Cancer-related fatigue among long-term survivors of breast, cervical, and colorectal cancer: a French registry-based controlled study.

BACKGROUND: While several studies have documented fatigue during and after cancer treatment, long-term cancer survivor fatigue is underreported. In this study, we compare fatigue, quality of life (QoL), and anxiety between relapse-free cancer survivors 15 years after diagnosis and healthy controls. METHODS: Cancer survivors (CS) were randomly selected from three large population-based cancer registries (Bas-Rhin, Calvados, and Doubs, France). Cancer-free controls were randomly selected from electoral lists with stratification on age group, residence area, and gender. All participants completed self-reported fatigue (MFI), QoL (EORTC QLQ-C30), and anxiety (STAI) questionnaires. Univariable and multivariable logistic regression were used to study the association between fatigue and cancer status, in three cancer subgroups: breast cancer (BC), cervical cancer (CC), and colorectal cancer (CRC). RESULTS: Two hundred sixty-three CS and 688 controls (125/275, 45/153, 93/260 CS/controls for BC, CC, and CRC respectively) were included. The mean age was 66 years. In multivariable analyses, CS had higher general and mental fatigue than controls p = 0.04 and p = 0.02, respectively. No difference in QoL was observed between CS and controls. CS were more anxious than controls (p < 0.01). Anxiety was associated with general fatigue (p < 0.0001) and mental fatigue (p < 0.0001). CONCLUSION: Fifteen years after diagnosis, cancer survivors reported more general and mental fatigue compared with controls. Our results reinforce guidelines, identifying fatigue as a persistent symptom.

Quality of life in long-term cervical cancer survivors: a population-based study.

OBJECTIVES: To assess long-term quality of life (QOL) in cervical cancer survivors (CCSs), 5, 10, and 15 years after diagnosis. METHODS: In a cross-sectional population-based study, CCSs diagnosed in 1990, 1995, or 2000 were randomly selected from 3 tumor registries in France. Healthy controls were randomly selected from electoral rolls, stratifying on age group and residence area. Five QOL questionnaires (SF-36, EORTC QLQ-C30, the cervical cancer-specific module (EORTC QLQ-CX24), the MFI fatigue questionnaire, the STAI for anxiety) and a life condition questionnaire were used. Analysis of variance was used to compare QOL scores of survivors by period of diagnosis (5, 10, and 15 years) with those of controls and according to treatment modality, adjusted for socio-demographic data. RESULTS: A total of 173 localized CCSs (42% treated with surgery alone and 58% with a combination of treatments) and 594 controls participated in the study. Compared with controls, CCSs expressed globally similar good QOL, except for impaired psychoemotional domains in 15-year survivors (p<0.01). Worsening of some symptoms was observed over time, 15-year survivors in particular reported significantly more lymphedema than 5-year (p=0.0009) and 10-year CCSs (p=0.002). Compared with CCSs treated by surgery alone, QOL of CCSs who received radiotherapy was significantly more affected in terms of cervical cancer specific problems, such as sexual dysfunction (p=0.002), voiding and abdominal symptoms (p=0.01), and lymphedema (p=0.01). CONCLUSIONS: Even after 15 years, QOL of CCSs is impacted in psychological domains, compared with healthy controls. Among CCSs, women treated by adjuvant radiotherapy expressed more physical sequelae.

Refining Incidence and Characteristics of Inflammatory Myopathies: A Quadruple-Source Capture-Recapture Survey Using the 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria.

OBJECTIVE: Inflammatory myopathies (IM), characterized by muscle inflammation and weakness, are rare systemic diseases. Our previous study estimated an IM incidence rate of 7.98 cases per million people per year (95% confidence interval 7.38-8.66) and highlighted important variations that were likely because of methodologic issues rather than true epidemiologic differences. In this study, we aimed to refine the incidence of IM, using the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for IM and a quadruple-source capture-recapture method during a 6-year period in Alsace, France, a region with a population of 2 million having benefits of good access to health care and accredited IM referral centers. METHODS: Clinical data of potential IM patients were obtained from 4 sources (general practitioners and community specialists, public and private hospital records, public and private laboratories, and archives from the pathology department). Patients residing in Alsace and who fulfilled the 2017 EULAR/ACR criteria for IM between January 1, 2006, and January 1, 2013, were included. We corrected potentially incomplete ascertainment of cases with capture-recapture analyses. We studied both spatial and temporal distributions of incidence of IM. We also assessed systemic manifestations of the disease. RESULTS: Our review of 1,742 potential cases identified 106 patients with IM. No spatial or temporal heterogeneity was observed. Use of log-linear models showed an estimated 14.9 additional missed cases. Thus, the incidence rate of IM was 8.22 new cases per million inhabitants per year (95% confidence interval 6.76-9.69). Extramuscular manifestations other than dermatomyositis rash were frequently recorded. CONCLUSION: The stringent methodology used in our study provides an accurate estimation of the incidence of IM. This study also demonstrates, in a population-based cohort, the systemic nature of IM.

Health-related quality of life among long-term survivors of colorectal cancer: a population-based study.

BACKGROUND: The number of long-term colorectal cancer survivors is increasing. Cancer and its treatment can cause physical and psychological complications, but little is known about how it impacts quality of life (QOL) over the long term-5, 10, and 15 years after diagnosis. METHODS: Cancer survivors were randomly selected from three tumor registries in France, diagnosed in 1990 (±1 year), 1995 (±1 year), and 2000 (±1 year). Controls were randomly selected from electoral rolls, stratifying on gender, age group, and residence area. Participants completed two QOL questionnaires, a fatigue questionnaire, an anxiety questionnaire, and a life conditions questionnaire. An analysis of variance was used to compare QOL scores of cancer survivors by period of diagnosis (5, 10, and 15 years) with those of controls, adjusted for sociodemographic data and comorbidities. RESULTS: We included 344 colon cancer and 198 rectal cancer survivors and 1,181 controls. In a global analysis, survivors reported a statistically and clinically significant lower score in social functioning 5 years after diagnosis and higher scores in diarrhea symptoms 5 and 10 years after diagnosis. In subgroup analyses, rectal cancer affected QOL in the physical dimensions at 5 years and in the fatigue dimensions at 5 and 10 years. CONCLUSION: Survivors of colorectal cancer may experience the effects of cancer and its treatment up to 10 years after diagnosis, particularly for rectal cancer. Clinicians, psychologists, and social workers must pay special attention to rectal cancer survivors to improve overall management.

Long-term quality of life after breast cancer: a French registry-based controlled study.

Population-based studies on quality of life (QOL) of long-term breast cancer survivors are quite recent and insufficient attention has been paid to the effect of time since diagnosis. We compared long-term QOL of population-based breast cancer survivors 5, 10, and 15 years after diagnosis with that of healthy controls. Breast cancer survivors were randomly selected from three population-based cancer registries (Bas-Rhin, Calvados and Doubs, France) along with healthy controls, stratified for age and place of residence, randomly selected from electoral rolls. Participants completed five self-administered questionnaires: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Short Form-36 (SF-36), Spielberger State-Trait Anxiety Inventory (STAI), Multidimensional Fatigue Inventory (MFI) and a life conditions questionnaire. An analysis of variance was used to compare QOL scores of breast cancer survivors by period (5, 10, or 15 years) of diagnosis with those of controls, adjusted for sociodemographic data and comorbidities. Six hundred and fifty-two cases and 1,188 controls participated in the study. For many QOL scales, scores were significantly different between cancer survivors and controls. A clinically significant difference was evidenced for the fatigue scales, the SF36 physical functioning, role-physical, and role-emotional scales, with more favorable results for controls. Differences decreased with time and 15-year cancer survivors were generally not different from controls. Scores were particularly influenced by age and mean household income. More efforts should be made, specifically during the first 5 to 10 years after diagnosis, to help women with breast cancer to overcome their impairment in QOL.

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.

[Long-term occupational situation after cancer: A French registry-based study]. / Situation professionnelle à long terme après un cancer : étude réalisée à partir de registres de population.

INTRODUCTION: Few studies have explored the long-term occupational situation after cancer. The aim of our study were to study the employment status among long-term cancer survivors and to compare it to cancer-free controls from the general population at 5, 10 or 15 years after cancer diagnosis. METHODS: From data of a registry-based study, long-term survivors from breast,cervical and colorectal cancer, randomly selected from three tumor registries in France, were compared to cancer-free controls randomly selected from electoral lists. We selected active cancer survivors and cancer-free controls aged less than 60 at the time of the survey. We have studied the employment status of cases vs. controls and the factors associated with employment status. RESULTS: At 5, 10 or 15 years after diagnosis, we did not observe any significant difference in employment status between cases and controls. Among cases, 17% had lost their jobs. Older age, lower incomes, lower education, a short-term employment contract, the presence of co-morbidities, fatigue and a worse quality of life were associated with job loss. DISCUSSION: Although the employment status of the cases was comparable to that of the controls, efforts should be intensified to make it easier for patients diagnosed with cancer to return to work.

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.

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.

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.

Long-Term Follow-Up of Quality of Life following DIEP Flap Breast Reconstruction.

BACKGROUND: Sequelae resulting from breast cancer negatively impact patients' quality of life. Although the deep inferior epigastric perforator (DIEP) flap has become a standard for autologous breast reconstruction, there are limited data regarding long-term quality of life. The authors studied patients' quality of life more than 5 years after DIEP flap breast reconstruction and compare it with two French reference samples. METHODS: A cross-sectional study of quality of life was performed in women who underwent DIEP flap breast reconstruction between 1995 and 2007 using the Medical Outcomes Study 36-Item Health Survey (Short Form-36). The first reference sample included subjects from the French general population (n = 3308), and the second included cancer survivors who underwent mastectomy with (n = 70) or without (n = 135) breast reconstruction. RESULTS: One hundred eleven respondents were analyzed among 186 eligible women. The mean follow-up period after reconstruction was 8.6 years (range, 5 to 15 years). There were no statistically significant differences in the quality of life between women from 45 to 64 years old who underwent DIEP flap breast reconstruction and from the French general population. Five of the eight Short Form-36 dimensions were significantly better in the DIEP flap breast reconstruction group in the 65- to 74-year-old cohort. In addition, quality of life of our study population was significantly higher than that of women who underwent mastectomy with or without any type of breast reconstruction. CONCLUSION: These results indicate that DIEP flap breast reconstruction allows patients with breast cancer to maintain a good postoperative quality of life comparable to that of the general population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Brief Report: Spatial Heterogeneity of Systemic Sclerosis in France: High Prevalence in the Northeast Region.

OBJECTIVE: Alsace is a region in eastern France with a population of ∼2 million. All residents have high access to health care and an accredited referral center for SSc. Seeking care outside of this region is difficult because of the peculiar geography. The aim of this study was to assess the prevalence and spatial variation of systemic sclerosis (SSc) in eastern France. METHODS: Data for SSc patients were obtained from 3 sources (all general practitioners and community specialists, capillaroscopy centers, and all public and private hospital records) and were used to estimate the prevalence of SSc. Surviving patients who resided in Alsace on January 1, 2008 and fulfilled the American College of Rheumatology and/or the LeRoy and Medsger criteria were included in this study. The clinical characteristics of the patients were also assessed. Potentially incomplete case ascertainment was corrected by capture-recapture analyses. Geographic disparities were assessed by spatial cluster analysis and by comparing our results with those for other geographic areas in the world for which data derived using similar methodology were available. RESULTS: The review of 499 potential cases identified a total of 244 SSc patients. A trend toward a west-to-east gradient was observed but did not reach statistical significance. According to log-linear modeling, an estimated 83.87 additional cases were missed. Thus, the SSc prevalence was 228.42 cases per million adult inhabitants of Alsace (95% confidence interval 203.70-253.14); this prevalence was significantly higher than that in 2 other regions of France and comparable with the reported prevalence in Detroit, Michigan. CONCLUSION: The stringent methodology used in the current study is very likely to provide an accurate estimation of the prevalence of SSc. Design similarity with 3 other surveys extends the scope of the results by identifying geographic disparities that were previously indistinguishable due to methodologic differences.

Divergence of host range and biological properties between natural isolate and full-length infectious cDNA clone of the Beet mild yellowing virus 2ITB.

Plant infection by poleroviruses is restricted to phloem tissues, preventing any classical leaf rub inoculation with viral RNA or virions. Efficient virus inoculation to plants is achieved by viruliferous aphids that acquire the virus by feeding on infected plants. The use of promoter-driven infectious cDNA is an alternative means to infect plants and allows reverse genetic studies to be performed. Using Beet mild yellowing virus isolate 2ITB (BMYV-2ITB), we produced a full-length infectious cDNA clone of the virus (named BMYV-EK) placed under the control of the T7 RNA polymerase and the Cauliflower mosaic virus 35S promoters. Infectivity of the engineered BMYV-EK virus was assayed in different plant species and compared with that of the original virus. We showed that in vitro- or in planta-derived transcripts were infectious in protoplasts and in whole plants. Importantly, the natural aphid vector Myzus persicae efficiently transmitted the viral progeny produced in infected plants. By comparing agroinoculation and aphid infection in a host range assay, we showed that the engineered BMYV-EK virus displayed a similar host range to BMYV-2ITB, except for Nicotiana benthamiana, which proved to be resistant to systemic infection with BMYV-EK. Finally, both the BMYV-EK P0 and the full-length clone were able to strongly interfere with post-transcriptional gene silencing.