients with non-metastatic Ewing's sarcoma of the ribs were treated according to multimodal French Society of Pediatric Oncology (SFOP) protocols EW 84, EW 88 and EW 93. The results of treatment were reviewed and analysed. Median age was 12 years. 34 patients had large tumours (greatest tumour dimension ⩾8 cm); pleural effusion was noted in 26. A tumour-positive margin after surgery was noted in 15 patients. Histological response after chemotherapy was assessed in 34 patients. 34 patients received radiation therapy. With a median follow-up of 5 years, the projected overall and relapse-free survival rates were 69 and 62%, respectively. The major site of relapse was local. None of the following was significant in predicting relapse: tumour size, gender, age at diagnosis, existence of pleural effusion, level of rib tumour, rib component, type of local control, surgical margin (positive or negative). Response to chemotherapy was the sole significant prognostic factor (P=0.004). Patients with pleural effusion had a higher percentage of relapse if they were treated without local radiation therapy. Our study confirms the prognostic significance of response to initial chemotherapy. Radiation therapy may be withheld in selected cases, but seems necessary in patients with pleural effusion.

Introduction Dioxins are environmental and persistent pollutants mostly emitted from combustion facilities (e.g. waste incinerators, metal and cement industries). Known to be endocrine disrupting chemicals, dioxins are suspected to increase breast cancer (BC) risk. Although diet is considered the primary source of dioxin exposure, no previous study has been published on dietary dioxin exposure in relation to BC risk. We aimed to assess dietary dioxin exposure among women from the E3N cohort and estimate BC risk associated with this exposure. Methods The study included 63,830 women from the E3N cohort who completed a diet history questionnaire (DHQ) in 1993 and were followed until 2008. Dietary dioxin exposure was estimated by combining consumption data from the E3N DHQ and food dioxin contamination data from a French national monitoring program. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox models adjusted for BC risk factors. Results Mean dietary dioxin exposure was estimated at 1.3 ± 0.4 pg/kg body weight (BW)/day. A 0.4 pg/kg BW/d increase in dioxin intake was not associated with overall BC risk (HR = 1.00; 95% CI: 0.96, 1.05). A significant decrease in risk of estrogen receptor negative (ER-)/progesterone receptor negative (PR-) tumors was observed among post-menopausal women in the upper quartile of estimated dioxin intake (HR for Q4 vs. Q1: 0.65; 95% CI: 0.45, 0.96; P for trend across quartiles = 0.0463). Conclusions Overall, no association between estimated dietary dioxin exposure and BC risk was found among E3N women. Further studies should include both dietary and environmental exposures to determine whether low-dose dioxin exposure is associated with BC risk. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0536-9) contains supplementary material, which is available to authorized users.

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Purpose: (1) To improve survival rates in patients with Ewing's sarcoma (ES) or peripheral neuroectodermal tumours (PNET) using semi-continuous chemotherapy and aiming to peform surgery in all; (2) To identify early prognostic factors to tailor therapy for future studies. Patients and methods One hundred and forty-one patients were entered onto the trial between January 1988 and December 1991. Induction therapy consisted of five courses of Cytoxan, 150 mg/m2 × 7 days, followed by Doxorubicin, 35 mg/m2 i.v on day 8 given at short intervals. Surgery was recommended whenever possible. The delivery of radiation therapy was based on the quality of resection and the histological response to CT. Maintenance chemotherapy consisted of vincristine + actinomycin and cytoxan + doxorubicin. The total duration of therapy was 10 months. Results After a median follow-up of 8.5 years, the projected overall survival at 5 years was 66% and disease-free survival (DFS) was 58%. In patients treated by surgery, only the histological response to CT had an influence on survival: 75% DFS for patients with a good histological response (less than 5% of cells), 48% for intermediate responders and only 20% for poor responders (≥ 30% of cells), P < 0.0001. The initial tumor volume by itself had no influence on DFS in these patients. In contrast, the tumour volume had a strong impact on DFS in patients treated by radiation therapy alone. Age had no impact on outcome. Conclusion Therapeutic trials for localized Ewing's sarcoma should be based on the histological response to chemotherapy or on the tumour volume according to the modality used for local therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

Therapy in metastatic Ewing's sarcoma is reviewed using the methodology recommended by the guidelines project of the Federation of French Cancer Centres (FNCLCC) Standards, Options and Recommendation (SOR) Group. Twelve articles relating to conventional dose therapy and seven articles related to high-dose therapy were judged suitable for detailed appraisal. Rates of complete response (CR) at metastatic sites and local control were high using combinations of vincristine, actinomycin, cyclophosphamide and doxorubicin with radiation or surgery. With more recent regimens, including increased doses of alkylating agents and anthracyclines the relapse-free survival has increased from

Clinical practice guidelines (CPGs) have been defined as ‘systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances’ (Institute of Medicine, 1990). The aim is to inform the clinician and the patient of the current best clinical practice in a given situation, based on a synthesis of the available evidence. The ‘Standards, Options and Recommendations’ (SOR) project develops evidence-based CPGs in oncology and has been undertaken by the French National Federation of Cancer Centers (FNCLCC) since 1993 (Fervers et al, 1995). The project is a collaboration between the FNCLCC (a Federation of the 20 French comprehensive cancer centres) and specialists from French public universities, general hospitals and private clinics. The aim of the project is to increase the quality and efficiency of care given to cancer patients by developing, disseminating and implementing CPGs. SORs are designed to provide a decision guide for cancer specialists in the choice of strategies for the diagnosis, treatment and follow-up of cancer patients. The FNCLCC represents the regional cancer centres (CRCCs) as a collaborative body at national and international level and coordinates activity in scientific, economic and social domains. The CRCCs are public service hospitals and have a mission of multidisciplinary cancer care, education and research. Twenty-five percent of all cancer patients in France (240 000 new cases every year) are managed within the CRCCs. The remainder are treated in public universities, general hospitals and private clinics. The SOR project encompasses the progressive development of CPGs for the initial management of cancer in adults and children, for supportive care and control of symptoms in cancer patients and for the standardization of ‘good clinical practice’ throughout the various disciplines involved in cancer care. It has also undertaken the development of CPGs specifically for nursing and paramedical staff, as well as the provision of evidence-based information for patients.

Objective The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of de-escalating cell dose cohorts of CD34 + Thy1 + hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells. Materials and Methods The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34 + Thy1 + HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m 2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2–5) after an HSC transplant cell dose de-escalation/escalation design. Results Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 × 10 6 CD34 + Thy1 + HSCs/kg provided prompt engraftment (absolute neutrophil count >0.5 × 10 9 /L day 10; platelet count >50 × 10 9 /L day 13). A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34 + selected or unselected autologous transplantation, which did not correlate with the CD34 + Thy1 + HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34 + Thy1 + HSC product and showed a median tumor log reduction >3.12. Conclusions CD34 + Thy1 + HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable hematopoietic reconstitution at cell doses >0.8 × 10 6 CD34 + Thy1 + HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.

PURPOSE: The introduction of clinical practice guidelines (CPGs) and the increasing desire to harmonize clinical practices draw attention to the economic impact of these trends. In 1994, CPGs were introduced in a French Comprehensive Cancer Center (Centre Régional Léon Bérard, Lyon). We evaluated the application of these CPGs in addition to the consequences of harmonizing clinical practices with respect to the distribution of resources by specifically analyzing the posttherapeutic follow-up of patients with localized breast cancer. METHODS: A before-and-after analysis of the records of patients who received posttherapeutic follow-up for localized breast cancer as of either 1993 or 1995 was performed. Two hundred records were chosen at random, 100 from 1993 and 100 from 1995. Follow-up was continued for as long as possible and CPG compliance was studied for each year of the follow-up periods. RESULTS: Follow-up that was not CPG-compliant required a significantly greater amount of resources. This difference was due to neither consultations nor mammographies, but was due to other examinations that were systematically performed without any warning signs to justify them. Depending on the follow-up year, noncompliant follow-up cost the Social Security from 2.2 to 3.6 times more than compliant follow-up. A noticeable change in medical practices was observed after the introduction of CPGs in 1994. This was confirmed by a sharp decrease in mean Social Security expenditure per patient of more than one third between 1993 and 1995, regardless of the follow-up year considered. CONCLUSION: In the follow-up of patients with localized breast cancer, a large decrease in costs has been observed along with the evolution of medical practices toward CPG compliance. This finding is probably generalizable to other settings, but there is nothing that proves that it is applicable to other treatment strategies.

Summary Background: Patients with advanced solid tumors may be included in phase I clinical trials. In such studies, the benefit expected is generally lower than the likelihood of toxicity and may even be non-existent if the patient's life expectancy is too short. This study was performed to identify prognostic variables for toxicity and survival in patients who participate in phase I clinical trials. Patients and methods: One hundred fifty-four patients treated on a phase I clinical trial in our institute were evaluated retrospectively. Univariable and multivariable analyses of patients' characteristics were undertaken to determine their effects on the probability of grade 3 and 4 toxicity and on survival. Results: Grade 3 or 4 toxicity was experienced by 56 patients (36%): dosage level at entry (P < 0.001) and age over 65 years (P = 0.03) were independently associated with the risk of toxicity. Median overall survival was 5 months. The multivariable analysis identified performance status 2 or 3 (P < 0.001) and lactate dehydrogenase levels greater than 600 UI (P < 0.001) as independent adverse prognostic variables for overall survival. Using these two parameters, we determined a prognostic index which allowed us to discriminate three risk groups of patients with an observed median survival of 8.5, 4.5 and 1.5 months, respectively. Conclusions: Subgroups with different survival expectancy can be identified among patients who are eligible for phase I clinical trials. If confirmed, the proposed prognostic model may be useful for therapeutic decision making in palliative oncology.

Context: Economic evaluations are costly and cannot always be carried out locally. Therefore, decision-makers may wish to use studies already performed in other settings. Objective: To define a method for assessing the eligibility of published economic evaluations for transfer to a given health care system and apply it to the french health care system in the clinical situation of adjuvant therapy for women with breast cancer. Methods: (1) Literature search in six databases from 1982 to 1996; (2) critical appraisal of articles based on four inclusion criteria; and (3) assessment of the eligibility of the studies for transfer based on five indicators. Results: We identified 26 published economic evaluations concerning adjuvant therapy in women with breast cancer. Six (23%) met all four criteria used to select studies, but none of these studies were eligible for transfer to the french health care system. The main reason was that cost data was not reported in a transparent way. Conclusions: To improve the transferability of economic evaluations, we recommend that requirements for data provision in publications be standardized and international collaboration strengthened.

Summary This study evaluates histological response, long-term outcome, and toxicity in an intensive chemotherapy program given before surgery. Patients and methods Sixty-two patients (39 males, 23 females; median age 14) with biopsy, chest computerised-tomography, technetium bone-scan and magnetic resonance imaging, were enrolled. Primary localisations were femur (44%) and tibia (26%). Induction chemotherapy involved seven courses of high-dose methotrexate and two courses of HELP (ifosfamide, eldesine (vindesine), cisplatin (platinum)-doxo-rubicin. After surgery, patients received six courses of high-dose methotrexate and two courses of HELP-doxorubicin. Results Pre- and postoperative toxicities were similar. Fifty-nine patients underwent surgery: histological response was good in thirty-eight patients (64%) and poor in twenty-one (36%). Median follow-up is 57 months (range 30–80), with 77% overall survival and 59% progression-free survival. In a multivariate analysis, age under 10 years is the only prognostic factor that significantly correlates with outcome. Conclusions This regimen appears to increase histological necrosis, but associates with severe toxicity. Results for patients with less necrosis at surgery are encouraging. Future trials should determine the minimum effective doses to reduce toxicity. New drugs should be added.

Objective To review the epidemiological evidence on neuroblastoma and to use it in the framework of a statistical model to assess the value of screening children for this disease at different ages. Procedure A simple two-stage model of the disease is used to estimate the prevalence at screening from incidence and from the distribution of the length of the preclinical phase. Results It is shown that screening at 6 months would anticipate the diagnosis for a maximum of 25 cases per million. Given the detection rate of the existing programs, it would imply a 50% overdiagnosis. Furthermore, if the case with an anticipated diagnosis had a survival rate of 85%, the reduction in mortality would be at most 20%, whatever the age at screening. To detect such a reduction would need several millions of children to be enrolled in a trial. Conclusions Considering these results and the likely persistence of overdiagnosis when screening at 12 months, the epidemiological and statistical evidence plead against further research on neuroblastoma screening. Its efficacy can be evaluated with sufficient reliability from the present evidence: the likely small benefit on mortality does not compensate for the cost of overdiagnosis. Med. Pediatr. Oncol. 31:401–407, 1998. © 1998 Wiley-Liss, Inc.

Background Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized trial to determine the effect of each cytokine independently and in combination, and to identify patients who are best suited for this treatment. Methods Four hundred twenty-five patients with metastatic renal-cell carcinoma were randomly assigned to receive either a continuous intravenous infusion of interleukin-2, subcutaneous injections of interferon alfa-2a, or both. The main outcome measure was the response rate; secondary outcomes were the rates of event-free and overall survival. Predictive factors for response and rapid progression were identified by multivariate analysis. Results Response rates were 6.5 percent, 7.5 percent, and 18.6 percent (P

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.