[Show abstract][Hide abstract] ABSTRACT: Estimations of survival rates are diverse and the choice of the appropriate method depends on the context. Given the increasing interest in multiple imputation methods, we explored the interest of a multiple imputation approach in the estimation of cause-specific survival, when a subset of causes of death was observed.
By using European Randomized Study of Screening for Prostate Cancer (ERSPC), 20 multiply imputed datasets were created and analyzed with a Multivariate Imputation by Chained Equation (MICE) algorithm. Then, cause-specific survival was estimated on each dataset with two methods: Kaplan-Meier and competing risks. The two pooled cause-specific survival and confidence intervals were obtained using Rubin's rules after complementary log-log transformation. Net survival was estimated using Pohar-Perme's estimator and was compared to pooled cause-specific survival. Finally, a sensitivity analysis was performed to test the robustness of our constructed multiple imputation model.
Cause-specific survival performed better than net survival, since this latter exceeded 100 % for almost the first 2 years of follow-up and after 9 years whereas the cause-specific survival decreased slowly and than stabilized at around 94 % at 9 years. Sensibility study results were satisfactory.
On our basis of prostate cancer data, the results obtained by cause-specific survival after multiple imputation appeared to be better and more realistic than those obtained using net survival.
BMC Medical Research Methodology 12/2015; 15(1):54. DOI:10.1186/s12874-015-0048-4 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To determine whether the risk of second primary cancer (SPC) among patients with bladder cancer (BCa) has changed over past years.
Materials and methods:
Data from ten French population-based cancer registries were used to establish a cohort of 10,047 patients diagnosed with a first invasive (T1 or greater) BCa between 1989 and 2004 and followed up until 2007. A SPC was defined as the first primary cancer occurring at least two months after a BCa diagnosis. Standardized incidence ratios (SIRs) of metachronous SPC were calculated. Multivariate Poisson regression models were used to assess the direct effect of the year of BCa diagnosis on the risk of SPC.
The risk of new malignancy among BCa survivors was 60% higher than the general population (SIR=1.60, 95% CI 1.51-1.68). Male patients presented a high risk of SPC of the lung (SIR=3.12), head and neck (SIR=2.19) and prostate (SIR=1.54). In multivariate analyses adjusted on gender, age at diagnosis and follow-up, a significant increase of the risk of second cancer of the lung was observed over calendar year of BCa diagnosis (p for linear trend .010), with a SIR increasing by 3.7% for each year (95% CI 0.9%-6.6%). However, no particular trend was observed regarding the risk of second cancer of the head and neck (p=.596) or the prostate (p=.518).
As the risk of SPC of the lung increased between 1989 and 2004, this study contributes more evidence to support promotion of tobacco-cessation interventions among BCa patients. This article is protected by copyright. All rights reserved.
BJU International 10/2015; DOI:10.1111/bju.13351 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Survival differences across Europe for patients with cancers of breast, uterus, cervix, ovary, vagina and vulva have been documented by previous EUROCARE studies. In the present EUROCARE-5 study we update survival estimates and investigate changes in country-specific and over time survival, discussing their relationship with incidence and mortality dynamics for cancers for which organised screening programs are ongoing.
We analysed cases archived in over 80 population-based cancer registries in 29 countries grouped into five European regions. We used the cohort approach to estimate 5-year relative survival (RS) for adult (⩾15years) women diagnosed 2000-2007, by age, country and region; and the period approach to estimate time trends (1999-2007) in RS for breast and cervical cancers.
In 2000-2007, 5-year RS was 57% overall, 82% for women diagnosed with breast, 76% with corpus uteri, 62% with cervical, 38% with ovarian, 40% with vaginal and 62% with vulvar cancer. Survival was low for patients resident in Eastern Europe (34% ovary-74% breast) and Ireland and the United Kingdom [Ireland/UK] (31-79%) and high for those resident in Northern Europe (41-85%) except Denmark. Survival decreased with advancing age: markedly for women with ovarian (71% 15-44years; 20% ⩾75years) and breast (86%; 72%) cancers. Survival for patients with breast and cervical cancers increased from 1999-2001 to 2005-2007, remarkably for those resident in countries with initially low survival.
Despite increases over time, survival for women's cancers remained poor in Eastern Europe, likely due to advanced stage at diagnosis and/or suboptimum access to adequate care. Low survival for women living in Ireland/UK and Denmark could indicate late detection, possibly related also to referral delay. Poor survival for ovarian cancer across the continent and over time suggests the need for a major research effort to improve prognosis for this common cancer.
European Journal of Cancer 10/2015; 51(51):2191– 2205. DOI:10.1016/j.ejca.2015.07.022 · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this epidemiological study was to describe the incidence, mortality and survival of ovarian cancer (OC) in France, according to age, period of diagnosis, and histological type.
Incidence and mortality were estimated from 1980 to 2012 based on data in French cancer registries and from the Centre for Epidemiology of Causes of Death (CépiDc-Inserm) up to 2009. Net survival was estimated from registry data using the Pohar-Perme method, on cases diagnosed between 1989 and 2010, with date of last follow-up set at 30 June 2013.
In 2012, 4615 cases of OC were diagnosed in France, and 3140 women died from OC. World population age-standardized incidence and mortality rates declined by respectively 0.6% and 1.2% per year between 1980 and 2012. Net survival at 5years increased slightly, from 40% for the period 1989-1993 to 45% for the period 2005-2010. Net survival varied considerably according to histological type. Germ cell tumors had better net survival at 10years (81%) compared to epithelial tumors (32%), sex cord-stromal tumors (40%) and tumors without biopsy (8%).
Our study shows a decline in incidence and mortality rates from ovarian cancer in France between 1980 and 2012, but net survival remains poor overall, and improved only slightly over the whole study period.
[Show abstract][Hide abstract] ABSTRACT: Receiver operating characteristic (ROC) research has been limited to binary choice. Recently, the method was generalized based on the Lehmann assumption also known as the proportional hazards specification. This model accommodates a variety of research questions such as covariate adjustments. By applying this method to three-class ROC analysis, simple analytical forms of ROC surface and volume under the surface were derived without and with covariates. Furthermore, the model parameters and the corresponding asymptotic variances were evaluated. Simulation studies were performed to assess the validity of our proposed method in finite samples and extension work for dimension higher than three-class is considered.
Journal of Statistical Computation and Simulation 02/2015; 85(3). DOI:10.1080/00949655.2013.831863 · 0.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of diseases that is known to carry a considerable risk of second primary cancer (SPC). However, little attention has been paid to SPC risk assessment according to NHL subtypes. Data from 10 French population-based cancer registries were used to establish a cohort of 7,546 patients with a first diagnosis of NHL (eight subtypes) between 1989 and 2004. Standardized incidence ratios (SIRs) of metachronous SPC were estimated. Among the 7,546 patients diagnosed with a NHL, the overall SPC risk was 25% higher than that in the reference population (SIR = 1.25 95% CI 1.15-1.36). In univariate analysis, the SPC risk differed by lymphoma subtype. Interestingly, multivariate analysis showed that SPC risk did not differ significantly across NHL subtypes after adjustment for the other covariates (p=0.786). NHL patients have an increased risk of SPC that is not influenced by the histological NHL subtype.
Leukemia and Lymphoma 02/2015; 56(10):1-23. DOI:10.3109/10428194.2015.1007505 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffuse WHO grade II and III gliomas (DGII/IIIG) are rare tumors, with few specific epidemiological studies. We aimed at describing the geographical distribution of a homogeneous series of histologically confirmed DGII/IIIG, over a four-year period (2006-2009), at a national level. The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase and data collected directly from every neuropathology department. Personal home addresses were collected for confirmed cases. For each region, the incidence of DGII/IIIG was analyzed and standardized on the age and sex distribution of the French population. The number of patients with newly diagnosed, histologically confirmed DGII/IIIG was 4,790. The overall crude rate was 19.4/10(6). To enable international comparisons, standardized rates were calculated as follows: 19.8/10(6), 18.8/10(6) and 16.0/10(6) (reference population, Europe, US and world, respectively). The geographical distribution by region showed significant differences, with higher incidence rates in Northeast and central parts of France. This work is the first studying the geographical distribution of a pure series of DGII/IIIG at a national level. It demonstrates significant heterogeneity in the distribution, and raises the question of the role of environmental and/or genetic risk(s) factor(s) for DGII/IIIG.
Journal of Neuro-Oncology 08/2014; 120(3). DOI:10.1007/s11060-014-1585-0 · 3.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this work was to detail the incidence and mortality trends of invasive and in situ breast cancer (BC) in France, especially regarding the development of screening, over the 1990-2008 period. Data issued from nine population-based cancer registries were studied. The incidence of invasive BC increased annually by 0.8 % from 1990 to 1996 and more markedly by 3.2 % from 1996 to 2003, and then sharply decreased until 2006 (-2.3 % per year), especially among women aged 50-69 years (-4.9 % per year). This trend was similar whatever the introduction date of the organized screening (OS) program in the different areas. The incidence of ductal carcinoma in situ steadily increased between 1990 and 2005, particularly among women aged 50-69 years and 70 and older. At the same time, the mortality from BC decreased annually by 1.1 % over the entire study period. This decrease was more pronounced in women aged 40-49 and 50-69 and, during the 1990-1999 period, in the areas where OS began in 1989-1991. The similarity in the incidence trends for all periods of implementation of OS in the different areas was striking. This suggests that OS alone does not explain the changes observed in incidence rate. Our study highlights the importance of closely monitoring the changes in incidence and mortality indicators, and of better understanding the factors causing variation.
Breast Cancer Research and Treatment 08/2014; 147(1). DOI:10.1007/s10549-014-3073-9 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to draw a picture of diagnostic assessment and patterns of care for rectal cancer in France using population-based registries data.
The study included a random sample of 669 cases of rectal cancers diagnosed in 2005.
Diagnostic assessment was performed by colonoscopy in 91.4% of the cases. An abdominal computed tomography was performed in 59.4% of the cases and chest computed tomography in 47.8%. An R0 resection was performed in 65.8% of cases and an R1/R2 resection in 16.1%. A rectal endosocography was performed in 40.4% and MRI in 10.4%. The sphincter was preserved in 73.6% of patients aged younger than 75 years of age and in 62.5% of those older than 75 years of age (P=0.002). In cases of R0 resection, neoadjuvant radiotherapy was performed in 47.8% of patients younger than 75 years of age and in 34.1% of older patients (P=0.007). Postoperative chemotherapy was administered in 23.9% of stage II and 67.8% of stage III resected patients.
The management of rectal cancers can be improved. Preoperative staging has not reached its full development; very few patients received neoadjuvant treatment, whereas adjuvant chemotherapy was often performed, although its benefit is still unclear. The management of elderly patients was less optimal than that of younger patients.
European journal of gastroenterology & hepatology 05/2014; 26(7). DOI:10.1097/MEG.0000000000000116 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few studies have investigated rectal cancer management at the population level. We compared how rectal cancers diagnosed in Italy (2003-2005) and France (2005) were managed, and evaluated the extent to which management adhered to European guidelines.
Samples of 3938 Italian and 2287 French colorectal cancer patients were randomly extracted from 8 and 12 cancer registries respectively. Rectal cancer patients (860 Italian, 559 French) were analysed. Logistic regression models estimated odds ratios (ORs) of being treated with curative intent, receiving sphincter-saving surgery, and receiving preoperative radiotherapy.
Similar proportions of Italian and French patients were treated with curative intent (70% vs. 67%; OR=0.92 [0.73-1.16]); the respective proportions receiving sphincter-saving surgery were 21% and 33% (OR=1.15 [0.86-1.53]). In about 50% of those treated with curative intent, ≥12 lymph nodes were harvested in both countries. The proportion receiving postoperative radiotherapy was higher in Italy than in France (25% vs. 11%, p<0.01), but French patients were more likely to receive preoperative radiotherapy (52% vs. 21%; OR=4.06 [2.79-5.91]).
The proportions of patients receiving preoperative radiotherapy and the numbers of lymph nodes sampled were low in both countries. Centralising treatment and potentiating screening would be practical ways of improving outcomes and adhering to guidelines.
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is the most common cancer in male in most Western countries, including France. Despite a significant morbidity and mortality to a lesser extent, the etiology of prostate cancer remains largely unknown. Indeed, the only well-established risk factors to date are age, ethnicity and a family history of prostate cancer. We present, here, the rationale and design of the EPIdemiological study of Prostate CAncer (EPICAP), a population-based case-control study specifically designed to investigate the role of environmental and genetic factors in prostate cancer. The EPICAP study will particularly focused on the role of circadian disruption, chronic inflammation, hormonal and metabolic factors in the occurrence of prostate cancer.
EPICAP is a population-based case-control study conducted in the departement of Herault in France. Eligible cases are all cases of prostate cancers newly diagnosed in 2012-2013 in men less than 75 years old and residing in the departement of Herault at the time of diagnosis. Controls are men of the same age as the cases and living in the departement of Herault, recruited in the general population.The sample will include a total of 1000 incident cases of prostate cancer and 1000 population-based controls over a 3-year period (2012-2014).The cases and controls are face-to-face interviewed using a standardized computed assisted questionnaire. The questions focus primarily on usual socio-demographic characteristics, personal and family medical history, lifestyle, leisure activities, residential and occupational history. Anthropometric measures and biological samples are also collected for cases and controls.
The EPICAP study aims to answer key questions in prostate cancer etiology: (1) role of circadian disruption through the study of working hours, chronotype and duration/quality of sleep, (2) role of chronic inflammation and anti-inflammatory drugs, (3) role of hormonal and metabolic factors through a detailed questionnaire, (4) role of individual genetic susceptibility of genes involved in biological pathways of interest. The EPICAP study will also allow us to study prognostic factors and tumor aggressiveness.Taken together, the EPICAP study will provide a comprehensive framework to go further in the understanding of prostate cancer occurrence and its prognosis.
BMC Cancer 02/2014; 14(1):106. DOI:10.1186/1471-2407-14-106 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although cancer survivors are known to be at greater risk of developing second primary cancer (SPC), SPC incidence estimates in France are thus far lacking. We used a multivariate approach to compute these estimates and analyzed the effect of patient characteristics (gender, age at diagnosis, first cancer site, year of diagnosis and follow-up) on SPC risk.
Data from ten French population-based cancer registries were used to establish a cohort of all patients diagnosed with a first cancer between 1989 and 2004 and followed up until December 31, 2007. The person-year approach was used to estimate standardized incidence ratios (SIRs) and excess absolute risks (EARs) of metachronous SPC. Multivariate Poisson regression models were then used to model SIRs and EARs separately by gender, adjusting for age, year of diagnosis, follow-up and first cancer site.
Among the 289,967 followed-up patients with a first primary cancer, 21,226 developed a SPC. The SIR was of 1.36 (95% CI, 1.35-1.38) and the EAR was of 39.4 excess cancers per 10,000 person-years (95% CI, 37.4-41.3). Among male and female patients, multivariate analyses showed that age, year of diagnosis, follow-up and first cancer site were often independently associated with SIRs and EARs. Moreover, the EAR of SPC remained elevated during patient follow-up.
French cancer survivors face a dramatically increased risk of SPC which is probably related to the high rate of tobacco and alcohol consumption in France. Multivariate modeling of SPC risk will facilitate the construction of a tailored prediction tool to optimize SPC prevention and early detection strategies.
BMC Cancer 02/2014; 14(1):94. DOI:10.1186/1471-2407-14-94 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155-280]; B-CRC n = 21, 318[166-480]; B-RT n = 37, 149[130-214]; RS-CT n = 11, 245[211-na]; RS-CRC n = 18, 372[349-593]; RS-RT n = 39, 269[218-343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.