Epidemiology of Merkel cell carcinoma. A population-based study from 1985 to 2013, in northeastern of France.

Merkel Cell Carcinoma (MCC) is an aggressive skin cancer with an increasing incidence. Population-based epidemiologic data about MCC in France are rare. Our study aims to describe the epidemiology of MCC in Bas-Rhin, Northeastern of France, between 1985 and 2013. Data were collected from the Bas-Rhin Cancer Registry. We measured age-adjusted incidence rates (per 100,000 person-years) and effect of age, sex and period of diagnosis on survival. The world age-standardized incidence rate was 0.17 and it quadrupled between 1985 and 2013. Cases (n = 111) occurred mostly in women (60%) and in persons ≥70 years of age (74%). Incidence rates was close for men (0.18) and women (0.16) and was 25-time higher in people ≥70 years of age but incidence rate similarly increased between 1985 and 2013 in persons older and younger than 70 years. Net 5-year survival was 48.5%; female sex and younger age were positive predictors of survival. Given the low number of cases, incidence and survival data should be interpreted with caution. Incidence of MCC in Bas-Rhin quadrupled between 1985 and 2013. The highest incidence rate was observed in people ≥70 years. Better survival was associated with female sex and younger age. We hypothesize that MCC will still increase and be diagnosed in increasingly younger patients in next generations.

Conformity to Clinical Practice Guidelines at Initial Management in Adult Soft Tissue and Visceral Tumors since the Implementation of the NetSarc Network in Eastern France.

BACKGROUND: Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management. MATERIALS AND METHODS: Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed. RESULTS: A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center. CONCLUSION: Initial diagnostic management requires improvement, especially outside of specialized centers. IMPLICATIONS FOR PRACTICE: This article supports the essential need to refer patients with soft tissue tumors to specialized centers to improve the management of sarcomas beginning at the diagnostic phase. Indeed, the reported data were very similar to those already described at the national level of the NetSarc network and indicate the necessity to keep raising awareness about this simple issue: early referral to reference centers will save lives.

Incidence of solitary pulmonary nodules in Northeastern France: a population-based study in five regions.

BACKGROUND: The discovery of a solitary pulmonary nodule (SPN) on a chest imaging exam is of major clinical concern. However, the incidence rates of SPNs in a general population have not been estimated. The objective of this study was to provide incidence estimates of SPNs in a general population in 5 northeastern regions of France. METHODS: This population-based study was undertaken in 5 regions of northeastern France in May 2002-March 2003 and May 2004-June 2005. SPNs were identified by chest CT reports collected from all radiology centres in the study area by trained readers using a standardised procedure. All reports for patients at least 18 years old, without a previous history of cancer and showing an SPN between 1 and 3 cm, were included. RESULTS: A total of 11,705 and 20,075 chest CT reports were collected for the 2002-2003 and 2004-2005 periods, respectively. Among them, 154 and 297 reports showing a SPN were included, respectively for each period. The age-standardised incidence rate (IR) was 10.2 per 100,000 person-years (95% confidence interval 8.5-11.9) for 2002-2003 and 12.6 (11.0-14.2) for 2004-2005. From 2002 to 2005, the age-standardised IR evolved for men from 16.4 (13.2-19.6) to 17.7 (15.0-20.4) and for women from 4.9 (3.2-6.6) to 8.2 (6.4-10.0). In multivariate Poisson regression analysis, gender, age, region and period were significantly associated with incidence variation. CONCLUSIONS: This study provides reference incidence rates of SPN in France. Incidence was higher for men than women, increased with age for both gender and with time for women. Trends in smoking prevalence and improvement in radiological equipment may be related to incidence variations.

Trends in the risk of second primary cancer among bladder cancer survivors: a population-based cohort of 10 047 patients.

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 10 French population-based cancer registries were used to establish a cohort of 10 047 patients diagnosed with a first invasive (≥T1) BCa between 1989 and 2004 and followed up until 2007. An SPC was defined as the first subsequent primary cancer occurring at least 2 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. RESULTS: The risk of new malignancy among BCa survivors was 60% higher than in the general population (SIR 1.60, 95% confidence interval [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 for gender, age at diagnosis and follow-up, a significant increase in the risk of SPC of the lung was observed over the calendar year of BCa diagnosis (P for linear trend 0.010), with an SIR increasing by 3.7% for each year (95% CI 0.9-6.6%); however, no particular trend was observed regarding the risk of SPC of the head and neck (P = 0.596) or the prostate (P = 0.518). CONCLUSIONS: As the risk of SPC of the lung increased between 1989 and 2004, this study contributes more evidence to support the promotion of tobacco smoking cessation interventions among patients with BCa.

Risk of second primary cancer after a first potentially-human papillomavirus-related cancer: A population-based study.

Human papillomaviruses (HPV) are involved in the development of anogenital and head and neck cancers. The purpose of this study was to assess the risk of developing a second primary cancer (SPC) after a first potentially-HPV-related cancer, and to analyze the sites where SPCs most frequently occurred in these patients. All patients with a first cancer diagnosed between 1989 and 2004, as recorded by 10 French cancer registries, were followed up until December 31, 2007. Only invasive potentially-HPV-related cancers (namely, cervical, vagina, vulva, anal canal, penile, oropharynx, tongue and tonsil) were included. Standardized Incidence Ratios (SIRs) were calculated to assess the risk of SPC. A multivariate Poisson regression model was used to model SIRs separately by gender, adjusted for the characteristics of the first cancer. 10,127 patients presented a first potentially-HPV-related cancer. The overall SIR was 2.48 (95% CI, 2.34-2.63). The SIR was 3.59 (95% CI, 3.33-3.86) and 1.61 (95% CI, 1.46-1.78) in men and women respectively. The relative risk of potentially-HPV-related SPC was high among these patients (SIR=13.74; 95% CI, 8.80-20.45 and 6.78; 95% CI, 4.61-9.63 for men and women, respectively). Women diagnosed in the most recent period (2000-2004) showed a 40% increase of their relative risk of SPC as compared with women diagnosed between 1989 and 1994 (ratio of SIRs=1.40; 95% CI, 1.06-1.85). HPV cancer survivors face an increased risk of SPC, especially second cancer. Clinicians may consider this increased risk of developing HPV-related SPC during follow-up to improve subsequent cancer prevention in these patients.

The effect of patient characteristics on second primary cancer risk in France.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cross-cultural French adaptation and validation of the Impact On Family Scale (IOFS).

BACKGROUND: The IOFS (Impact On Family Scale) questionnaire is a useful instrument to assess the impact of chronic childhood conditions on general family quality of life. As this instrument was not validated in French, we proposed to translate, adapt and validate the IOFS questionnaire for clinical and research use in French-speaking populations. FINDINGS: The sample studied comprised French-speaking parents with a child presenting a cleft lip or cleft lip and palate, aged 6 to 12 years and treated in the University Hospital of Strasbourg, France. The 15-item version of the IOFS was translated into French and then sent to the parents by post. The structure of the measure was studied using Exploratory Factor Analysis (EFA), internal consistency was assessed using Cronbach's alpha coefficient and test-retest reliability was studied by calculating the Intraclass Correlation Coefficient (ICC). CONCLUSIONS: The French version of the IOFS questionnaire exhibited very good psychometric properties. For practitioners, this instrument will facilitate the assessment of the impact of chronic childhood conditions on quality of life among French-speaking families.

Use of psychotropic drugs, systemic antihistamines and medications for cough in 6-year-old children: a survey in the Bas-Rhin Region, France.

PURPOSE: The use of drugs in France is among the highest in developed countries. Among them, psychotropic medication in children has always been a matter of concern. Furthermore, on the basis of concerns about safety and efficacy, international authorities have either advised against the use of cough and cold medication or considered such an action. This survey aims to assess the prevalence of use of psychotropic drugs, antihistamines and medications for cough as well as parents' knowledge about the drugs used in 2009. METHODS: The study is based on a representative sample of 6-year-old children who were in kindergarten in 2009. School physicians asked their parents to answer a standardized questionnaire. Data were collected about the child, his or her family, and the consumption of psychotropic drugs, antihistamines, and medications for cough in the past 12 months. The Anatomical Therapeutic Chemical (ATC) classification system was used to classify the drugs used. RESULTS: The data from 5707 children were analyzed. The proportion of children who consumed at least one psychotropic drug was 0.68% (ATC code N). Antihistamines for systemic use were by far the most frequently consumed drugs (ATC code R06), with a prevalence of 17.54%. The great majority of antihistamines for systemic use were meant to treat cough, not insomnia or agitation. CONCLUSION: The use of psychotropic drugs was low in 2009 in the French region of Bas-Rhin. The promotion of alternatives to antihistamines for systemic use to treat cough should nevertheless be strengthened.

Slow-release oral morphine for opioid maintenance treatment: a systematic review.

This review article summarizes the results of all available clinical trials considering the use of slow-release oral morphine (SROM) for opioid maintenance treatment (OMT). All studies published up to October 2010 and assessing SROM for OMT in adult patients are included. Three independent reviewers assessed the selected articles using a standardized checklist. Study design, study length and number of subjects included were recorded. Data about retention rate (proportion of participants remaining under maintenance treatment at the end of the study), quality of life, withdrawal symptoms, craving, additional drug consumption, driving capacity and adverse events were collected. We identified 13 articles corresponding to nine clinical trials considering the use of SROM for OMT. Among them, only one was a randomized trial and one was a controlled not randomized trial. All other studies were uncontrolled. Retention rates were good (from 80.6 to 95%) with SROM maintenance, but similar retention rates were obtained with methadone. Most of the studies showed that quality of life, withdrawal symptoms, craving and additional drug consumption improved with SROM. However, there was no comparison with other maintenance drugs. As most of the studies assessing SROM efficacy were uncontrolled, there is no definite evidence that SROM is an effective alternative to methadone for OMT.

What is the most appropriate period to define synchronous cancers?

BACKGROUND: Studies about second primary cancers (SPC) incidence exclude a period following the first cancer diagnosis given the high probability of diagnosing another primary cancer during this phase (synchronous cancers). However, definition of synchronicity period varies widely, from one to six months, without clear epidemiological justification. The objective of this study was to determine the most appropriate synchronicity period. METHODS: Data from 13 French population-based cancer registries were used to establish a cohort of all patients diagnosed with a first cancer between 1989 and 2010. The incidence rate of subsequent cancer was computed by day within 1 year of follow-up after the first diagnosis. Incidence was modelized by joinpoint regression models with an initial quadratic trend and a second constant part (plateau). The joinpoint was the point from which the plateau began and defining the synchronicity period. RESULTS: Our cohort included 696,775 patients with a first cancer, of which 12,623 presented a SPC. The median joinpoint for all sites combined was estimated at 120.5 days [112.0-129.0]. Analysis by gender reported a higher difference in 32 days for males (127.8 vs 96.1 days). Noteworthy differences were found depending on patient age and the site of first cancer, with joinpoint ranging from 84.7 (oesophagus cancer) to 250.1 days (bladder cancer). CONCLUSION: Although some heterogeneity was observed based on the characteristic of the patients, the appropriate synchronicity period appears to be 4 months after the diagnosis of first cancer.

Machine learning application for incident prostate adenocarcinomas automatic registration in a French regional cancer registry.

Cancer registries are collections of curated data about malignant tumor diseases. The amount of data processed by cancer registries increases every year, making manual registration more and more tedious. OBJECTIVE: We sought to develop an automatic analysis pipeline that would be able to identify and preprocess registry input for incident prostate adenocarcinomas in a French regional cancer registry. METHODS: Notifications from different sources submitted to the Bas-Rhin cancer registry were used here: pathology data and, ICD 10 diagnosis codes from hospital discharge data and healthcare insurance data. We trained a Support Vector Machine model (machine learning) to predict whether patient's data must be considered or not as a prostate adenocarcinoma incident case that should therefore be registered. The final registration of all identified cases was manually confirmed by a specialized technician. Text mining tools (regular expressions) were used to extract clinical and biological data from non-structured pathology reports. RESULTS: We performed two successive analyses. First, we used 982 cases manually labeled by registrars from the 2014 dataset to predict the registration of 785 cases submitted in 2015. Then, we repeated the procedure using the 2089 cases labeled by registrars from the 2014 and 2015 datasets to predict the registration of 926 cases submitted in the 2016 data. The algorithm identified 663 cases of prostate adenocarcinoma in 2015, and 610 in 2016. From these findings, 663 and 531 cases were respectively added to the registry; and 641 and 512 cases were confirmed by the specialized technician. This registration process has achieved a precision level above 96 %. The algorithm obtained an overall precision of 99 % (99.5 % in 2015 and 98.5 % in 2016) and a recall of 97 % (97.8 % in 2015 and 96.9 % in 2016). When the information was found in pathology report, text mining was more than 90 % accuracy for major indicators: PSA test, Gleason score, and incidence date). For both PSA and tumor side, information was not detected in the majority of cases." CONCLUSION: Machine learning was able to identify new cases of prostate cancer, and text mining was able to prefill the data about incident cases. Machine-learning-based automation of the registration process could reduce delays in data production and allow investigators to devote more time to complex tasks and analysis.

Should we screen patients for carotid artery disease before lung cancer resection?

BACKGROUND: Postoperative stroke is a rare complication after lung cancer surgery but has a high mortality rate. No strategy has been recommended to detect carotid artery disease preoperatively in lung cancer patients. The main objective of this study was to evaluate whether a routine carotid duplex ultrasound (DUS) altered the preoperative management of these patients. METHODS: We performed a single-centre, retrospective study of all patients referred for lung cancer resection over a two-year period and reviewed the available carotid DUS results. We quantified the number of carotid artery disease diagnosis, the severity of the disease according to DUS results, and the number of treatments initiated preoperatively. We examined relationships between cardiovascular history and preoperative carotid artery disease diagnosis. RESULTS: Among the 398 consecutive lung surgery patients, 6% had a preoperative history of stroke or transient ischemic attack, and one developed a postoperative stroke, of cardioembolic origin. Three hundred and seven patients (77%) had preoperative carotid DUS. Carotid DUS results elicited anti-platelet therapy initiation or endarterectomy before lung resection in 7 out of these 307 patients (2.3%). One hundred and seventy-one carotid DUS were retrospectively reviewed by an expert, who diagnosed carotid stenosis >50% and occlusion in 2.3% and 1.2% of patients, respectively. Abnormal carotid DUS was associated with history of lower extremity artery disease (P<0.001), diabetes mellitus (P<0.05) and dyslipidemia (P<0.05). CONCLUSIONS: This retrospective observational study showed that routine preoperative carotid DUS led to few carotid stenosis detection and few perioperative management alterations. Carotid artery disease diagnosis was associated with cardiovascular history and risk factors. Future studies should examine how to select patients who will benefit from a preoperative carotid DUS.

Evolution of patients' complaints in a French university hospital: is there a contribution of a law regarding patients' rights?

BACKGROUND: Legislative measures have been identified as one effective way of changing attitude or behaviour towards health care. The aim of this study was to describe trends in patients' complaints for medical issues; to evaluate the contribution of a law regarding patients' rights, and to identify factors associated to patients' perception of a medical error. METHODS: Patients with a complaint letter for medical issues in a French university hospital were included. Trends in complaint rates were analysed. Comparisons were made between a first (1998-2000) and a second (2001-2004) time period, before and after the diffusion of the law, and according to the perception of a medical error. RESULTS: Complaints for medical issues increased from 1998 to 2004. Of 164 complaints analysed, 66% were motivated by the perception of a medical error (47% during the first time period vs. 73% during the second time period; p = 0.001). Error or delay in diagnosis/treatment and surgical/medical complication were the main reasons for complaints. Surgical departments had the higher number of complaints. Second time period, substandard care, disability, and adverse effect of a health product were independently associated with the perception of a medical error, positively for the formers, and negatively for the latter. CONCLUSION: This study revealed an increase with time in the number of complaints for medical issues in a university hospital, as well as an increase in the perception of a medical error after the passing of a law regarding patients' rights in France.

Constitutive or Induced HIF-2 Addiction is Involved in Resistance to Anti-EGFR Treatment and Radiation Therapy in HNSCC.

BACKGROUND: management of head and neck squamous cell carcinomas (HNSCC) include anti-Epidermal Growth Factor Receptor (EGFR) antibodies and radiotherapy, but resistance emerges in most patients. RAS mutations lead to primary resistance to EGFR blockade in metastatic colorectal cancer but are infrequent in HNSCC, suggesting that other mechanisms are implicated. Since hypoxia and Hypoxia Inducible Factor-1 (HIF-1) have been associated with treatment failure and tumor progression, we hypothesized that EGFR/mammalian Target Of Rapamycin (mTOR)/HIF-1 axis inhibition could radiosensitize HNSCC. METHODS: We treated the radiosensitive Cal27 used as control, and radioresistant SQ20B and UD-SCC1 cells, in vivo and in vitro, with rapamycin and cetuximab before irradiation and evaluated tumor progression and clonogenic survival. RESULTS: Rapamycin and cetuximab inhibited the mTOR/HIF-1α axis, and sensitized the SQ20B cell line to EGFR-inhibition. However, concomitant delivery of radiation to SQ20B xenografts increased tumor relapse frequency, despite effective HIF-1 inhibition. Treatment failure was associated with the induction of HIF-2α expression by cetuximab and radiotherapy. Strikingly, SQ20B and UD-SCC1 cells clonogenic survival dropped <30% after HIF-2α silencing, suggesting a HIF-2-dependent mechanism of oncogenic addiction. CONCLUSIONS: altogether, our data suggest that resistance to EGFR inhibition combined with radiotherapy in HNSCC may depend on tumor HIF-2 expression and underline the urgent need to develop novel HIF-2 targeted treatments.

Biomechanical effects of osteoplasty with or without Kirschner wire augmentation on long bone diaphyses undergoing bending stress: implications for percutaneous imaging-guided consolidation in cancer patients.

BACKGROUND: Osteoplasty has been discouraged in long bones. However, despite a substantial lack of pre-clinical biomechanical tests, multiple clinical studies have implemented a wide range of techniques to optimise long bone osteoplasty. The aim of the present study is to evaluate the biomechanical properties of osteoplasty alone and in combination with Kirschner wires (K-wires) in a cadaveric human diaphyseal model undergoing 3-point bending stress. METHODS: Thirty unpaired human cadaveric hemi-tibia specimens were randomly assigned to receive no consolidation (group 1, n = 10), osteoplasty alone (group 2, n = 10), or K-wires augmented osteoplasty (group 3, n = 10). Specimens were tested on a dedicated servo-hydraulic machine using a 3-point bending test. Fracture load was calculated for each specimen; two-sample Wilcoxon rank-sum tests were used to assess differences between groups. RESULTS: Median volume of polymethyl methacrylate injected was 18 mL for group 2 (25th-50th percentile 15-21 mL) and 19 mL for group 3 (25th-50th percentile 17-21). There were no significant differences in fracture load between groups 1 and 2 (z = - 0.793; p = 0.430), between groups 1 and 3 (z = - 0.944; p = 0.347), and between groups 2 and 3 (z = - 0.454; p = 0.650). Fractures through the cement occurred in 4 of 30 cases (13.3%); there were no K-wires fractures. CONCLUSIONS: Osteoplasty with or without K-wires augmentation does not improve the resistance of diaphyseal bone to bending stresses.

Use of a case-mix approach to study the trends in the incidence of second primary cancers.

PURPOSE: To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution. METHODS: Cases registered by 13 French cancer registries between 1989 and 2010 and followed-up until June 2013 were included. The person-year approach was used to compute standardized incidence ratios (SIRs) of metachronous SPC. Usual SIRs and cancer site-specific weighted SIRs called "case-mix SIRs" (cmSIRs) were estimated by sex and calendar period of first cancer diagnosis. Calendar trends in SIRs and cmSIRs were compared. RESULTS: More than 2.9 million person-years at risk were included. Among males, SIRs dropped from 1.49 to 1.23 between 1989-1994 and 2005-2010, while cmSIRs decreased from 1.40 to 1.27. This difference seems mainly related to a stronger representation of prostate cancers (at lower risk of SPC) and a weaker contribution of bladder and head and neck cancers (at higher risk of SPC) in recent periods of diagnosis. Among females, both SIRs and cmSIRs have remained stable at around 1.22 and 1.21, respectively. CONCLUSIONS: The cmSIR is an indicator that is not influenced by changes in first cancer site distribution. Its use should be encouraged to assess second cancer incidence control.

SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients.

Lymph node metastasis is an important prognosis factor in non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c-MET, and CAIX), and transcription factors (EMT-TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2). Partial EMT was more frequent in N1-2 (N+) vs N0 patients (P < .01). TGFB1 (P = .02) as well as SNAI2 (P < .01) and TWIST1 (P = .04) were the most differentially expressed genes in N+ tumors. In this group, ZEB1 was correlated with all EMT inducers and other EMT-TFs were overexpressed depending on the inducers. CAIX was an independent prognostic factor for overall survival (IC 95% HR: 1.10-5.14, P = .03). Partial EMT is involved in lymph node progression of NSCLC patients and depends on the TGFß pathway. EMT-TFs are differentially expressed depending on EMT inducers. CAIX might be a relevant prognostic marker in early stage NSCLC.

Reporting reactive cellular changes on smears among women who undergo cervical cancer screening: results of a cohort study after seven years of follow-up.

OBJECTIVE: To identify whether women presenting with reactive cellular changes (RCC) on their cervical smear face an increased risk for developing high grade cervical intraepithelial neoplasia (CIN2-3) or cancer as compared with women with an entirely normal smear. STUDY DESIGN: French data from the association in charge of organized cervical cancer screening in Bas-Rhin administrative region were used to establish a cohort of 96,215 women presenting with a smear classified as entirely normal or with RCC during the year 2001. The Kaplan-Meyer method was used to calculate the probabilities of CIN2-3 and cancer at seven years of follow-up. Univariate and multivariate survival analyses were performed using Cox proportional hazard models. RESULTS: Among the 95,559 women included in the final analysis, 32.2% presented a smear with RCC. After seven years of follow-up, 441 women developed a CIN2-3 and 35 a cancer. Probability of CIN2-3 was increased in the RCC group as compared with the group of women with a normal smear (0.7% versus 0.5%, p=0.002). Multivariate analyses showed that, compared with a normal cervical smear, RCC were associated with a significant 37% increased risk of CIN2-3 (HR=1.37 CI95 [1.13-1.66]). However, the risk of cancer was not significantly increased (HR=1.11 CI95 [0.55-2.23]). CONCLUSION: This study showed that, at seven years, women with RCC on their cervical smear face an increased risk of CIN2-3 but no significant increased risk of cancer. The distinction between entirely normal and RCC cervical smears should therefore not lead to specific clinical management.

Methodological issues of assessing the risk of a second cancer occurring in the same site as a first cancer using registry data.

OBJECTIVE: To present methodological issues that can arise with the assessment of the risk of a second primary cancer (SPC) occurring in the same site as a first cancer using registry data. MATERIAL AND METHODS: Data from ten French cancer registries were used, including data for patients with a first prostate cancer (in males), breast cancer (in females), and colon, lung and kidney cancer (in both sexes) diagnosed between 1989 and 2004. Standardized incidence ratios (SIRs) of SPC were computed by excluding, or not, the risk of an SPC at the same site. RESULTS: For prostate cancer, the SIR dropped from 1.11 to 0.72 when the risk of SPC of the prostate was included. SIRs increased from 1.36 to 1.45, from 1.14 to 1.21, from 1.57 to 2.01, and from 1.37 to 1.51 for breast, colon, lung, and kidney respectively. CONCLUSION: The inclusion, or not, of an SPC at the same site can impact on SPC risk estimates.

Development of a model to predict the 10-year cumulative risk of second primary cancer among cancer survivors.

BACKGROUND: To develop a prediction model to quantify the cumulative risk of Second Primary Cancer (SPC) among cancer patients given that they survive their disease. METHODS: A cohort of 293,435 patients based on data from twelve French cancer registries was analyzed. For five first cancer sites, SPC incidence rates were estimated using Poisson regression models. The cumulative risks of SPC were computed for different follow-up times. For comparison purpose, the same method was used to estimate the probability of cancer in the general population. RESULTS: In this population-based cohort, 27,320 patients presented with a SPC. The cumulative risk of SPC varied depending on first cancer site, with a 10-year cumulative probability of SPC ranging from 6.2% for women with breast cancer to 44.0% for men with head and neck cancer. Compared with the general population, the 10-year cumulative risk of SPC was dramatically elevated for tobacco-related first cancers, with an increase of +7.3% for men aged 55 to 64 with a first lung cancer and +35.6% for men aged 45 to 54 with a first head and neck cancer. Lower differences were observed among patients diagnosed with a first prostate cancer (+5.5% among men aged 55 to 64), colorectal (+4.1% for women aged 55 to 64 and +6.3% for men aged 55 to 64), and breast (+2.0% among females aged 75 and older) cancers. CONCLUSION: This study provides physicians with a practical estimate to assess the risk of SPC of their patients more accurately.