BACKGROUND:In France, survival in the general population of women with breast cancer, according to stage at diagnosis has been poorly studied. The objective of this study was to estimate net survival and the excess mortality hazard (EMH) over time for breast cancer according to stage and age at diagnosis. METHODS:A representative sample of women diagnosed with invasive breast cancer between 2009 and 2015 was drawn from French cancer registries. Stage at diagnosis was defined using TNM classification. Net survival was estimated for each stage using the Pohar-Perme estimator. Excess mortality hazard were modeled using penalized flexible models as a function of time since diagnosis, age and stage. RESULTS:Among 9628 women identified, 47% were diagnosed at stage I and 7% at stage IV. Net survival decreased as stage increased. For stage IV, the EMH was highest in the first year after diagnosis compared to other stages. For stage II, however, the EMH increased until around three years after diagnosis and then decreased, while it reached a plateau for stage III. For stage I, EMH remained very low throughout follow-up. At five years of follow-up, older women had higher EMH across all stages. For stages I and II, younger women (aged 40) had higher EMH than women aged 50-60. CONCLUSION:This study provides updated population-based estimates of net survival and EMH over the five years following breast cancer diagnosis in France. Analyzing EMH allows us to better describe prognosis over time and to adapt the follow-up of women according to the stage at diagnosis.

Although cancer stage is a major prognostic factor, there are few studies providing population-based estimated of prostate cancer survival by stage at diagnosis, especially at a national level. Leveraging from a large sample of 10,783 cases of prostate cancer diagnosed over the period 2008-2015 from the French network of cancer registries, we provide the first estimates of prostate cancer net survival (NS) by PSA levels for mainland France. These results support that men with more advanced prostate cancers, approached by higher PSA values, had worse survival than men from the general population for the same age and geographical area. However, this group represented only 30% of the whole cases. In the majority of cases, which are characterized by lower PSA values and probably less advanced cancer, survival rates were similar and even higher to those of men from the general population for the same age and geographical area.

The joint spatial distribution of two count outcomes (eg, counts of two diseases) is usually studied using a Poisson shared component model (P-SCM), which uses geographically structured latent variables to model spatial variations that are specific and shared by both outcomes. In this model, the correlation between the outcomes is assumed to be fully accounted for by the latent variables. However, in this article, we show that when the outcomes have an unknown number of cases in common, the bivariate counts exhibit a positive "residual" correlation, which the P-SCM wrongly attributes to the covariance of the latent variables, leading to biased inference and degraded predictive performance. Accordingly, we propose a new SCM based on the Bivariate-Poisson distribution (BP-SCM hereafter) to study such correlated bivariate data. The BP-SCM decomposes each count into counts of common and distinct cases, and then models each of these three counts (two distinct and one common) using Gaussian Markov Random Fields. The model is formulated in a Bayesian framework using Hamiltonian Monte Carlo inference. Simulations and a real-world application showed the good inferential and predictive performances of the BP-SCM and confirm the bias in P-SCM. BP-SCM provides rich epidemiological information, such as the mean levels of the unknown counts of common and distinct cases, and their shared and specific spatial variations.

In France, the epidemiological surveillance of cancers is based on a multi-source surveillance system and a joint working program in partnership defined and performed by the French network of cancer registries (Francim), the Biostatistics-Bioinformatics Unit of Hospices Civils de Lyon, the French national public health agency and the French National Cancer Institute. This article presents the results of the 2014-2019 Cancer program. A questionnaire was completed for each of the 56 PTP projects, covering the implementation and financial resources committed. Among the 49 achieved projects were new estimates of incidence and survival produced at the national level for 70 types of cancer, with age-specific trends. Estimates of incidence were made at the district level for all French departments, even in districts not covered by a registry. The distribution of stage at diagnosis and social disparities in cancer incidence and survival were studied. The analysis of conditional net survival led to a better assessment of the risk of dying from cancer, which allowed improving access to insurance coverage and introducing a 'right to be forgotten' to people having a prior history of cancer. Contributing to the national and regional public policies with this innovative data, the outputs of the 2014-2019 Cancer program are successful. This makes a major contribution for the future of cancer surveillance, building on the ten-year French cancer protection, the crossing of databases and the implementation of a surveillance system at a geographical level lower than the district, remain challenging.

The incidence of early-onset breast cancer (EOBC) has recently been shown to be increasing over time in the US and the UK. Using national cancer registries data including 229,352 BC cases, we show that the incidence rate of EOBC in France increased steadily from 1990 to 2023, rising from 16.1 (95 % CI: 14.7-17.8) to 26.3 (95 % CI: 20.7-33.3) and from 98.7 (95 % CI: 93.8-103.7) to 131.2 (95 % CI: 115.8-148.7) per 100,000 person-years in women aged 30 and 40 years, respectively. This population-based study confirms that the incidence of EOBC is increasing over time in Western countries. Further research is needed to explain this trend, which may have implications for prevention and screening strategies.

En France, la surveillance épidémiologique des cancers repose sur un système de surveillance multi-sources et un programme de travail partenarial (PTP) définis et réalisés par le Réseau français des registres des cancers (Francim), le Service de biostatistique-bioinformatique des Hospices Civils de Lyon, Santé publique France et l’Institut national du cancer. Cet article présente le bilan du PTP Cancer 2014-2019.Un questionnaire portant sur la réalisation et les moyens financiers engagés a été complété pour les 56 projets du PTP. Parmi les 49 projets réalisés figurent des estimations nationales d’incidence et de survie produites pour 70 types de cancers avec des tendances par âge. Des estimations départementales d’incidence ont été produites pour l’ensemble des départements incluant les zones non couvertes par un registre. La répartition des stades au diagnostic et l’effet de la défavorisation sociale sur l’incidence et la survie ont été étudiés. L’analyse de la survie nette conditionnelle a conduit à mieux évaluer le risque de décéder du cancer dans le cadre de l’assurabilité des patients et à instaurer un « Droit à l’oubli » pour les personnes avec antécédent de cancer. Contribuant aux politiques publiques nationales et régionales par des données innovantes, le bilan du PTP Cancer 2014-2019 est fructueux. Il assure un apport majeur pour construire la future surveillance, en s’appuyant sur la Stratégie décennale de lutte contre les cancers 2021-2030. La viabilité des registres, la protection des données, le croisement des bases de données et le développement d’une surveillance infra-départementale, font partie des nombreux enjeux.

Access to healthcare and socioeconomic deprivation are intricately linked. No studies have been led to measure the effect of healthcare accessibility on mortality in patients with MS so far. The objective was to examine the influence of travel time to the expert MS centre and of the accessibility to primary healthcare services on excess mortality in MS. A retrospective observational cohort study recruited patients from 18 French MS expert centres, with an onset of MS between 1960 and 2015 and a follow-up of up to 30 years. Primary health facility accessibility was measured by the Spatial aCcessibility multiscAlar index. Specialist care accessibility was measured by road travel time to the expert MS centre. Excess death rates (EDR) and excess hazard ratios were studied using additive excess hazard models with multidimensional penalised splines. The study included 33,697 patients. Patients with relapsing-onset MS (R-MS) with a travel time of 40 min had the lowest EDR (Men: 1.2 deaths per 100 person-years (95

When describing relationships between variables and an outcome, dichotomization of continuous variables remains a widely used approach in medical research despite many drawbacks: the loss of information which reduces the statistical power to detect an association, the risk of misclassification and the problem of comparability of the results. Alternative approaches based on flexible functions are available and would allow to use all the information contained in the data and thus to model the possible non-linear relation between the continuous variable and the outcome. But these alternative approaches are rarely used probably because of a lack of clear guidance. This article aimed to illustrate the use of splines through an example based on hematological study. We showed the information provided by the plot of survival probabilities at a pre-specified time and according to the level of a continuous variable, thus displaying the trends of the studied phenomenon, as compared to a simple cut-off approach. In view of the major issues surrounding the patients' health, it is more than necessary to use the most powerful statistical approaches for greater precision in the understanding of health phenomena so that we may make more informed decisions. We hope this article will encourage the use of these approaches.

Contexte En France, à partir de 50 ans les femmes sont invitées à participer au dépistage organisé (DO) du cancer du sein. Toutefois, certaines réalisent un dépistage individuel (DI), dont la pratique est difficilement identifiable et donc rarement prise en compte dans les études de survie. L'objectif était d'identifier la pratique du DI et d'estimer l'excès de mortalité en fonction de la participation aux dépistages et des inégalités sociales. Méthode Quatre registres de cancers ont permis d'identifier des femmes de 50 à 74 ans diagnostiquées avec un cancer du sein entre 2009 et 2015, résidant dans quatre départements français. Les femmes ayant participé au DO ont été identifiées grâce aux structures de gestion du dépistage, et les femmes ayant bénéficié d'une surveillance mammographique (assimilé au DI) grâce à un appariement avec le Système national des données de santé (SNDS). La survie nette et l'excès de mortalité pour chaque groupe ont été estimé à l'aide de modèles paramétriques flexibles pénalisés en fonction du niveau de défavorisation EDI. Résultats Au total, 14 208 femmes ayant un cancer du sein ont été incluses (75 % DO, 10 % DI, 15 % non dépistées (ND)). La survie nette à 5 ans la plus élevée était chez les femmes DO (97 %). L'excès de mortalité était plus élevé chez les femmes ND que chez les femmes DO ou DI, indépendamment du suivi, de l’âge ou de l'EDI. Parmi les femmes ND, un gradient social était observé dès le diagnostic. Les femmes DI présentaient un excès de mortalité plus élevé que les femmes DO. Conclusion Cette étude a permis de distinguer le DO et le DI parmi une population de femmes atteintes d'un cancer du sein et montre le bénéfice du dépistage, en particulier du DO, sur la mortalité après cancer du sein et notamment dans les zones défavorisées.

BACKGROUND:In descriptive epidemiology, there are strong similarities between incidence and survival analyses. Because of the success of multidimensional penalized splines (MPSs) in incidence analysis, we propose in this pedagogical paper to show that MPSs are also very suitable for survival or net survival studies.METHODS:The use of MPSs is illustrated in cancer epidemiology in the context of survival trends studies that require specific statistical modelling. We focus on two examples (cervical and colon cancers) using survival data from the French cancer registries (cases 1990-2015). The dynamic of the excess mortality hazard according to time since diagnosis was modelled using an MPS of time since diagnosis, age at diagnosis and year of diagnosis. Multidimensional splines bring the flexibility necessary to capture any trend patterns while penalization ensures selecting only the complexities necessary to describe the data.RESULTS:For cervical cancer, the dynamic of the excess mortality hazard changed with the year of diagnosis in opposite ways according to age: this led to a net survival that improved in young women and worsened in older women. For colon cancer, regardless of age, excess mortality decreases with the year of diagnosis but this only concerns mortality at the start of follow-up.CONCLUSIONS:MPSs make it possible to describe the dynamic of the mortality hazard and how this dynamic changes with the year of diagnosis, or more generally with any covariates of interest: this gives essential epidemiological insights for interpreting results. We use the R package survPen to do this type of analysis.

In most developed countries, both organized screening (OrgS) and opportunistic screening (OppS) coexist. The literature has extensively covered the impact of organized screening on women's survival after breast cancer. However, the impact of opportunistic screening has been less frequently described due to the challenge of identifying the target population. The aim of this study was to describe the net survival and excess mortality hazard (EMH) in each screening group (OrgS, OppS, or No screening) and to determine whether there is an identical social gradient in each groups. Three data sources (cancer registry, screening coordination centers, and National Health Data System [NHDS]) were used to identify the three screening groups. The European Deprivation Index (EDI) defined the level of deprivation. We modeled excess breast cancer mortality hazard and net survival using penalized flexible models. We observed a higher EMH for "No screening" women compared with the other two groups, regardless of level of deprivation and age at diagnosis. A social gradient appeared for each group at different follow-up times and particularly between 2 and 3 years of follow-up for "OrgS" and "OppS" women. Net survival was higher for "OrgS" women than "OppS" women, especially for the oldest women, and regardless of the deprivation level. This study provides new evidence of the impact of OrgS on net survival and excess mortality hazard after breast cancer, compared with opportunistic screening or no screening, and tends to show that OrgS attenuates the social gradient effect.

Abstract Background During their care pathway, AML patients not admitted to Specialized Haematology Units (SHU) have less access to curative treatment. We aim to determine whether access to optimal curative treatment is affected by sociodemographic factors. Methods We included 1,033 incidents AML-cases diagnosed between 2012–2016 from three French “départements”. We considered patients managed in reference hospitals SHU within 5 days(n = 297) received “gold-standard” treatment. Treatment was "curative-treatment” if intensive chemotherapy and “non-curative” otherwise. Firstly, we trained a Gradian Boosting Machine (GBM) algorithm on 80%(n = 238) of "gold-standard" cases to learn how they were treated and validated the model on the remaining 20%(n = 59). Next, GBM predictions were contrasted with actual treatment. Using multivariable logistic regression, we examined how non-optimal treatment (discrepancy between predicted curative and observed non-curative treatment) was associated with sociodemographic factors. Patients with predicted non-curative treatment were excluded as uninformative on access to curative treatment (n = 471). Results The rate of “curative treatment” was 84.8% (252/297) for gold-standard patients vs. 33.5% (247/736) for others. The three most influential predictive factors in gold-standard patients were age (68.3%-influence), t-AML/MDS (15.8%), and the AML-others subtypes (5.4%). A total of n = 102(9.9%) patients were in non-optimal treatments. Living in Basse-Normandie (0.65-times;95%CI [0.5,0.8]) and over 30minutes from a reference hospital were strongly associated with a non-optimal treatment. Conclusions There are geographical disparities in access to optimal treatment, potentially linked to medical desert situations or medical system organization.

Background Based on preclinical studies showing that IDH-mutant (IDHm) gliomas could be vulnerable to PARP inhibition we launched a multicenter phase 2 study to test the efficacy of olaparib monotherapy in this population.Methods Adults with recurrent IDHm high-grade gliomas (HGGs) after radiotherapy and at least one line of alkylating chemotherapy were enrolled. The primary endpoint was a 6-month progression-free survival rate (PFS-6) according to response assessment in neuro-oncology criteria. Pre-defined threshold for study success was a PFS-6 of at least 50%.Results Thirty-five patients with recurrent IDHm HGGs were enrolled, 77% at >= 2nd recurrence. Median time since diagnosis and radiotherapy were 7.5 years and 33 months, respectively. PFS-6 was 31.4% (95% CI [16.9; 49.3%]). Two patients (6%) had an objective response and 14 patients (40%) had a stable disease as their best response. Median PFS and median overall survival were 2.05 and 15.9 months, respectively. Oligodendrogliomas (1p/19q codeleted) had a higher PFS-6 (53.4% vs. 15.7%, P = .05) than astrocytomas while an initial diagnosis of grade 4 astrocytoma tended to be associated with a lower PFS-6 compared to grade 2/3 gliomas (0% vs 31.4%, P = .16). A grade 2 or 3 treatment-related adverse event was observed in 15 patients (43%) and 5 patients (14%), respectively. No patient definitively discontinued treatment due to side effects.Conclusions Although it did not meet its primary endpoint, the present study shows that in this heavily pretreated population, olaparib monotherapy was well tolerated and resulted in some activity, supporting further PARP inhibitors evaluation in IDHm HGGs, especially in oligodendrogliomas.

Background The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to socio-economic status. Methods A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the Observatoire Fran??ais de la Scl??rose en Plaques. All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015. Initial phenotype was either relapsing-onset or primary progressive onset. Vital status was updated on January 1st 2016. Socio-economic status was measured by an ecological index, the European Deprivation Index and was attributed to each patient according to their home address. Excess death rates were studied according to socio-economic status using additive excess hazard models with multidimensional penalised splines. The initial hypothesis was a potential socio-economic gradient in excess mortality. Findings A total of 34,169 multiple sclerosis patients were included (88% relapsing onset (n = 30,083), 12% pro-gressive onset (n = 4086)), female/male sex ratio 2.7 for relapsing-onset and 1.3 for progressive-onset). Mean age at disease onset was 31.6 (SD = 9.8) for relapsing-onset and 42.7 (SD = 10.8) for progressive-onset. At the end of follow-up, 1849 patients had died (4.4% for relapsing-onset (n = 1311) and 13.2% for progressive-onset (n = 538)). A socio-economic gradient was found for relapsing-onset patients; more deprived patients had a greater excess death rate. At thirty years of disease duration and a year of onset of symptoms of 1980, survival probability difference (or deprivation gap) between less deprived relapsing-onset patients (EDI = ???6) and more deprived relapsing-onset patients (EDI = 12) was 16.6% (95% confidence interval (CI) [10.3%???22.9%]) for men and 12.3% (95%CI [7.6%???17.0%]) for women. No clear socio-economic mortality gradient was found in progressive-onset patients. Interpretation Socio-economic status was associated with mortality due to multiple sclerosis in relapsing-onset patients. Improvements in overall care of more socio-economically deprived patients with multiple sclerosis could help reduce these socio-economic inequalities in multiple sclerosis-related mortality. Funding This study was funded by the ARSEP foundation ???Fondation pour l???aide ?? la recherche sur la Scl??rose en Plaques??? (Grant Reference Number 1122). Data collection has been supported by a grant provided by the French State and handled by the ???Agence Nationale de la Recherche,??? within the framework of the ???Investments for the Future??? programme, under the reference ANR-10-COHO-002, Observatoire Fran??ais de la Scl??rose en Plaques (OFSEP). Copyright ?? 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: In cancer net survival analyses, if life tables (LT) are not stratified based on socio-demographic characteristics, then the social gradient in mortality in the general population is ignored. Consequently, the social gradient estimated on cancer-related excess mortality might be inaccurate. We aimed to evaluate whether the social gradient in cancer net survival observed in France could be attributable to inaccurate LT. Methods: Deprivation-specific LT were simulated, applying the social gradient in the background mortality due to external sources to the original French LT. Cancer registries’ data from a previous French study were re-analyzed using the simulated LT. Deprivation was assessed according to the European Deprivation Index (EDI). Net survival was estimated by the Pohar–Perme method and flexible excess mortality hazard models by using multidimensional penalized splines. Results: A reduction in net survival among patients living in the most-deprived areas was attenuated with simulated LT, but trends in the social gradient remained, except for prostate cancer, for which the social gradient reversed. Flexible modelling additionally showed a loss of effect of EDI upon the excess mortality hazard of esophagus, bladder and kidney cancers in men and bladder cancer in women using simulated LT. Conclusions: For most cancers the results were similar using simulated LT. However, inconsistent results, particularly for prostate cancer, highlight the need for deprivation-specific LT in order to produce accurate results.

Pour une maladie chronique à évolution longue, telle que la sclérose en plaques (SEP), il est difficile de déterminer si la maladie est à la cause du décès. Proposer une approche pour estimer la probabilité de décès par la SEP ainsi que la probabilité de décès par les autres causes sans recourir aux causes de décès. L’approche proposée repose sur le concept de « mortalité en excès », qui est obtenue en confrontant la mortalité « toutes causes » des patients SEP à la mortalité attendue en population générale. Les données proviennent de 18 centres experts participant à l’OFSEP. Les probabilités ont été estimées selon le phénotype initial de la SEP (rémittent : R-MS, progressif : PPMS) pour les hommes et les femmes après 30 ans de maladie. L’analyse portait sur 33 005 patients R-MS et 4519 PPMS (71 % de femmes au total, décès après 30 ans de maladie R-MS : 1522 (4,6 %), PPMS : 635 (14,0 %)). La probabilité de décéder de la SEP variait de 7,5 à 24,0 % chez les R-MS selon le sexe et l’âge de début, et de 25,4 à 36,8 % chez les PPMS. La probabilité de décéder d’autres causes variait de 2,8 à 42,8 % chez les deux phénotypes, soulignant que les autres causes contribuent, elles aussi, de façon importante au risque de décès. L’approche proposée présente un double avantage : d’une part, elle évite de recourir aux causes de décès contenus dans les certificats de décès, dont la qualité n’est pas toujours optimale ; d’autre part, elle est plus pertinente au plan conceptuel, car elle aide à définir ce que décéder de la SEP signifie et évite d’avoir à déterminer pour chaque sujet si le décès est (directement ou indirectement) causé par la maladie. Jusqu’à près d’un quart des patients R-MS et un tiers des patients PPMS décèdent de leur SEP dans les 30 ans après son début. La part des autres causes de décès rappelle l’importance du management des autres pathologies non liées à la SEP, et le renforcement de la prévention.

Background: The excess mortality observed in Acute Myeloblastic Leukaemia (AML) patients, partly attributed to unequal access to curative treatments, could be linked to care pathways.Methods: We included 1039 AML incident cases diagnosed between 2012-2016 from the 3 French blood cancer registries (3,625,400 inhabitants). We describe patients according to age, the medical entry unit and access to the specialised haematology unit (SHU) during follow-up. Multivariate logistic regression model was done to determine the association between covariables and access to SHU. A total of 713 patients (69%) had access to SHU during care.Results: The most common care pathway concerned referral from the general practitioner to SHU, n = 459(44%). The univariate analysis observed a downward trend for the most deprived patients. Patients who consulted in SHU were younger (66 years vs. 83, p < 0.001), and 92% had access to cytogenetic analysis (vs. 54%, p < 0.001). They also had less poor prognosis AML-subtypes (AML-MRC, t-AML/MDS and AML-NOS) (38% vs. 69%); 77% with de novo AML (vs. 67%, p < 0.003)], more favourable cytogenetic prognostic status (23% vs. 6%, p < 0.001), less comorbidities (no comorbidity = 55% vs. 34%, p < 0.001) and treatments proposed were curative 68% (vs. 5.3%, p < 0.001). Factors limiting access to SHU were age over 80 years (OR, 0.14; 95% CI, 0.04-0.38), severe comorbidities (OR, 0.39; 95% CI, 0.21-0.69), emergency unit referral (OR, 0.28; 95% CI, 0.18-0.44) and non-SHU referral (OR, 0.12; 95% CI, 0.07-0.18). Consultation in an academic hospital increased access to SHU by 8.87 times (95% CI, 5.64-14.2).Conclusion: The high proportion of access to cytogenetic testing and curative treatment among patients admitted to SHU, and the importance of early treatment in AML underlines the importance of access to SHU for both diagnosis and treatment.