Survival of European adolescents and young adults diagnosed with cancer in 2010-2014.

BACKGROUND: We used the comprehensive definition of AYA (age 15 to 39 years) to update 5-year relative survival (RS) estimates for AYAs in Europe and across countries and to evaluate improvements in survival over time. METHODS: We used data from EUROCARE-6. We analysed 700,000 AYAs with cancer diagnosed in 2000-2013 (follow-up to 2014). We focused the analyses on the 12 most common cancers in AYA. We used period analysis to estimate 5-year RS in Europe and 5-year RS differences in 29 countries (2010-2014 period estimate) and over time (2004-06 vs. 2010-14 period estimates). FINDINGS: 5-year RS for all AYA tumours was 84%, ranging from 70% to 90% for most of the 12 tumours analysed. The exceptions were acute lymphoblastic leukaemia, acute myeloid leukaemia, and central nervous system tumours, presenting survival of 59%, 61%, and 62%, respectively. Differences in survival were observed among European countries for all cancers, except thyroid cancers and ovarian germ-cell tumours. Survival improved over time for most cancers in the 15- to 39-year-old age group, but for fewer cancers in adolescents and 20- to 29-year-olds. INTERPRETATION: This is the most comprehensive study to report the survival of 12 cancers in AYAs in 29 European countries. We showed variability in survival among countries most likely due to differences in stage at diagnosis, access to treatment, and lack of referral to expert centres. Survival has improved especially for haematological cancers. Further efforts are needed to improve survival for other cancers as well, especially in adolescents.

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.

Population-Based Clinical Cancer Registration in Germany.

INTRODUCTION: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years later, the current status of the expanded cancer registration is presented, including current figures on cancer in Germany. METHODS: Reporting of cancer is mandatory for physicians, and about 5 to 10 reports from different healthcare providers are expected for each case. A uniform national dataset of about 130 items is used, and reports are usually sent electronically to the registry. We used the most recent data available from cancer registries up to the year of diagnosis in 2019. We calculated incidence rates and 5-year relative survival (5YRS) for common cancers. Data on clinical outcomes and benchmarking based on quality indicators (QIs) from guidelines were provided by the Cancer Registry Schleswig-Holstein (CR SH). RESULTS: All federal state cancer registries met most of the previously defined national eligibility criteria. Approximately 505,000 cancer cases were registered in 2019, with breast, prostate, colorectal and lung cancer being the most common cancers. The age-standardised cancer incidence has slightly decreased during the last decade. and spatial heterogeneity can be observed within Germany. 5YRS for all cancers was 67% and 63% for women and men, respectively. Therapy data for rectal cancer in 2019-2021 from the CR SH are shown as an example: 69% of the registered patients underwent surgery, mostly with curative intent (84%) and tumour-free resection (91%). Radiotherapy was given to 33% of the patients, and chemotherapy was given to 40%. Three selected QIs showed differences between involved healthcare providers. DISCUSSION: The implementation of population-based clinical cancer registration can be considered a success. Comprehensive recording of diagnosis, treatment and disease progression and the use of registry data for quality assurance, benchmarking and feedback have been implemented.

Persisting Deficits in Health-Related Quality of Life of Colorectal Cancer Survivors 14-24 Years Post-Diagnosis: A Population-Based Study.

(1) Background: The health-related quality of life (HRQOL) of colorectal cancer (CRC) survivors >10 years post-diagnosis is understudied. We aimed to compare the HRQOL of CRC survivors 14-24 years post-diagnosis to that of age- and sex-matched non-cancer controls, stratified by demographic and clinical factors. (2) Methods: We used data from 506 long-term CRC survivors and 1489 controls recruited from German population-based multi-regional studies. HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (EORTC QLQ-C30) questionnaire. We estimated differences in the HRQOL of CRC survivors and controls with multiple regression, adjusted for age at survey, sex, and education, where appropriate. (3) Results: CRC survivors reported poorer social functioning but better health status/QOL than controls. CRC survivors, in general, had higher levels of symptom burden, and in particular diarrhea and constipation, regardless of demographic or clinical factors. In stratified analyses, HRQOL differed by age, sex, cancer type, and having a permanent stoma. (4) Conclusions: Although CRC survivors may have a comparable health status/QOL to controls 14-24 years after diagnosis, they still live with persistent bowel dysfunction that can negatively impact aspects of functioning. Healthcare providers should provide timely and adapted follow-up care to ameliorate potential long-term suffering.

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.

Clinical and sociodemographic determinants of disease-specific health-related quality of life in long-term breast cancer survivors.

PURPOSE: It is important to monitor disease-specific health-related quality of life (HRQoL) in breast cancer (BC) survivors to identify potential unmet supportive care needs. However, previous studies were characterized by small samples of mostly short-term survivors and were limited to certain age ranges, stages and/or treatments. METHODS: We used data from 3045 long-term BC survivors (5-15 years post-diagnosis) recruited in a German multi-regional population-based study. We assessed disease-specific HRQoL with the EORTC QLQ-BR23, scoring from 0 to 100. Differences in functioning and symptoms according to age at survey, self-reported treatments, stage, and disease status (disease-free vs. active disease) were assessed with multiple regression. Active disease was defined as any self-report of recurrence, metastasis or second primary cancer after the index cancer. RESULTS: Older BC survivors reported a higher body image and a better future perspective, but lower sexual functioning. Survivors aged 30-49 years who had breast-conserving therapy or mastectomy with breast reconstruction reported a better body image compared to those who had mastectomy only. We also found differences in symptoms according to treatments in some age groups. Stage at diagnosis was not associated with HRQoL overall and in most age subgroups. Disease-free BC survivors aged 30-79 years reported a better future perspective and less systemic therapy side effects than those with active disease. CONCLUSION: Several treatment-associated symptoms and functioning detriments were found 5-15 years after diagnosis. The results emphasize the need of a comprehensive, individualized survivorship care, recognizing differential needs of long-term BC survivors according to age, treatment modalities, and disease status.

Tethered Function Assays to Elucidate the Role of RNA-Binding Proteins.

The fate of each RNA molecule is strongly determined by RNA-binding proteins (RBPs) which accompany transcripts from its synthesis to its degradation. To elucidate the effect of a specific RBP on bound RNA, it can be artificially recruited to a specific site on a reporter mRNA that can be followed by a variety of methods. In this so-called tethering assay, the protein of interest (POI) is fused to the coat protein of the MS2 bacteriophage and expressed in your favorite cells together with a reporter gene containing MS2 binding sites. The MS2 binding sites are recognized by the MS2 coat protein (MS2CP) with high affinity and specificity and by doing so, the POI is tethered to the reporter RNA. Here, we describe how with the help of this assay the human cytoplasmic poly(A) binding protein is recruited to a mini-µ RNA reporter, thereby influencing the stability of the reporter transcript.

Health and life insurance-related problems in very long-term cancer survivors in Germany: a population-based study.

PURPOSE: Limited research suggests that cancer survivors have problems with insurance. Our study aimed to gain insight into the proportion of very long-term (14-24 years post-diagnosis) survivors of breast, colorectal, and prostate cancers who had problems with health (HI) and life (LI) insurance. METHODS: We used data from CAESAR (CAncEr Survivorship-A multi-Regional population-based study). Participants completed questions on change in insurance providers since cancer diagnosis, problems with requesting (additional) HI or LI, and how potential problems were resolved. We conducted logistic regression to determine factors associated with change in statutory HI. RESULTS: Of the 2714 respondents, 174 (6%) reported having changed HI providers. Most switched between different statutory HI providers (86%), 9% from statutory to private, and 5% from private to statutory. Respondents who changed statutory HI providers were more likely to be prostate cancer survivors (OR 2.79, 95% CI 1.01-7.68) while being ≥ 65 years at time of diagnosis (OR 0.58, 95% CI 0.35-0.96) and having ≥ 2 comorbid conditions (OR 0.61, 95% CI 0.40-0.92) were associated with reduced odds for change. Problems in changing HI were minimal and were resolved with additional contribution. Of the 310 respondents who tried to get LI, 25 respondents reported having difficulties, of whom the majority had their request rejected. CONCLUSION: Most cancer survivors did not change their HI nor tried to buy LI after cancer diagnosis. Problems with changing statutory HI were generally resolved with additional contribution while the main problem encountered when buying LI was rejection of request.

[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.

Health-Related Quality of Life in Very Long-Term Cancer Survivors 14-24 Years Post-Diagnosis Compared to Population Controls: A Population-Based Study.

(1) Background: Little is known about the health-related quality of life (HRQoL) in very long-term cancer survivors (VLTCS) 10 and more years post-diagnosis. The objective was to compare cancer survivors' HRQoL 14-24 years post-diagnosis with that of same-aged non-cancer controls, stratified by age, sex, and disease status (disease-free vs. stage IV, recurrence, metastasis, or second cancer). (2) Methods: We recruited 2704 very long-term survivors of breast, colorectal and prostate cancer, and 1765 controls in German multi-regional population-based studies. The HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Differences in the HRQoL were estimated with multiple regression, controlling for age, sex (where appropriate), and education. (3) Results: The overall global health status/quality of life of VLTCS more than a decade after diagnosis was slightly higher than that of population controls of the same age, but more symptoms and lower functioning were reported. Differences were small but statistically significant. Results differed by age, sex, and disease status. (4) Conclusions: The findings point out the need for a comprehensive survivorship care program in order to monitor and treat potential late and long-term effects after the diagnosis and treatment of cancer. Survivorship care should be risk-adapted to survivors' needs according to sociodemographic and clinical factors.

Age-specific prevalence and determinants of depression in long-term breast cancer survivors compared to female population controls.

BACKGROUND: Depression is more prevalent in breast cancer (BC) survivors than in the general population. However, little is known about depression in long-term survivors. Study objectives were: (1) to compare the age-specific prevalence of depressive symptoms (a) in BC survivors vs female population controls, (b) in disease-free BC survivors vs BC survivors with self-reported recurrence vs controls, and (2) to explore determinants of depression in BC survivors. METHODS: About 3010 BC survivors (stage I-III, 5-16 years post-diagnosis), and 1005 population controls were recruited in German multi-regional population-based studies. Depression was assessed by the Geriatric Depression Scale-15. Prevalence of mild/severe and severe depression only were estimated via logistic regression, controlling for age and education. Multinomial logistic regression was used to explore determinants of mild and severe depression. RESULTS: Compared with population controls, BC survivors were more likely to report mild/severe depression (30.4% vs 23.8%, p = .0003), adjusted for age and education. At all age groups <80 years, prevalence of both mild/severe and severe depression only was significantly higher in BC survivors, while BC survivors ≥80 years reported severe depression less frequently than controls. BC survivors with recurrence reported significantly higher prevalence of mild/severe depression than disease-free survivors and controls, but prevalence in disease-free survivors and controls was comparable. Age, income, living independently, recurrence, and BMI were significant determinants of mild depression in BC survivors. Age, education, employment, income, recurrence, and BMI were significant determinants of severe depression. CONCLUSIONS: Long-term BC survivors <80 years report significantly higher prevalence of depressive symptoms than controls, which might be explained by recurrence and individual factors. The findings suggest that depression in BC survivors is common, and even more after BC recurrence. Clinicians should routinize screening and normalize referral to psychological care.

Divergent Patterns and Trends in Breast Cancer Incidence, Mortality and Survival Among Older Women in Germany and the United States.

BACKGROUND: Breast cancer treatment has changed tremendously over the last decades. In addition, the use of mammography screening for early detection has increased strongly. To evaluate the impact of these developments, long-term trends in incidence, mortality, stage distribution and survival were investigated for Germany and the United States (US). METHODS: Using population-based cancer registry data, long-term incidence and mortality trends (1975-2015), shifts in stage distributions (1998-2015), and trends in five-year relative survival (1979-2015) were estimated. Additionally, trends in five-year relative survival after standardization for stage were explored (2004-2015). RESULTS: Age-standardized breast cancer incidence rates were much higher in the US than in Germany in all periods, whereas age-standardized mortality began to lower in the US from the 1990s on. The largest and increasing differences were observed for patients aged 70+ years with a 19% lower incidence but 45% higher mortality in Germany in 2015. For this age group, large differences in stage distributions were observed, with 29% (Germany) compared to 15% (US) stage III and IV patients. Age-standardized five-year relative survival increased strongly between 1979-1983 and 2013-2015 in Germany (+17% units) and the US (+19% units) but was 9% units lower in German patients aged 70+ years in 2013-2015. This difference was entirely explained by differences in stage distributions. CONCLUSIONS: Overall, our results are in line with a later uptake and less extensive utilization of mammography screening in Germany. Further studies and efforts are highly needed to further explore and overcome the increased breast cancer mortality among elderly women in Germany.

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.

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.

Long-term relative survival from melanoma in Germany 1997-2013.

Up-to-date melanoma relative survival (RS) estimates and trend analysis facilitate close monitoring of melanoma patients' prognosis. This study aimed to provide recent 5-year and 10-year RS from melanoma, stratified by prognostic factors, and identify latest survival trends. Data from 12 German cancer registries were analysed. We included patients with primary cutaneous malignant melanoma (ICD-10: C43.X) diagnosed in 1997-2013 who were at least 15 years old. Five-year and 10-year RS were estimated by period analysis. For 10-year RS analyses, we excluded patients who were 75 years of age or older. Analyses were stratified by sex, age, histology, tumour stage, and body site. We included 82 901 patients, of whom 51% were women. The median age at diagnosis was 62 years. Five-year and 10-year RS in 2007-2013 were 92.4 and 90.8%, respectively. RS was higher in women. The prognosis worsened with older age and higher stage. In superficial spreading melanoma and lentigo maligna melanoma, RS was high; it was lower in nodular, acral lentiginous and 'other' melanoma. RS was the highest for melanoma on the arms; RS for melanoma on unknown or overlapping sites of the skin was the lowest. Five-year and 10-year RS increased significantly from 2005-2007 and 2008-2010 to 2011-2013, by 3.5 and 3.3 percentage points, respectively. For melanoma of 'other' histology, 5-year and 10-year RS increased significantly. Ten-year RS also increased significantly in men with superficial spreading melanoma and T4 melanoma, and in women with T3 melanoma. Melanoma RS improved, especially in certain subgroups. The reasons for improvements need to be investigated further.

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.