Diabetes mellitus in long-term survivors with colorectal, breast, or prostate cancer: Prevalence and prognosis. A population-based study.

BACKGROUND: Patients with cancer are at increased risk of diabetes mellitus (DM). Previous studies on the prevalence and prognostic impact of DM in cancer survivors were limited by small sample sizes or short follow-up times. We aimed to compare the patient-reported prevalence of DM in long-term cancer survivors (LTCS), who survived 5 years or more after cancer diagnosis, with that in cancer-free controls, and to estimate the mortality risk among LTCS according to DM status. METHODS: Our population-based cohort comprised 6952 LTCS diagnosed with breast, colorectal, or prostate cancer between 1994 and 2004, recruited in 2008-2011 (baseline), and followed until 2019. A total of 1828 cancer-free individuals served as controls. Multivariable logistic regression was used to compare the prevalence of DM in LTCS and controls, and according to covariates at baseline. Mortality among LTCS according to DM was assessed by Cox proportional hazards regression. RESULTS: A total of 962 (13.8%) LTCS at baseline reported DM. Prevalence of DM in LTCS was not higher than in cancer-free controls, both at baseline (odds ratio, 0.80; 95% CI, 0.66-0.97) and at follow-up (odds ratio, 0.83; 95% CI, 0.67-1.04). Prevalence of DM in LTCS was associated with cancer site, older age, lower education, higher socioeconomic deprivation, higher body mass index, physical inactivity, other comorbidities, and poorer prognosis (adjusted hazard ratio [all-cause mortality] = 1.29; 95% CI, 1.15-1.44). CONCLUSION: DM in LTCS is prevalent, but not higher than in cancer-free population controls. Cancer survivors with concurrent DM are at a potentially higher risk of death. PLAIN LANGUAGE SUMMARY: Cancer and diabetes mellitus (DM) are two serious threats to global health. In our study, prevalence of DM in long-term cancer survivors who survived 5 years or more after cancer diagnosis was not higher than in cancer-free controls. This should not be interpreted as an indication of a lower risk of DM in cancer survivors. Rather, it highlights the potentially poor prognosis in diabetic cancer survivors. Therefore, keeping a continuous satisfactory DM and hyperglycemia management is essential during long-term cancer survivorship.

Trends in cancer incidence by socioeconomic deprivation in Germany in 2007 to 2018: An ecological registry-based study.

Age-standardized cancer incidence has decreased over the last years for many cancer sites in developed countries. Whether these trends led to narrowing or widening socioeconomic inequalities in cancer incidence is unknown. Using cancer registry data covering 48 million inhabitants in Germany, the ecological association between age-standardized total and site specific (colorectal, lung, prostate and breast) cancer incidence in 2007 to 2018 and a deprivation index on district level (aggregated to quintiles) was investigated. Incidence in the most and least deprived districts were compared using Poisson models. Average annual percentage changes (AAPCs) and differences in AAPCs between deprivation quintiles were assessed using Joinpoint regression analyses. Age-standardized incidence decreased strongly between 2007 and 2018 for total cancer and all cancer sites (except female lung cancer), irrespective of the level of deprivation. However, differences in the magnitude of trends across deprivation quintiles resulted in increasing inequalities over time for total cancer, colorectal and lung cancer. For total cancer, the incidence rate ratio between the most and least deprived quintile increased from 1.07 (95% confidence interval: 1.01-1.12) to 1.23 (1.12-1.32) in men and from 1.07 (1.01-1.13) to 1.20 (1.14-1.26) in women. Largest inequalities were observed for lung cancer with 82% (men) and 88% (women) higher incidence in the most vs the least deprived regions in 2018. The observed increase in inequalities in cancer incidence is in alignment with trends in inequalities in risk factor prevalence and partly utilization of screening. Intervention programs targeted at socioeconomically deprived and urban regions are highly needed.

Benefit finding, posttraumatic growth and health-related quality of life in long-term cancer survivors: a prospective population-based study.

BACKGROUND: We explored the relationship between benefit finding (BF)/posttraumatic growth (PTG) at baseline and health-related quality of life (HRQOL) at baseline and follow-up in long-term cancer survivors (LTCS; ≥5-year post-diagnosis). MATERIALS AND METHODS: HRQOL was assessed in LTCS in 2009-2011 (5- to 16-year post-diagnosis, baseline) and re-assessed in 2018/2019 (14- to 24-year post-diagnosis, follow-up). BF and PTG were measured at baseline; mean scores were dichotomized into 'none-to-low' (<3) and 'moderate-to-high' (> =3). Linear regression models and linear mixed regression models were employed to assess the association of BF/PTG with HRQOL. RESULTS: Of the 6057 baseline participants, 4373 were alive in 2019, of whom 2704 completed the follow-up questionnaire. Cross-sectionally, LTCS with none-to-low BF reported better HRQOL at baseline and at follow-up than LTCS with higher BF. Longitudinally, no difference was found between none-to-low and moderate-to-high BF on the HRQOL change from baseline to follow-up. HRQOL differences between the PTG groups were not statistically significant cross-sectionally and longitudinally, except those participants with moderate-to-high PTG reported higher role functioning and global health status/QOL. CONCLUSIONS: Cross-sectionally, BF was significantly negatively related to subscales of HRQOL, while PTG was positively correlated to role functioning and global health status/QOL. The results add further evidence that BF and PTG are two different positive psychological concepts.

Record linkage of claims and cancer registries data-Evaluation of a deterministic linkage approach based on indirect personal identifiers.

PURPOSE: In Germany, record linkage of claims and cancer registry data is cost- and time-consuming, since up until recently no unique personal identifier was available in both data sources. The aim of this study was to evaluate the feasibility and performance of a deterministic linkage procedure based on indirect personal identifiers included in the data sources. METHODS: We identified users of glucose-lowering drugs with residence in four federal states in Northern and Southern Germany (Bavaria, Bremen, Hamburg, Lower Saxony) in the German Pharmacoepidemiological Research Database (GePaRD) and assessed colorectal and thyroid cancer cases. Cancer registries of the federal states selected all colorectal and thyroid cancer cases between 2004 and 2015. A deterministic linkage approach was performed based on indirect personal identifiers such as year of birth, sex, area of residence, type of cancer and an absolute difference between the dates of cancer diagnosis in both data sources of at most 90 days. Results were compared to a probabilistic linkage using "direct" personal identifiers (gold standard). RESULTS: The deterministic linkage procedure yielded a sensitivity of 71.8% for colorectal cancer and 66.6% for thyroid cancer. For thyroid cancer, the sensitivity improved when using only inpatient diagnosis to define cancer in GePaRD (71.4%). Specificity was always above 99%. Using the probabilistic linkage to define cancer cases, the risk for colorectal cancer was estimated 10 percentage points lower than when using the deterministic approach. CONCLUSIONS: Sensitivity of the deterministic linkage approach appears to be too low to be considered as reasonable alternative to the probabilistic linkage procedure.

FUS ALS-causative mutations impair FUS autoregulation and splicing factor networks through intron retention.

Mutations in the RNA-binding protein FUS cause amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease. FUS plays a role in numerous aspects of RNA metabolism, including mRNA splicing. However, the impact of ALS-causative mutations on splicing has not been fully characterized, as most disease models have been based on overexpressing mutant FUS, which will alter RNA processing due to FUS autoregulation. We and others have recently created knockin models that overcome the overexpression problem, and have generated high depth RNA-sequencing on FUS mutants in parallel to FUS knockout, allowing us to compare mutation-induced changes to genuine loss of function. We find that FUS-ALS mutations induce a widespread loss of function on expression and splicing. Specifically, we find that mutant FUS directly alters intron retention levels in RNA-binding proteins. Moreover, we identify an intron retention event in FUS itself that is associated with its autoregulation. Altered FUS levels have been linked to disease, and we show here that this novel autoregulation mechanism is altered by FUS mutations. Crucially, we also observe this phenomenon in other genetic forms of ALS, including those caused by TDP-43, VCP and SOD1 mutations, supporting the concept that multiple ALS genes interact in a regulatory network.

[Linkage of claims data with data from epidemiological cancer registries: possibilities and limitations in the German federal states]. / Verknüpfung von Abrechnungsdaten gesetzlicher Krankenkassen mit Daten epidemiologischer Krebsregister: länderspezifische Möglichkeiten und Limitationen.

BACKGROUND: In recent years, there has been an increasing demand for the reuse of research data in accordance with the so-called FAIR principles. This would allow researchers to conduct projects on a broader data basis and to investigate new research questions by linking different data sources. OBJECTIVES: We explored if nationwide linking of claims data from statutory health insurances (SHI) with data from population-based cancer registries can be used to obtain additional information on cancer that is missing in claims data and to assess the validity of SHI tumour diagnoses. This paper focuses on describing the specific requirements of German federal states for such data linkage. MATERIALS AND METHODS: The Pharmacoepidemiological Research Database GePaRD at the Leibniz Institute for Prevention Research and Epidemiology - BIPS and six cancer registries were used as data sources. The logistically complex direct linkage was compared with a less complex indirect linkage. For this purpose, permission had to be obtained for GePaRD and for each cancer registry from the respective responsible authority. RESULTS: Regarding the linkage of cancer registry data with GePaRD, the cancer registries showed profound differences in the modalities for data provision, ranging from a complete rejection to an uncomplicated implementation of linkage procedures. DISCUSSION: In Germany, a consistent legal framework is needed to adequately enable the reuse and record linkage of personal health data for research purposes according to the FAIR principles. The new law on the consolidation of cancer registry data could provide a remedy regarding the linkage of cancer registry data with other data sources.

Distress mediates the relationship between cognitive appraisal of medical care and benefit finding/posttraumatic growth in long-term cancer survivors.

BACKGROUND: The objective of this study was to ascertain long-term cancer survivors' (LTCS') appraisal of medical care and how these perceptions may influence their health and well-being, including benefit finding (BF) and posttraumatic growth (PTG). METHODS: In total, 6952 LTCS from a multiregional population-based study in Germany completed the Benefit Finding Scale, the Posttraumatic Growth Inventory, the Questionnaire on Stress in Cancer, and self-designed questions on cognitive appraisal of medical care. The authors explored the mediating role of distress between medical care appraisal and BF and PTG and the possible moderation of time since diagnosis in this relationship. RESULTS: LTCS' medical care appraisals ("no unresolved/untreated symptoms," "satisfaction with cancer care," and "satisfaction with care for other diseases") were positively associated with BF. PTG was positively associated with "no unresolved/untreated symptoms" and negatively associated with "satisfaction with care for other diseases." Cancer distress partially mediated the associations between appraisals of medical care and BF, between "no unresolved/untreated symptoms" and PTG and between "satisfaction with care for other diseases" and PTG; whereas it totally mediated the association between "satisfaction with cancer care" and PTG. Time was a significant moderator in the model; the negative indirect effect of cognitive appraisal on BF and PTG through cancer distress weakened with longer time since diagnosis. CONCLUSIONS: Cancer survivors' medical care appraisal is associated with their perceptions of BF and PTG through distress. Therefore, distress screening could be part of the regular workup to identify distressed cancer survivors who are not satisfied with medical care; these survivors may benefit from interventions to reduce distress and increase BF and PTG.

Prevalence of benefit finding and posttraumatic growth in long-term cancer survivors: results from a multi-regional population-based survey in Germany.

BACKGROUND: Cancer studies reported mixed results on benefit finding (BF) and posttraumatic growth (PTG) prevalence and few were focused on long-term survivors. METHODS: BF and PTG were assessed in a multi-regional population-based study in Germany with 6952 breast, colorectal and prostate cancer survivors, using the Benefit Finding Scale and Posttraumatic Growth Inventory. We calculated the age-adjusted prevalence, stratified by demographical and clinical characteristics. RESULTS: Overall, 66.0% of cancer survivors indicated moderate-to-high BF, and 20.5% moderate-to-high PTG. Age-adjusted prevalence of BF and PTG differed according to cancer type (breast > colorectal > prostate) and sex (female > male). BF and PTG prevalence were higher in younger than in older respondents; the age-adjusted prevalence was higher in respondents who survived more years after diagnosis. The strength and direction of associations of age-adjusted prevalence with cancer stage, disease recurrence, and time since diagnosis varied according to cancer type and sex. CONCLUSIONS: A substantial proportion of long-term cancer survivors reported moderate-to-high BF and PTG. However, the prevalence was lower in older and male cancer survivors, and during the earlier years after cancer diagnosis. Further longitudinal studies on PTG and BF in cancer survivors are warranted to address heterogeneity in survivors' experience after cancer diagnosis.

Survival of malignant mesothelioma and other rare thoracic cancers in Germany and the United States: A population-based study.

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000-2014. Patients diagnosed in 1997-2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5-year relative survival (RS). During 2000-2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person-years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5-year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002-2007] vs. 13.0% [2008-2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020-2030 in Western countries.

Age-specific health-related quality of life in disease-free long-term prostate cancer survivors versus male population controls-results from a population-based study.

BACKGROUND: Prostate cancer (PC) and its treatment may affect PC survivors differently with respect to age. However, little is known regarding age-specific health-related quality of life (HRQoL) in PC survivors 5 years or even ≥ 10 years post-diagnosis. METHODS: The sample included 1975 disease-free PC survivors (5-16 years post-diagnosis) and 661 cancer-free population controls, recruited from two German population-based studies (CAESAR+, LinDe). HRQoL in both populations was assessed using the EORTC QLQ-C30 questionnaire. Additionally, PC survivors completed the PC-specific EORTC QLQ-PR25 questionnaire. Differences in HRQoL between survivors and controls, as well as differences according to age and time since diagnosis were analyzed with multiple regression after adjustment for age, education, stage, and time since diagnosis, where appropriate. RESULTS: In general, PC survivors reported HRQoL and symptom-burden levels comparable to the general population, except for significantly poorer social functioning and higher burden for diarrhea and constipation. In age-specific analyses, PC survivors up to 69 years indicated poorer global health and social functioning than population controls. Stratification by time since diagnosis revealed little difference between the subgroups. On PC-specific symptoms, burden was highest for urinary bother and symptoms, and lowest for bowel symptoms. Younger age was associated with less urinary symptoms but higher urinary bother. CONCLUSION: Long-term disease-free PC survivors reported overall good HRQoL, but experienced persistent specific detriments. Our data suggest that these detriments do not improve substantially with increasing time since diagnosis. Targeted interventions are recommended to prevent PC-related and treatment-related symptoms becoming chronic and to enhance social functioning.

Health-related quality of life in long-term disease-free breast cancer survivors versus female population controls in Germany.

PURPOSE: Little is known about breast cancer (BC) survivors' health-related quality of life (HRQoL) > 5 or even > 10 years past diagnosis. It is of interest whether, in the long run, survivors' HRQoL aligns with that of the general population. Study objectives were to (1) compare disease-free BC survivors' HRQoL to that of non-cancer controls, and (2) compare long-term survivors (LTS, 5-9 years post-diagnosis), very long-term survivors (VLTS, ≥ 10 years post-diagnosis), and controls with respect to their HRQoL. METHODS: The samples of 2647 disease-free BC survivors (5-16 years post-diagnosis) and 1005 population controls were recruited in German multi-regional population-based studies. HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Differences in HRQoL were assessed with multiple regression, controlling for age and education. RESULTS: Disease-free BC survivors < 80 years (at survey) reported overall global health status/quality of life comparable to controls, but statistically significant lower physical, role, emotional, social, and cognitive functioning. They also indicated more fatigue, insomnia, dyspnoea, and financial difficulties. However, differences were only of trivial or small clinical relevance. At age 80-89, no differences between BC survivors and controls were observed. Deficits in emotional and cognitive functioning and some symptoms (e.g. insomnia and fatigue) persist, as both LTS and VLTS reported more detriments than controls. CONCLUSIONS: In view of the persistent, small but significant detriments in disease-free BC survivors' cognitive and emotional functioning and higher symptom burden, possibilities to prevent detriments from becoming chronic should be explored.

Age at Diagnosis and Sex Are Associated With Long-term Deficits in Disease-Specific Health-Related Quality of Life of Survivors of Colon and Rectal Cancer: A Population-Based Study.

BACKGROUND: Despite the increasing number of younger individuals diagnosed with colon and rectal cancer, research on the long-term disease-specific health-related quality of life of younger (<50 years) survivors of colon and rectal cancer is scarce. OBJECTIVE: Our study aimed to compare disease-specific functional deficits and symptoms of survivors of colon and rectal cancer 5 to 16 years postdiagnosis, stratified by age at diagnosis and by sex. DESIGN: This is a cross-sectional study. SETTING: We used data from the population-based CAncEr Survivorship-A multi-Regional study in collaboration with 5 population-based German cancer registries. PATIENTS: Survivors of colon and rectal cancer were included in the study. MAIN OUTCOME MEASURES: Respondents completed the disease-specific European Organization for Research and Treatment of Cancer Quality of Life colorectal cancer module. Age at diagnosis categories were <50, 50 to 59, 60 to 69, and ≥70 years. Least square mean health-related quality of life scores, derived from linear regression, were adjusted for sex, education, time since diagnosis, cancer site, cancer stage, and treatment, where appropriate. RESULTS: The sample comprised 697 survivors of colon cancer and 479 survivors of rectal cancer. In general, survivors of colon and rectal cancer diagnosed at <50 years of age reported lower functioning and higher symptom burden in comparison with survivors diagnosed at an older age. When stratified by sex, female survivors of colon cancer tended to report more concerns with hair loss but fewer sexual problems when compared with male survivors of colon cancer of the same age. Female survivors of rectal cancer in all age groups tended to report lower levels of sexual interest than male survivors of rectal cancer of the same age. LIMITATIONS: This was a cross-sectional study with findings that could be biased toward healthier long-term survivors. The generalizability of results is limited to survivors diagnosed before 2005. CONCLUSIONS: Our results suggest that supportive care for survivors of colon and rectal cancer to improve their self-management of symptoms should be adapted according to cancer type, age at diagnosis, and sex. See Video Abstract at http://links.lww.com/DCR/B29. LA EDAD AL DIAGNÓSTICO Y EL GÉNERO ESTÁN ASOCIADOS CON DÉFICITS A LARGO PLAZO EN LA CALIDAD DE VIDA RELACIONADA CON LA SALUD ESPECíFICA DE LA ENFERMEDAD DE LOS SOBREVIVIENTES DE CÁNCER DE COLON Y RECTO: UN ESTUDIO BASADO EN LA POBLACIÓN:: A pesar del creciente número de individuos jóvenes diagnosticados con cáncer de colon y recto, la investigación sobre la calidad de vida relacionada con la salud específica de la enfermedad a largo plazo de los sobrevivientes de cáncer de colon y recto jóvenes (<50 años) es escasa.Nuestro estudio tuvo como objetivo comparar los déficits funcionales específicos de la enfermedad y los síntomas de los sobrevivientes de cáncer de colon y recto 5-16 años después del diagnóstico, estratificados por edad al momento del diagnóstico y por género.Transversal.Utilizamos datos del estudio Supervivencia de CAncEr basada en la población: Un estudio multirregional en colaboración con cinco bases de datos alemanas de cáncer basados en la población.Sobrevivientes de cáncer de colon y recto.Los encuestados respondieron el módulo de calidad de vida específica para la enfermedad en cáncer colorrectal de la Organización Europea para la Investigación y Tratamiento del Cáncer. Las categorías de edad al diagnóstico fueron <50, 50-59, 60-69 y ≥70 años. Los puntajes de CVRS (calidad de vida relacionada a la salud) medios mínimos cuadrados, derivados de la regresión lineal, se ajustaron por género, educación, tiempo desde el diagnóstico, sitio del cáncer, etapa del cáncer y tratamiento, cuando apropiado.La muestra comprendió 697 y 479 sobrevivientes de cáncer de colon y de recto, respectivamente. En general, los sobrevivientes de cáncer de colon y recto diagnosticados con <50 años de edad reportaron una menor funcionalidad y una mayor carga de síntomas en comparación con los sobrevivientes diagnosticados a una edad más avanzada. Cuando se estratificaron por género, las mujeres sobrevivientes de cáncer de colon tendieron a informar más preocupaciones sobre la pérdida de cabello pero menos problemas sexuales en comparación con los hombres sobrevivientes de colon de la misma edad. Las mujeres sobrevivientes de cáncer rectal en todos los grupos de edad tendieron a informar niveles más bajos de interés sexual que los hombres sobrevivientes de cáncer rectal de la misma edad.Estudio transversal con hallazgos que podrían estar sesgados hacia sobrevivientes a largo plazo más saludables. La generalización de los resultados se limitó a los sobrevivientes diagnosticados antes de 2005.Nuestros resultados sugieren que los cuidados de soporte para los sobrevivientes de cáncer de colon y recto para mejorar su automanejo de síntomas deben adaptarse según el tipo de cáncer, la edad en el momento del diagnóstico y el género. Vea el resumen en video en http://links.lww.com/DCR/B29.

Age-specific health-related quality of life in long-term and very long-term colorectal cancer survivors versus population controls - a population-based study.

Background: Previous research suggests an age differential in health-related quality of life (HRQOL) among long-term (5-10 years post-diagnosis, LTS) colorectal cancer (CRC) survivors. Few studies have specifically addressed the association of age differentials with HRQOL for very long-term CRC survivors (>10 years post-diagnosis, VLTS) and non-cancer population controls. We aimed to assess possible deficits in HRQOL of disease-free CRC-LTS and CRC-VLTS in comparison with non-cancer population controls, and whether the observed pattern varies by age and time since diagnosis. Methods: We used data from the CAncEr Survivorship - A multi-Regional (CAESAR+) study in collaboration with five population-based German cancer registries. HRQOL from controls was accessed from the Lebensqualität in DEeutschland (LinDE) study. All respondents completed the European Organization for Research and Treatment of Cancer Quality of Life Core-30 questionnaire. We calculated least square means of HRQOL scores. Analyses were adjusted for age, sex, and education, where appropriate. Results: The sample included 862 CRC-LTS, 400 CRC-VLTS and 1689 controls. CRC survivors reported overall good HRQOL but significantly poorer social functioning and more problems with dyspnea, constipation, diarrhea and finances than controls. When stratified by age, deficits in functioning and global health, and more problems with symptoms and finances were noted mainly among younger CRC survivors. Further stratification by time since diagnosis showed that similar deficits in HRQOL and symptoms were noted mainly among the younger CRC-LTS group when compared with controls. Generally, CRC-VLTS reported comparable HRQOL to controls. An exception was noted for diarrhea, whereby CRC survivors, regardless of age and time since diagnosis, reported significantly more problems with this symptom than controls. Conclusions: In comparison with non-cancer controls, disease-free CRC survivors reported overall good HRQOL but experience persistent specific detriments in HRQOL many years after diagnosis. In age stratified analyses, HRQOL deficits were noted mainly among younger CRC-LTS.

Return to work after cancer. A multi-regional population-based study from Germany.

Background: With improving prognosis, the ability to return to work after cancer has become a realistic goal but only little is known regarding details such as sustainability, financial consequences, and potential determinants of return to work in long-term survivors in Germany. Methods: We studied return to work in a population-based sample of 1558 long-term cancer survivors, diagnosed in 1994-2004 with breast, colorectal or prostate cancer before age 60 (mean 50.1). Information regarding employment status and financial difficulties was obtained via mailed questionnaires from patients who were identified by six population-based cancer registries in Germany. Cumulative incidence of return to work was determined by time-to-event analysis with consideration of competing events. Chi2 tests and multiple logistic regression modeling were employed to identify potential sociodemographic and clinical determinants of return to work. Results: Within a mean period since diagnosis of 8.3 years, 63% of all working-age cancer survivors initially returned to their old job and another 7% took up a new job. Seventeen percent were granted a disability pension, 6% were early retired (not cancer-related), 4% became unemployed, and 1% left the job market for other reasons. Resumption of work occurred within the first 2 years after diagnosis in 90% of all returnees. Cancer-related reduction of working hours was reported by 17% among all returnees and 6% quit their job due to cancer within 5 years past return to work. The probability of return to work was strongly related with age at diagnosis, tumor stage, education, and occupational class but did not differ with respect to the tumor site, gender nor marital status. Conclusions: Most long-term survivors after breast, colorectal, or prostate cancer of working-age are able to return to work. However, financial problems might arise due to a reduction in working hours. An additional provision of targeted interventions for high-risk groups should be discussed.

A population-based registry study on relative survival from melanoma in Germany stratified by tumor thickness for each histologic subtype.

BACKGROUND: Differences in relative survival (RS) of melanoma between histologic subtypes were discussed to be mainly caused by tumor thickness. OBJECTIVE: To investigate RS of melanoma, stratified by tumor thickness for each histologic subtype, and identify survival trends. METHODS: With use of cancer registry data on melanoma cases (International Classification of Diseases, 10th Revision, codes C43.0-C43.9) diagnosed in Germany in 1997-2013, 5- and 10-year age-standardized RS stratified by histologic subtype and stratified or standardized by T stage was estimated by standard and modeled period analyses. We restricted 10-year RS analyses to patients younger than 75 years. RESULTS: We analyzed 82,901 cases. Overall, the 5- and 10-year RS rates were 91.7% and 90.8%, respectively. Prognosis worsened with increasing T stage for all histologic subtypes, but T-stage distribution varied substantially. Survival differences by histologic subtype were strongly alleviated after adjustment for T stage but remained significant. Overall, 5-year RS increased significantly (by 3.8 percentage points) between the periods 2002-2005 and 2010-2013. This increase was no longer seen after adjustment for T stage. LIMITATIONS: Exclusion of cases on account of missing information on T stages, changes in the definition of T stages, and lack of information on screening and treatment limit our analyses. CONCLUSION: Differences in RS between histologic subtypes were strongly mediated by tumor thickness. Over time, RS of melanoma increased as a result of changes in T-stage distribution.

The role of psychosocial resources for long-term breast, colorectal, and prostate cancer survivors: prevalence and associations with health-related quality of life.

PURPOSE: Many long-term cancer survivors still have to adjust to possible adverse consequences of the illness or treatment. Resources can play an important role in this adjustment process, but research on this topic is limited, especially for very long-term survivors. This study explores, which resources are most frequently indicated by different subgroups of cancer survivors, and what role resources play for functioning and health-related quality of life (HRQL) in cancer survivors with and without recurrence. METHODS: The sample of 6030 breast, colorectal, and prostate cancer survivors (5-16 years post-diagnosis) was recruited in a German multi-regional population-based study. Personal resources were assessed by a 27-item checklist; HRQL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). General linear models were used to analyze associations of resources with HRQL. RESULTS: Participants indicated on average 11.4 (SD 5.1) resources as helpful. Family, activities with others, and partnership were indicated most commonly overall, but frequencies varied according to age, sex, and tumor site. Physical activity, health, professional help, calmness, hope, optimism, and hobbies were most important in explaining HRQL variance. Cancer survivors with recurrence and many resources were found to report similar HRQL as survivors without recurrence and only few resources. CONCLUSIONS: The study underlines the importance and situational variability of personal and social resources for cancer survivors' HRQL, even years post-diagnosis. Not only the availability, but also the individual perception and significance of resources should be considered in follow-up cancer care.

Health-related quality of life in long-term survivors with localised prostate cancer by therapy-Results from a population-based study.

OBJECTIVE: Several therapies for localised prostate cancer (PC) are available; all yield similar survival rates. However, each therapy has significant side effects that can influence patients' health-related quality of life (HRQoL) in the long run. METHODS: The study sample included 911 survivors with localised PC, 5-15 years post-diagnosis who were identified from the population-based CAESAR + study in Germany. HRQoL was assessed using the EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. The association between type of therapy and HRQoL was assessed with multivariable linear regression and global F-test adjusting for age, time since diagnosis and comorbidities. RESULTS: Overall, survivors treated with radical prostatectomy (RP) or radiotherapy (RT) alone reported the best HRQoL and the lowest symptom burden. Conversely, survivors treated with androgen deprivation therapy (ADT) (& RP/RT) or RP & RT (in combination) reported the worst HRQoL and the highest symptom burden. Significant differences among treatment groups in HRQoL were found for global health status (p = 0.041), social functioning (p = 0.007), urinary symptoms (p = 0.035), bowel symptoms (p = 0.017) and hormonal treatment-related symptoms (p < 0.001) among other symptoms. CONCLUSIONS: Long-term localised PC survivors formerly treated with a combination of RP and RT or with ADT report poorer HRQoL and more symptoms than patients treated with either RP or RT alone.

[Prospects for a nationwide mortality registry: lessons learned from the Bremen Mortality Index]. / Perspektiven für ein bundesweites Mortalitätsregister: Erfahrungen mit dem Bremer Mortalitätsindex.

The time of death and the diseases leading to death provide important information for health research and disease registries. They facilitate conclusions about the state of health of a population and contribute to the assessment of health promotion measures as well as disease prevention and care. In many countries, these data are provided through mortality registries.In Germany, these data are available on death certificates, which must be filled out by physicians with all information available for each death. However, use of these data for research is very difficult as there is no central registry. Instead, regional health authorities archive the respective death certificates locally. Furthermore, the data provided on death certificates are partly uncoded or only available in paper form. Bremen is the only federal state that has more than 20 years of expertise with a regional mortality registry that demonstrates how health research can benefit from an efficient processing and provision cause of death (CoD) data and how this may also improve the quality of cancer registration.Currently, automatic coding of the CoD by the statistical offices is being implemented on a national level. As a consequence, the free-text information from death certificates will have to be recorded electronically. This requires organizational restructuring that offers a unique opportunity to make all the necessary provisions that are needed for the establishment of mortality registries at the federal state level. This would be an important step towards the establishment of a long overdue national mortality registry - a research data infrastructure guaranteeing international competitiveness.

Strengthening health data on a rare and heterogeneous disease: sarcoma incidence and histological subtypes in Germany.

BACKGROUND: The population-based incidence of sarcoma and its histological subtypes in Germany is unknown. Up-to-date information on a disease with an incidence comparable to other cancer entities is of high public health relevance. The aim of this study was to determine this incidence and to detect significant changes in incidence trends using data from German epidemiological cancer registries. METHODS: Pooled data from the German Centre for Cancer Registry Data with a primary diagnosis occurring in 2013 were used. To date, this is the latest data on cancer incidence available for Germany. All German cancer registries with sufficient completeness were included (10 out of 11), covering a population of 70.0 million people, representing 87% of the German population. All malignant sarcomas according to the RARECARE Project and the WHO classification 2002 were considered for analysis and, above all, gastrointestinal stromal tumours (GIST) of uncertain behaviour. Sensitivity analysis was performed excluding certain histologies. RESULTS: The analysis included 3404 cases in men and 3442 cases in women diagnosed in 2013. The age adjusted sarcoma incidence (European standard) was 7.4 (men) and 6.6 (women) per 100,000 inhabitants. About 70% of sarcomas were soft tissue sarcomas, about 22% GIST, and about 9% bone sarcomas. The most common histological subtypes besides GIST were fibrosarcomas (14%) and liposarcomas (12%) in men and complex mixed and stromal neoplasms (22%), non-uterine leiomysarcomas (10%) and fibrosarcomas (9%) in women. Considering the trend for the years of diagnosis 2004 to 2013, there was a significant increase in incidence for GIST while the incidence of soft tissue sarcomas (only men) as well as of bone sarcoma stayed constant over time. As to soft tissue sarcoma in women, the incidence stayed constant up to the year 2009 and significantly decreased afterwards. CONCLUSION: This study is the first detailed analysis of a German-wide population-based sarcoma incidence showing results comparable to the incidence detected in the RARECARE Project.

An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in Drosophila melanogaster.

RNA surveillance factors are involved in heterochromatin regulation in yeast and plants, but less is known about the possible roles of ribonucleases in the heterochromatin of animal cells. Here we show that RRP6, one of the catalytic subunits of the exosome, is necessary for silencing heterochromatic repeats in the genome of Drosophila melanogaster. We show that a fraction of RRP6 is associated with heterochromatin, and the analysis of the RRP6 interaction network revealed physical links between RRP6 and the heterochromatin factors HP1a, SU(VAR)3-9 and RPD3. Moreover, genome-wide studies of RRP6 occupancy in cells depleted of SU(VAR)3-9 demonstrated that SU(VAR)3-9 contributes to the tethering of RRP6 to a subset of heterochromatic loci. Depletion of the exosome ribonucleases RRP6 and DIS3 stabilizes heterochromatic transcripts derived from transposons and repetitive sequences, and renders the heterochromatin less compact, as shown by micrococcal nuclease and proximity-ligation assays. Such depletion also increases the amount of HP1a bound to heterochromatic transcripts. Taken together, our results suggest that SU(VAR)3-9 targets RRP6 to a subset of heterochromatic loci where RRP6 degrades chromatin-associated non-coding RNAs in a process that is necessary to maintain the packaging of the heterochromatin.