The Economic Cost of Thyroid Cancer in France and the Corresponding Share Associated With Treatment of Overdiagnosed Cases.

OBJECTIVES: Thyroid cancer incidence in France has increased rapidly in recent decades. Most of this increase has been attributed to overdiagnosis, the major consequence of which is overtreatment. We aimed to estimate the cost of thyroid cancer management in France and the corresponding cost proportion attributable to the treatment of overdiagnosed cases. METHODS: Multiple data sources were integrated: the mean cost per patient with thyroid cancer was estimated by using the Echantillon Généraliste des Bénéficiaires data set; thyroid cancer cases attributable to overdiagnosis were estimated for 21 departments using data from the French network of cancer registries and extrapolated to the whole country; medical records from 6 departments were used to refine the diagnosis and care pathway. RESULTS: Between 2011 and 2015, 33 911 women and 10 846 men in France were estimated to be diagnosed of thyroid cancer, with mean cost per capita of €6248. Among those treated, 8114 to 14 925 women and 1465 to 3626 men were due to overdiagnosis. The total cost of thyroid cancer patient management was €203.5 million (€154.3 million for women and €49.3 million for men), of which between €59.9 million (or 29.4% of the total cost, lower bound) and €115.9 million (or 56.9% of the total cost, upper bound) attributable to treatment of overdiagnosed cases. CONCLUSIONS: The management of thyroid cancer represents not only a relevant clinical and public health problem in France but also a potentially important economic burden. Overdiagnosis and corresponding associated treatments play an important role on the total costs of thyroid cancer management.

Evolution of breast cancer incidence in young women in a French registry from 1990 to 2018: Towards a change in screening strategy?

BACKGROUND: The worldwide incidence of invasive breast cancer in women is increasing according to several studies. This increase in incidence seems to be higher in young women (< 40 years). However, the reasons for this trend are poorly understood. This article aims to provide the most recent estimates of this trend and assess whether there is indeed an increase in the incidence of breast cancer among young women to strengthen prevention campaigns. METHODS: We collected data from the Isere cancer registry in France of all invasive breast cancers from January 1990 to December 2018. The standardized incidence rate was calculated for four age groups (< 40 years, 40-49 years, 50-74 years, ≥ 75 years) for this period. The 10-year relative survival was evaluated for each age group age for two periods (1990-1999 and 2000-2008). From 2011 to 2013, we analyzed the incidence and 5-year relative survival by tumor subtype (triple negative, luminal, HER2 amplified) for each age group. RESULTS: A total of 23,703 cases were selected, including 1343 young women (< 40 years). The incidence of invasive breast cancer increased annually by 0,8% (95% CI 0,7; 1) in all age groups combined from 1990 to 2018. The highest incidence increase is found among young women, by 2,1% annually (95% CI 1,3; 2,8). Regarding tumor subtypes from 2011 to 2018, the incidence of triple negatives increases higher in young women (+ 1,4% by year, 95% CI - 8,2; 11) and those over 75 years (+ 4% by year, 95% CI - 5,1; 13,2), but the results are not statistically significant. 10-year relative survival in young women increased from 74,6% (95% CI 69,6; 78,9) to 78,3%(95% CI 73,7; 82,1) between 1990-1999 and 2000-2008, respectively. Five-year relative survival is better in young women among triple negative and HER2 amplified. CONCLUSION: Our study confirms the current trend of increasing the incidence of breast cancer in young women, associated with improved survival very likely attributable to earlier diagnosis due to increased awareness, and improvements in treatment. A better individualized risk-based screening strategy is needed for these patients. Additional studies will be needed to more accurately assess the risk of developing breast cancer and improve diagnostic performance.

Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization.

BACKGROUND: At the diagnosis of hepatocellular carcinoma (HCC), more than 90% of HCC patients present cirrhosis, a clinical condition often associated to malnutrition. Sarcopenia is an indirect marker of malnutrition assessable on computed tomography (CT). AIM: To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial (chemo)-embolization. METHODS: Patients with HCC treated by a first session of trans-arterial (chemo)embolization and an available CT scan before treatment were included. Sarcopenia was assessed using skeletal muscle index at baseline and at the first radiological assessment. Radiological response was recorded after the first session of treatment using mRECIST. RESULTS: Of 225 patients treated by trans-arterial bland embolization (n = 71) or trans-arterial chemoembolization (n = 154) for HCC between 2007 and 2013, Barcelona Clinic of Liver Cancer stage was A, B, and C in 27.5%, 55%, and 16.8% of cases, respectively. Sarcopenia was present in 57.7% of the patients. Patients with sarcopenia presented a higher rate of progressive disease (19% vs 8%, P = 0.0236), a shorter progression-free survival (8.3 vs 13.2 mo, P = 0.0035), and a shorter median overall survival (19.4 mo vs 35.5 mo, P = 0.0149) compared with non-sarcopenic patients. Finally, patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis (P = 0.0004). CONCLUSION: Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial (chemo)-embolization for HCC.

Biliary cytology: A diagnostic tree for adenocarcinoma based on a cohort of 135 patients with endoscopic retrograde cholangiopancreatography for stenosis of the extrahepatic bile duct.

BACKGROUND: The diagnosis of well-differentiated adenocarcinoma on bile aspiration is a well-known challenge. This study was aimed at improving the diagnostic performance and providing a biliary cytology learning atlas. METHODS: This single-center, retrospective study included 135 cases of informative biliary samples collected between 2009 and 2018 that were classified as benign, atypical, or malignant. A double assessment was performed by a novice and a cytopathologist experienced in biliary cytology to establish the specificities, sensitivities, and inter- and intraobserver κ index agreements of 24 cytological criteria, which were illustrated in a learning atlas. RESULTS: A multivariate logistic regression was used to assess whether the most specific and reproducible criteria were associated with malignancy. A scoring system was statistically determined: 6 points were attributed in the presence of a 3-dimensional (3D) cluster, anisonucleosis, and a nuclear to cytoplasmic (N:C) ratio > 0.5, whereas 4 points were given in the presence of an enhanced nuclear membrane. A score higher than 10 points resulted in a malignancy diagnosis with 96% sensitivity and 97% specificity. CONCLUSIONS: A diagnostic tree of malignancy based on 4 criteria, together with a multidisciplinary approach, allows the diagnosis of adenocarcinoma with a specificity of 100% and a sensitivity of 88% or 72% depending on the presence of a single malignant cell or the presence of 3 combined criteria (a 3D cluster, anisonucleosis, and an N:C ratio > 0.5). It comes with a learning atlas useful for cytopathologist training and accuracy in this uncommon cytology.

Cutaneous adverse events in children treated with vemurafenib for refractory BRAFV600E mutated Langerhans cell histiocytosis.

BACKGROUND: The somatic BRAFV600E mutation occurs in 38-64% of pediatric cases of Langerhans cell histiocytosis (LCH). Vemurafenib (VMF), a BRAF inhibitor, was approved for refractory BRAFV600E mutated LCH. In adults, VMF causes frequent cutaneous adverse events (CAE) including skin tumors (squamous cell carcinomas, melanomas), but little is known in children. The objective of this study was to evaluate the frequency, clinical spectrum, and severity of CAEs in children treated with VMF for LCH. In addition, a correlation between CAE occurrence and VMF dose, residual plasma levels (RPLs), and efficacy was searched for. PROCEDURE: Multicentric retrospective observational study including patients <18 years treated with VMF alone for refractory BRAFV600E mutated LCH in 13 countries between October 1, 2013 and December 31, 2018. RESULTS: Fifty-seven patients: 56% female, median age 2.1 years (0.2-14.6), median treatment duration 4.1 months (1.4-29.7). Forty-one patients (72%) had at least one CAE: photosensitivity (40%), keratosis pilaris (32%), rash (26%), xerosis (21%), and neutrophilic panniculitis (16%). No skin tumor was observed. Five percent of CAEs were grade 3. None were grade 4 or led to permanent VMF discontinuation. Dose reduction was necessary for 12% of patients, temporary treatment discontinuation for 16%, none leading to loss of efficacy. VMF dose, median RPL, and efficacy were not correlated with CAE occurrence. CONCLUSIONS: At doses used for pediatric LCH, CAEs are frequent but rarely severe and have little impact on the continuation of treatment when managed appropriately. Regular dermatological follow-up is essential to manage CAEs and screen for possible induced skin tumors.

Comparison of Trans-Arterial Chemoembolization and Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis.

No definitive conclusion could be reached about the role of chemotherapy in adjunction of embolization in the treatment of hepatocellular carcinoma (HCC). We aim to compare radiological response, toxicity and long-term outcomes of patients with hepatocellular carcinoma (HCC) treated by trans-arterial bland embolization (TAE) versus trans-arterial chemoembolization (TACE). We retrospectively included 265 patients with HCC treated by a first session of TACE or TAE in two centers. Clinical and biological features were recorded before the treatment and radiological response was assessed after the first treatment using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Correlation between the treatment and overall, progression-free and transplantation-free survival was performed after adjustment using a propensity score matching: 86 patients were treated by bland embolization and 179 patients by TACE, including 44 patients with drug-eluting beads and 135 with lipiodol TACE, 89.8% of patients were male with a median age of 65 years old. Cirrhosis was present in 90.9% of patients with a Child Pugh score A in 84% of cases. After adjustment, no difference in the rate of AE, including liver failure, was observed between the two treatments. TACE was associated with a significant increase in complete radiological response (odds ratio (OR) = 8.5 (95% confidence interval (CI): 2.8-25.4)) but not in the overall response rate (OR = 2.2 (95% CI = 0.8-5.8)). No difference in terms of overall survival (p = 0.3905), progression-free survival (p = 0.4478) and transplantation-free survival (p = 0.9020) was observed between TACE and TAE. TACE was associated with a higher rate of complete radiological response but without any impact on overall radiological response, progression-free survival and overall survival compared to TAE.

Association of Mammography Screening With a Reduction in Breast Cancer Mortality: A Modeling Study Using Population-Based Data From 2 French Departments.

Meta-analyses of randomized controlled trials that started from 1963 to 1991 reported a decrease of breast cancer mortality, associated with mammography screening. However, the effectiveness of population-based screening programs conducted currently might have changed due to the higher effectiveness of treatments for late-stage cancers and the better diagnostic performance of mammography. The main objective of this study was to predict the reduction of breast cancer mortality associated with mammography screening in the current French setting. We compared breast cancer mortality in 2 simulated cohorts of women, which differed from each other solely in a 70% biennial participation in screening from 50 to 74 years old. The microsimulation model used for predictions was calibrated with incidence rates of breast cancer according to stage that were observed in Isère and Loire-Atlantique departments, France, in 2007-2013. The model predicted a decrease of breast cancer mortality associated with mammography screening of 18% (95% CI: 5, 31) and 17% (95% CI: 3, 29) for models calibrated with data from Isère and Loire-Atlantique departments, respectively. Our results highlight the interest in biennial mammography screening from ages 50 to 74 years old to decrease breast cancer mortality in the current setting, despite improvements in treatment effectiveness.

External evaluation of the Briganti nomogram to predict lymph node metastases in intermediate-risk prostate cancer patients.

PURPOSE: The Briganti nomogram can be used with a threshold of 5% to decide when to offer lymph node dissection during radical prostatectomy. The objective of the study was to assess the accuracy of the Briganti nomogram on intermediate-risk prostate cancer patients managed in a single academic department. METHODS: We retrospectively reviewed the files of all patients managed by radical prostatectomy (RP) and bilateral pelvic lymph node dissection (BPLND) in our center between 2005 and 2017. The overall accuracy of the model in predicting metastatic lymph node disease was quantified by the construction of a receiver-operator characteristic (ROC) curve. A calibration plot was drawn to represent the relationship between the predicted and observed frequencies. RESULTS: We included 285 patients, among whom 175 (61.4%) were classified as intermediate risk as defined by D'Amico. The median follow-up was 60 (34-93) months. Twenty-seven patients (9.5%) were diagnosed with lymph node metastases. The median number of lymph nodes removed was 10 (7-14). The mean Briganti score was 19.3% in patients with lymph node involvement (LNI) and 6.3% in patients without LNI. Focusing on intermediate-risk patients, 91(52%) and 84 (48%) had a Briganti score < 5% and ≥ 5%, respectively, among whom 6 (6.6%) and 7(8.3%) had lymph node metastases. The accuracy of the score was low for intermediate risk patients with an area under the curve (AUC) of 53.1% (95% CI 0.45-0.61). CONCLUSION: The Briganti nomogram in our retrospective cohort showed low accuracy for the prediction of lymph node involvement in an intermediate-risk prostate cancer population.

Circulating IL-13 Is Associated with De Novo Development of HCC in HCV-Infected Patients Responding to Direct-Acting Antivirals.

Direct-acting antivirals (DAAs) are highly effective in targeting hepatitis C virus (HCV) infections, but the incidence of HCV-related hepatocellular carcinoma (HCC) remains still high. In this study, we investigated a cohort of HCV-infected patients treated with DAAs who were followed up for 4 years after sustained virological response (SVR) achievement. Patients who developed de novo HCC following DAA treatment were compared to matched controls who did not develop HCC. These control patients were selected based on DAA treatment, sex, age, fibrosis status, and platelet counts. We evaluated serum levels of 30 immune mediators before, during, at the end of, and three months after DAA treatment using Luminex technology. We identified the immune factors associated with de novo HCC occurrence following DAA treatment. Specifically, interleukin (IL)-4 and IL-13 levels were significantly higher before start of the DAA treatment in the serum of patients who later developed HCC than in controls and stayed higher at each subsequent time point. Least absolute shrinkage and selection operator (LASSO) regression revealed IL-13 as the only strong factor associated with HCC development in this cohort of HCV patients. The difference was observed already at baseline of DAA treatment, which confirms the existence of a specific immune profile in these patients who later develop HCC.

Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma.

BACKGROUND: Liver cancer is the fifth most common cancer and the second cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the best treatment of intermediate hepatocellular carcinoma (HCC). Doxorubicin is the most commonly used drug despite a low level of evidence. AIM: To compare the objective response rate of idarubicin-based TACE (Ida-TACE) against doxorubicin-based TACE (Dox-TACE) in intermediate stage HCC. METHODS: Between January 2012 and December 2014, all patients treated with TACE at our academic hospital were screened. Inclusion criteria were patients with Child-Pugh score A or B, a performance status below or equal to 1, and no prior TACE. Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin. Each patient treated with idarubicin was matched with two doxorubicin-treated patients. The TACE response was assessed by independent radiologists according to the mRECIST criteria. RESULTS: Sixty patients were treated with doxorubicin and thirty with idarubicin. There were 93% and 87% of cirrhotic patients and 87% and 70% of Child-Pugh A in the doxorubicin and idarubicin groups, respectively. The median number of HCC per patient was two in both groups with 31% and 26% of single nodules in doxorubicin and idarubicin groups, respectively. Objective response rate after first TACE was 76.7% and 73.3% (P = 0.797) with 41.7% and 40.0% complete response in doxorubicin and idarubicin groups, respectively. Progression-free survival was 7.7 mo in both groups, and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups, respectively. Safety profiles were similar in both groups, with grade 3-4 adverse events in 35% of Dox-TACE and 43% of Ida-TACEs. CONCLUSION: Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety. Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.

A twelve-year study of the prevalence, risk factors and characteristics of interval colorectal cancers after negative colonoscopy.

INTRODUCTION: The objective of our study was to describe and analyse the Post-Colonoscopy Colorectal Cancers (PCCRCs) and endoscopist performance-related risk factors in the Isère regional screening programme. METHOD: This was a population-based retrospective cohort study between 2002-2013, where Post-Colonoscopy Colorectal Cancers (PCCRCs) were defined as colorectal adenocarcinoma diagnosed between six and sixty months post-colonoscopy following a positive gFOBT. We analysed the endoscopist performance-related risk factors of the 62 gastroenterologists who had carried out at least 30 colonoscopies during this period. RESULTS: During the period reviewed, there were 10,557 negative colonoscopies performed. Fifteen post-colonoscopy colorectal cancers were diagnosed from 2002-2013 with an average patient age of 67.1 years. Men comprised 73% of the cases and 53% of all the cases were found in the distal colon. These 15 cases comprised 1.1% of all Colorectal Cancers (CRCs) diagnosed in the screening programme, with an incidence rate of 0.42 (0.21-0.77) per 1,000 person-years. The aetiological breakdown was as follows: 47% related to missed cancers, 27% were new cancers, 20% were failed biopsy detection, and 6% related to incomplete removal. The Adenoma Detection Rate (ADR) among gastroenterologists was an average of 30%, but large heterogeneity was present within this number, ranging from 11% to 49%. CONCLUSION: The post-colonoscopy colorectal cancer prevalence and incident rate were low relative to the literature. However, significant heterogeneity was present in the adenoma detection rate. Decreasing this heterogeneity by establishing a national benchmark, regular performance feedback and training modules should homogenise adenoma detection rates and decrease the number of interval cancers in the region.

Incidence of prostate cancer and net survival by grade in a geriatric population: A population-based study in a French administrative entity from 1991 to 2013.

BACKGROUND: Prostate cancer is the leading type of cancer among men in more developed countries. Incidence trends and survival rates could differ by age groups considering potential differences in the frequency of PSA testing, types of cancers and medical management. Our objective was to compare incidence trends and survival rates of prostate cancer between men aged ≥75 and 60-74 years. METHOD: We analyzed data from a population-based cancer registry in Isère, France. All men aged ≥60 years diagnosed with an incident prostate cancer during the 1991-2013 period were included. Incidence and mortality rates were computed as well as net survival rates. RESULTS: In 2013, observed incidence rates were 557.6 and 568.7 per 100,000 for men aged 60-74 and ≥75, respectively, with high grades cancers more frequent among elderly men. The incidence and mortality trends among men aged ≥75 included a period of stability followed by a decreasing trend from 2003, whereas a peak of incidence was observed in 2005 for men aged 60-74. For both age groups, net survival rates increased with period of diagnosis and 8-year net survival remained higher than 70% for cases diagnosed in the 2000-2004 period. Lower survival rate of 51% (95%CI: 42%; 60%) was observed for high grades cancers diagnosed among men aged 75-84 in 2000-2004. CONCLUSION: The epidemiology of prostate cancers among men aged ≥75 include a decrease of incidence and mortality rates from 2003, an important proportion of high grade cancers and a relatively good prognosis except for high grade cancers.

Evolution of EBV seroprevalence and primary infection age in a French hospital and a city laboratory network, 2000-2016.

BACKGROUND: According to rare studies, the age at EBV primary infection (PI) has recently risen in some developed countries. A later age at infection is generally considered a risk factor for severe EBV PI, although few studies exist on this subject. Our investigation aimed to determine whether EBV seroprevalence and EBV PI epidemiology have evolved in France, and to what extent age and infection intensity (regarding biological parameters) are correlated. METHODS AND FINDINGS: We conducted a retrospective study of the following EBV serological tests databases: tests carried out at Grenoble University Hospital (2000-2016) (n = 53,553); and tests carried out by a network of city laboratories in Grenoble area (2008-2015) (n = 27,485). The hospital population showed a continuous, significant decrease in EBV seroprevalence over the studied period for patients aged 20 and over (p<0.01). The seroprevalence also decreased for different age classes (<10, 15-19, 20-30, and 30-40 years old) over the periods 2001-2005, 2006-2010, and 2011-2015. Consistently, the age at PI was significantly higher in the years 2008-2015 than in the years 2001-2007 (15.6±12.0 vs. 13.7±11.0; p = 0.03). The city laboratory population showed the same trend of decreasing seroprevalence (p = 0.06); no significant variations in age at PI were observed. The age at PI was positively correlated with ASAT, ALAT, γGT, and bilirubin blood levels (p<0.01) and negatively correlated with platelet counts (p<0.05). CONCLUSION: In the last 15 years, the age at EBV PI has increased, whereas seroprevalence has decreased. Moreover, our findings confirm the positive correlation between age and biological abnormalities. Taken together, these results suggest that the incidence of severe EBV PI will increase in the future.

Overdiagnosis and overtreatment associated with breast cancer mammography screening: A simulation study with calibration to population-based data.

OBJECTIVES: The magnitude of overdiagnosis of breast cancer associated with mammography screening remains controversial because of methodological issues. The objective of this study was to quantify overdiagnosis and overtreatment associated with a population-based screening programme, taking into account lead time and uncertainty concerning baseline incidence of breast cancers. MATERIAL AND METHODS: A simulation model was developed to replicate incidence and detection rates of breast cancer observed in the Isère Département, France. The parameters of the model were estimated using an approximate Bayesian computation method. RESULTS: For women aged 50-74 years during the 2007-2010 period, overdiagnosis of non-progressive breast cancers accounted for 17.0% (95% credibility interval (CI): 2.5%-35.5%) of all in situ cancers diagnosed, 5.5% (95% CI: 0.8%-9.8%) of all invasive cancers diagnosed, and 20.3% (95% CI: 3.0%-38.9%) of in situ and 13.0% (95% CI: 2.2%-23.3%) of invasive screen detected breast cancers. The estimates of overdiagnosis due to competitive causes of death were 1.0% (95% CI: 0.2%-%1.7) and 1.1% (95% CI: 0.6%-1.7%) for all in situ and invasive cancers diagnosed, respectively, and 1.3% (95% CI: 0.2%-2.0%) and 2.6% (95% CI: 1.4%-4.0%) of all in situ and invasive screen detected breast cancers, respectively. Among 1000 screen-detected cancers in 2010, 155 (95% CI: 27-284), 134 (95% CI: 10-242) and 140 (95% CI: 25-254) women underwent breast conserving surgery, lymph node dissection and radiation therapy for overdiagnosed cancers, respectively. CONCLUSION: Our estimates of overdiagnosis should be balanced against the reduction of breast cancer mortality to assess the value of breast cancer screening programme.

Experience feedback committee in emergency medicine: a tool for security management.

OBJECTIVE: Emergency departments are high-risk structures. The objective was to analyse the functioning of an experience feedback committee (EFC), a security management tool for the analysis of incidents in a medical department. METHODS: We conducted a descriptive study based on the analysis of the written documents produced by the EFC between November 2009 and May 2012. We performed a double analysis of all incident reports, meeting minutes and analysis reports. RESULTS: During the study period, there were 22 meetings attended by 15 professionals. 471 reported incidents were transmitted to the EFC. Most of them (95%) had no consequence for the patients. Only one reported incident led to the patient's death. 12 incidents were analysed thoroughly and the committee decided to set up 14 corrective actions, including eight guideline writing actions, two staff trainings, two resource materials provisions and two organisational changes. CONCLUSIONS: The staff took part actively in the EFC. Following the analysis of incidents, the EFC was able to set up actions at the departmental level. Thus, an EFC seems to be an appropriate security management tool for an emergency department.

Sensitivity of a colorectal cancer screening program based on a guaiac test: a population-based study.

BACKGROUND: The main objective of this study was to estimate the sensitivity of a colorectal cancer-screening program based on a guaiac fecal occult blood (FOB) test. The secondary objective was to determine whether the sensitivity varied by sex and if the difference between males and females could be explained by differences in age group at the time of the test, round of screening, how the test was provided to the participant, tumor location, and the presence of theoretical screening program exclusion criteria. METHODS: For the 2002-2006 period, we retrospectively analyzed data from the organized colorectal screening program in Isère, France, which was designed for asymptomatic individuals aged 50-74. Sensitivity was assessed considering the number of interval cancers diagnosed in the 2 years following the test. A logistical regression analysis was done to evaluate the factors associated with the sensitivity of the screening program. RESULTS: A total of 506 participants were included in the analysis. The overall sensitivity of the screening program was 48.4%, being 58.3% for males and 32.5% for females. In multivariate analysis, sensitivity for males was still higher than for females (OR=2.1 [95% CI, 1.4-3.4]) after adjusting for age group, presence of exclusion criteria, the way the test was given, the round of participation, and the tumor location. A total of 183 (36.2%) study subjects presented with at least one exclusion criterion for the screening program. CONCLUSION: The sensitivity of the colorectal cancer-screening program based on a guaiac test was insufficient, being higher for males than for females. This difference in sensitivity was not entirely explained by differences in age, characteristics of screening participation, and tumor location.

Determinants of participation in organized colorectal cancer screening in Isère (France).

BACKGROUND AND AIMS: In France, participation in organized colorectal cancer screening remains low. The objective of this study was to identify the determinants of participation in colorectal cancer screening in Isère, a French administrative entity. METHODS: This study examined the target population invited for screening between 2007 and 2008 in Isère. The statistical analysis method was based on a two-level logistic regression model: the first was the individual level relative to the individuals invited for screening and the second was an aggregate level corresponding to the socioeconomic level of an invited person's residence area (IRIS: "Ilot regroupé pour l'Information Statistique"; Regrouped statistical information block). The evaluation of the socioeconomic level was based on the Townsend deprivation. RESULTS: Participation varied depending on sex, age, and health insurance plan. The people residing in the least deprived IRISes participated more than individuals residing in the most deprived IRISes. The multilevel analysis showed a 24% difference in participation between the least and the most deprived IRISes. CONCLUSIONS: The use of socioeconomic data on the IRIS geographical unit has identified, socially and geographically, the populations that participate the least, although this reflects "mean" behaviors. These results could be used to set up targeted actions to encourage participation in these populations.

Overdiagnosis from non-progressive cancer detected by screening mammography: stochastic simulation study with calibration to population based registry data.

OBJECTIVE: To quantify the magnitude of overdiagnosis from non-progressive disease detected by screening mammography, after adjustment for the potential for lead time bias, secular trend in the underlying risk of breast cancer, and opportunistic screening. DESIGN: Approximate bayesian computation analysis with a stochastic simulation model designed to replicate standardised incidence rates of breast cancer. The model components included the lifetime probability of breast cancer, the natural course of breast cancer, and participation in organised and opportunistic mammography screening. SETTING: Isère, a French administrative region with nearly 1.2 million inhabitants. PARTICIPANTS: All women living in Isère and aged 50-69 during 1991-2006. MAIN OUTCOME MEASURES: Overdiagnosis, defined as the proportion of non-progressive cancers among all cases of invasive cancer and carcinoma in situ detected 1991-2006. RESULTS: In 1991-2006, overdiagnosis from non-progressive disease accounted for 1.5% of all cases of invasive cancer (95% credibility interval 0.3% to 2.9%) and 28.0% of all cases of carcinoma in situ (2.2% to 59.8%) detected either clinically or by screening mammography in Isère. When analysis was restricted to the cancers detected by screening mammography only, the estimates of overdiagnosis were 3.3% (0.7% to 6.5%) and 31.9% (2.9% to 62.3%) for invasive cancer and carcinomas in situ, respectively. CONCLUSION: Overdiagnosis from the detection of non-progressive disease by screening mammography was limited in 1991-2006 in Isère. Because carcinoma in situ accounted for less than 15% of all incident breast cancer cases, its contribution to overdiagnosis was relatively limited and imprecise.

Association of diagnostic work-up with subsequent attendance in a breast cancer screening program for false-positive cases.

The objective of this study is to determine whether the likelihood of returning for routine breast cancer screening differed for false-positive cases depending on the diagnostic work-up. Using the original data from a French population-based breast cancer screening program, we compared the attendance rates at the subsequent round of screening for 16,946 and 1,127 participants who received negative (i.e., American College of Radiology, ACR, categories 1-2) and false-positive mammograms, respectively. False-positive mammograms were categorized ACR 0 (i.e., warranting additional imaging evaluation), 3 (i.e., warranting clinical and imaging follow-up), and 4-5 (i.e., warranting biopsy). We estimated the odds ratios of attendance at subsequent screening round using logistic regression, adjusting for age and history of previous mammography. The attendance rates at the subsequent screening round were 80.6% for women who received negative mammograms versus 69.6, 74.3, and 70.1% for women who received false-positive mammograms warranting additional imaging evaluation, clinical and imaging follow-up, or biopsy, respectively. In comparison to women who received negative mammograms, the corresponding adjusted odds ratios of returning for routine screening were 0.6 [95% confidence interval (CI) 0.4-0.8], 0.8 (95% CI 0.6-0.9), and 0.6 (95% CI 0.4-0.8). No significant differences were found in odds ratios of attendance across ACR categories among women who received false-positive mammograms. Similar figures were observed for attending at least one of the two subsequent screening rounds. In conclusion, in comparison to women with normal or benign findings on index mammograms, false-positive cases warranting additional imaging evaluation, clinical and imaging follow-up, or biopsy had uniformly decreased odds of attending subsequent routine screening rounds.

Incidence of second cancer within 5 years of diagnosis of a breast, prostate or colorectal cancer: a population-based study.

The objective of this study was to evaluate the risk for cancer patients of developing a new primary invasive cancer. Using data from a French Cancer Registry, we included 14,353 cancer patients (breast, colorectal or prostate cancer) diagnosed between 1989 and 1997. Observed second cancers occurring during the first 5 years after the first cancer were compared with the expected number, based on primary cancer incidence rate, by the standardized incidence ratio (SIR). Breast cancer patients had significantly elevated SIR for contralateral breast cancer (SIR=1.7), kidney cancer (SIR=3.5) and myeloid leukaemia (SIR=8.3). Patients diagnosed with colorectal cancer had significantly elevated risk for small intestine (SIR=10.7) and colorectal cancer (SIR=1.6). Young age at diagnosis of breast and colorectal cancers was associated with risk of a second cancer. After prostate cancer, men had no greater risk of cancer, except for kidney cancer. Our results help to direct attention to regions especially vulnerable to secondary cancers after primary breast or colorectal cancer.