An overall strategy based on regression models to estimate relative survival and model the effects of prognostic factors in cancer survival studies.

Relative survival provides a measure of the proportion of patients dying from the disease under study without requiring the knowledge of the cause of death. We propose an overall strategy based on regression models to estimate the relative survival and model the effects of potential prognostic factors. The baseline hazard was modelled until 10 years follow-up using parametric continuous functions. Six models including cubic regression splines were considered and the Akaike Information Criterion was used to select the final model. This approach yielded smooth and reliable estimates of mortality hazard and allowed us to deal with sparse data taking into account all the available information. Splines were also used to model simultaneously non-linear effects of continuous covariates and time-dependent hazard ratios. This led to a graphical representation of the hazard ratio that can be useful for clinical interpretation. Estimates of these models were obtained by likelihood maximization. We showed that these estimates could be also obtained using standard algorithms for Poisson regression

Incidence trends for potentially human papillomavirus-related and -unrelated head and neck cancers in France using population-based cancer registries data: 1980-2012.

Human papillomavirus (HPV) has been recently recognised as a carcinogenic factor for a subset of head and neck cancers (HNC). In Europe, France has one of the highest incidence rates of HNC. The aim of this study is to explore changes in HNC incidence in France, potentially in relation with infection by HPV. HNC were classified into two anatomical groups: potentially HPV-related and HPV-unrelated. Trends over the period 1980-2012 were analysed by an age-period-cohort model based on data from eleven French cancer registries. Among men, the age-standardised incidence rate (ASR) of HNC decreased in both groups, but less so for HPV-related sites as compared to unrelated sites, especially in recent years (annual percentage change [APC] over the period 2005-2012: -3.5% vs. -5.4%). Among women, the ASR increased in both groups, but more rapidly for HPV-related as compared to unrelated sites (APC over the period 2005-2012: +1.9% vs. -0.4%). This preferential growth of HPV-related versus unrelated HNC was observed in the cohorts born from 1930 to 1935. The differences in trends between possible HPV-related and HPV-unrelated sites suggest an increasing incidence of HNC due to HPV infection. The difference was less marked in men as compared to women, most likely because of a higher contamination in the HPV-related group by cancers due to tobacco or alcohol consumption. The pattern observed is consistent with observations made in other countries, with studies of HPV prevalence in HNC and the evolution of sexual behaviour in France

Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France.

BACKGROUND: The European Society of Breast Cancer Specialists (EUSOMA), which aims to standardize the quality of patient care in Europe, has defined quality indicators (QIs) for breast cancer (BC) care to assess compliance to current care standards. These QIs are a useful tool to evaluate care organizations. Only population-based studies are able to assess health system performance in "real-life" situations. This population-based study aimed to describe compliance with several EUSOMA QIs overall and according to patient and organizational factors in France. METHODS: 1 560 adult women with primary invasive non-metastatic BC diagnosed in 2012 were randomly selected among all incident BC from 16 French geographical areas covered by cancer registries. Twelve EUSOMA QIs were selected regarding diagnosis, treatment and staging. RESULTS: The minimum standard as proposed by EUSOMA was met for nine QIs related to pre-operative definitive diagnosis, multidisciplinary discussion and treatment (single surgery, breast conserving surgery (BCS) for small BC (<3cm), radiotherapy after BCS or mastectomy for regional BC (pN≥2a), hormonotherapy, adjuvant chemotherapy and trastuzumab). Low compliance was observed for sentinel lymph node biopsy (SLNB) and staging imaging. Adherence to guidelines was usually lower in older patients and in patients with comorbidities. Multidisciplinary discussion was positively related to adherence to guidelines for diagnosis, staging practices (SNLB, imaging) and systemic treatments. Compliance also varied by area of residence and by place of first treatment. CONCLUSION: This study provides the first current, comprehensive overview of BC quality care at a population level in France. The guidelines were correctly applied in percentage satisfying the EUSOMA standards for the diagnosis and treatment of BC, although staging practices (SLNB, imaging) can be improved. These results highlight the need for continuous measurement of adherence to guidelines to improve BC care

The performance of multiple imputation for missing covariate data within the context of regression relative survival analysis.

Relative survival assesses the effects of prognostic factors on disease-specific mortality when the cause of death is uncertain or unavailable. It provides an estimate of patients' survival, allowing for the effects of other independent causes of death. Regression-based relative survival models are commonly used in population-based studies to model the effects of some prognostic factors and to estimate net survival. Most often, studies focus on routinely collected prognostic factors for which the proportion of missing values is usually low (around 5 per cent). However, in some cases, additional factors are collected with a greater proportion of missingness. In the present article, we systematically assess the performance of multiple imputation in regression analysis of relative survival through a series of simulation experiments. According to the assumptions concerning the missingness mechanism (completely at random, at random, and not at random) and the missingness pattern (monotone, non-monotone), several strategies were considered and compared: all cases analysis, complete cases analysis, missing data indicator analysis, and multiple imputation by chained equations (MICE) analysis. We showed that MICE performs well in estimating the hazard ratios and the baseline hazard function when the missing mechanism is missing at random (MAR) conditionally on the vital status. In the situations where the missing mechanism was not MAR conditionally on vital status, complete case behaves consistently. As illustration, we used data of the French Cancer Registries on relative survival of patients with colorectal cancer

Total and partial cancer prevalence in the adult French population in 2008.

BACKGROUND: To provide estimations of partial and total prevalence of 24 cancer sites in France in 2008. The estimations of partial prevalence were compared with the previous estimations for 2002. METHODS: Nationwide estimations of incidence and survival data from cancer registries were used for partial prevalence. Nationwide incidence and mortality data were used to estimate total prevalence. RESULTS: At the end of 2008, in France, nearly 3 million people still alive had received a diagnosis of cancer. Of all prevalent cases, 36% were diagnosed 0 to 5 years earlier and 43% diagnosed 6 to 10 years earlier. The cancer sites with the highest prevalence were the prostate, the breast, and the colon-rectum. The changes in partial prevalence over 5 years (2002 to 2008) were considerable (+244,000 cases) and deemed to be highly related to changes in incidence. CONCLUSION: The present estimations update the French prevalence data and highlight the burden of cancer in the population, especially in the elderly. The methods of this study had the advantage of using recent incidence and survival data, which is necessary to show sudden changes in incidence trends and changes in survival that impact prevalence

Trends in excess mortality in follicular lymphoma at a population level.

BACKGROUND: Since the 1990s and since the development of humanised monoclonal antibodies in 1998, the treatment of non-Hodgkin lymphoma has undergone profound changes. Follicular lymphoma (FL) was the first to benefit from this treatment, and several clinical trials have shown a significant improvement in overall survival, but little information is available at a population level. OBJECTIVE: Our objective was to estimate changes in FL-specific mortality at a population level, with an appropriate methodology. METHODS: Two French retrospective population-based studies on FL were conducted, one from 1995 to 2004, in 1477 patients, and one from 1995 to 2010, in 451 patients. Trends in excess mortality rates (EMRs) according to age, sex, Ann Arbor stage and year of diagnosis were evaluated using the flexible model of Remontet et al. RESULTS: Trends in the EMR differed according to age at diagnosis and was higher in advanced stage (III, IV) in patients older than 65 yr. The EMR decreased linearly from 1995 to 2010. This decrease was more marked for advanced stages. CONCLUSION: FL-specific mortality decreased over the years of diagnosis, and the difference according to the lymphoma stage diminished in more recent years. However, progress in the management of FL was not able to erase age-related differences

Is breast cancer incidence increasing among young women? An analysis of the trend in France for the period 1983-2002.

International audienceThe purpose of the study was to describe the trend in the incidence of breast cancer in women under 40 in France for the period 1983-2002 and compare it with the trend observed in other age groups. Data from seven cancer registries were analysed. Annual percentage changes were estimated in different age groups using Poisson regression. During the period 1983-2002, breast cancer incidence in women under 40 increased regularly, with an estimated annual percentage change of 0.65 (95% CI: 0.03-1.26). In women aged over 40, the increase is more significant, particularly among women aged 50-74 (2.93% per year). The increase in breast cancer incidence in women under 40 was low and steady over the 20-year period considered. Even though young women did not experience such a major change in diagnostic practices as the development of screening among women aged 50-74, it is difficult to distinguish the effects of possible changes in risk factors and in diagnostic practices in the slight increase observed

Unbiased estimates of long-term net survival of hematological malignancy patients detailed by major subtypes in France.

Long-term population-based survival data detailed by cancer subtype are important to measure the overall outcomes of malignancy managements. We provide net survival estimates at 1, 3, 5 and 10-year postdiagnosis on 37,549 hematological malignancy (HM) patients whose ages were >15 years, diagnosed between 1989 and 2004 and actively followed until 2008 by French population-based cancer registries. These are, to our knowledge, the first unbiased estimates of 10-year net survival in HMs detailed by subtypes. HMs were classified according to the International Classification of Diseases-Oncology 3. Net survival was estimated with the unbiased Pohar-Perme method. The results are reported by sex and age classes. The changes of these indicators by periods of diagnosis were tabulated and the trends of the net mortality rates over time since diagnosis graphed. In all, 5- and 10-year age-standardized net survivals after HMs varied widely from 81 and 76% for classical Hodgkin lymphoma (CHL) to 18 and 14% for acute myeloid leukemia (AML). Even in HMs with the most favorable prognoses, the net survival decreased between 5- and 10-year postdiagnosis. Women had better prognoses than men and age at diagnosis was an unfavorable prognostic factor for most HMs. In patients <55 years old, the net mortality rate decreased to null values 5-year postdiagnosis in AML and 10-year postdiagnosis in CHL, precursor non-HL, chronic myelogenous leukemia, diffuse large B-cell lymphoma and follicular lymphoma. The prognoses improved for various HMs over the study period. The obtained unbiased indicators are important to evaluate national cancer plans

Cancer incidence and mortality in France over the 1980-2012 period: solid tumors.

BACKGROUND: Cancer incidence and mortality estimates for 19 cancers (among solid tumors) are presented for France between 1980 and 2012. METHODS: Incidence data were collected from 21 local registries and correspond to invasive cancers diagnosed between 1975 and 2009. Mortality data for the same period were provided by the Institut national de la santé et de la recherche médicale. The national incidence estimates were based on the use of mortality as a correlate of incidence. The observed incidence and mortality data were modeled using an age-period-cohort model. The numbers of incident cases and deaths for 2010-2012 are the result of short-term projections. RESULTS: In 2012, the study estimated that 355,000 new cases of cancer (excluding non-melanoma skin cancer) and 148,000 deaths from cancer occurred in France. The incidence trend was not linear over the study period. After a constant increase from 1980 onwards, the incidence of cancer in men declined between 2005 and 2012. This recent decrease is largely related to the reduction in the incidence of prostate cancer. In women, the rates stabilized, mainly due to a change in breast cancer incidence. Mortality from most cancer types declined over the study period. A combined analysis of incidence and mortality by cancer site distinguished cancers with declining incidence and mortality (e.g., stomach) and cancers with increasing incidence and mortality (e.g., lung cancer in women). Some other cancers had rising incidence but declining mortality (e.g., thyroid). CONCLUSION: This study reveals recent changes in cancer incidence trends, particularly regarding breast and prostate cancers