Trends in lung cancer survival in the Nordic countries 1990-2016: The NORDCAN survival studies.

OBJECTIVES: The aim of this study was to evaluate if the previously reported improvements in lung cancer survival were consistent across age at diagnosis and by lung cancer subtypes. MATERIALS AND METHODS: Data on lung cancers diagnosed between 1990 and 2016 in Denmark, Finland, Iceland, Norway and Sweden were obtained from the NORDCAN database. Flexible parametric models were used to estimate age-standardized and age-specific relative survival by sex, as well as reference-adjusted crude probabilities of death and life-years lost. Age-standardised survival was also estimated by the three major subtypes; adenocarcincoma, squamous cell and small-cell carcinoma. RESULTS: Both 1- and 5-year relative survival improved continuously in all countries. The pattern of improvement was similar across age groups and by subtype. The largest improvements in survival were seen in Denmark, while improvements were comparatively smaller in Finland. In the most recent period, age-standardised estimates of 5-year relative survival ranged from 13% to 26% and the 5-year crude probability of death due to lung cancer ranged from 73% to 85%. Across all Nordic countries, survival decreased with age, and was lower in men and for small-cell carcinoma. CONCLUSION: Lung cancer survival has improved substantially since 1990, in both women and men and across age. The improvements were seen in all major subtypes. However, lung cancer survival remains poor, with three out of four patients dying from their lung cancer within five years of diagnosis.

TNM stage in the Nordic Cancer Registries 2004-2016: Registration and availability.

BACKGROUND AND PURPOSE: Stage at cancer diagnosis is an important predictor of cancer survival. TNM stage is constructed for anatomic solid cancer diagnoses from tumor size (T), nodal spread (N) and distant metastasis (M) and categorized in groups 0-I, II, II and IV. TNM stage is imperative in cancer diagnosis, management and control, and of high value in cancer surveillance, for example, monitoring of stage distributions. This study yields an overview of TNM availability and trends in stage distribution in the Nordic countries for future use in monitoring and epidemiologic studies. MATERIAL AND METHODS: TNM information was acquired from the cancer registries in Denmark, Norway, Sweden, and Iceland during 2004-2016 for 26 cancer sites in the three former countries and four in Iceland. We studied availability, comparability, and distribution of TNM stage in three periods: 2004-2008, 2009-2013, and 2014-2016, applying a previously validated algorithm of 'N0M0 for NXMX'. For cancers of colon, rectum, lung, breast, and kidney, we examined TNM stage-specific 1-year relative survival to evaluate the quality in registration of TNM between countries. RESULTS: Denmark, Sweden, and Iceland exhibited available TNM stage proportions of 75-95% while proportions were lower in Norway. Proportions increased in Sweden over time but decreased in Denmark. One-year relative survival differed substantially more between TNM stages than between countries emphasizing that TNM stage is an important predictor for survival and that stage recording is performed similarly in the Nordic countries. INTERPRETATION: Assessment and registration of TNM stage is an imperative tool in evaluations of trends in cancer survival between the Nordic countries.

The impact of cancer patient pathway on timing of radiotherapy and survival: a cohort study in glioblastoma patients.

PURPOSE: Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival. METHODS: This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006-2014, and the post CPP implementation group constituted patients diagnosed 2016-2019. We evaluated timing of RT and survival in relation to CPP implementation. RESULTS: A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4-6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001). CONCLUSION: CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.

Pretreatment Patient-reported Overall Health: A Prognostic Factor for Early Overall Mortality After Primary Curative Treatment of Prostate Cancer.

Background and objective: Registry-based studies for prostate cancer (PCa) document higher overall mortality (OM) after high-dose radiotherapy (RT) than after radical prostatectomy (RP). Our aim was to explore the association between pretreatment patient-reported health ("OverallHealth": OH) and curative treatment type, and the impact on early OM. Methods: New PCa patients registered between 2017 and 2019 in the Cancer Registry of Norway (n = 1949) completed the European Organisation for Research and Treatment of Cancer Quality-of-Life Core 30 (QLQ-C30) questionnaire before RP (n = 592) or RT (n = 610) or after allocation to active surveillance (AS; n = 747). We dichotomised the QLQ-C30 summary score to classify patients with un-impaired versus impaired OH. Standard univariable and multivariable analyses with treatment type or OM as the outcome were conducted. The mean observation time was 4.7 years (standard deviation 1.0). Statistical significance was set at p < 0.05. Key findings and limitations: Impaired OH was more frequent in the RT group (38%) than in the RP (25%) or AS (28%) group (p < 0.001). Higher age, higher risk group, and impaired OH increased the probability of undergoinRT rather than RP (p < 0.001). Impaired OH was associated with a twofold higher early OM rate in the RT group (16% vs 8%; p = 0.009) and fourfold higher OM rate in the AS group (13% vs 3%; p < 0.001). These findings remained significant in Cox regression analyses controlled for age and risk group. After RP, only locally advanced high-risk tumours were significantly associated with OM. Unknown psychometrics for the OH variable is the main study limitation. Conclusions and clinical implications: Pretreatment patient-reported impaired OH, measured as the QLQ-C30 summary score, was positively associated with allocation to RT or AS and is a prognostic factor for early OM. Before allocation to RT or AS, elderly patients with PCa should be screened and treated for health problems that can be remedied. Future studies should determine the psychometrics of the QLQ-C30 summary score in comparison to established frailty screening instruments. Patient summary: Patient-reported scores reflecting their overall health can help in choosing curative treatment for prostate cancer and are associated with survival during the first 5 years after treatment.

Stable glioma incidence and increased patient survival over the past two decades in Norway: a nationwide registry-based cohort study.

BACKGROUND: Surveillance of incidence and survival of central nervous system tumors is essential to monitor disease burden and epidemiological changes, and to allocate health care resources. Here, we describe glioma incidence and survival trends by histopathology group, age, and sex in the Norwegian population. MATERIAL AND METHODS: We included patients with a histologically verified glioma reported to the Cancer Registry of Norway from 2002 to 2021 (N = 7,048). Population size and expected mortality were obtained from Statistics Norway. Cases were followed from diagnosis until death, emigration, or 31 December 2022, whichever came first. We calculated age-standardized incidence rates (ASIR) per 100,000 person-years and age-standardized relative survival (RS).  Results: The ASIR for histologically verified gliomas was 7.4 (95% CI: 7.3-7.6) and was higher for males (8.8; 95% CI: 8.5-9.1) than females (6.1; 95% CI: 5.9-6.4). Overall incidence was stable over time. Glioblastoma was the most frequent tumor entity (ASIR = 4.2; 95% CI: 4.1-4.4). Overall, glioma patients had a 1-year RS of 63.6% (95% CI: 62.5-64.8%), and a 5-year RS of 32.8% (95% CI: 31.6-33.9%). Females had slightly better survival than males. For most entities, 1- and 5-year RS improved over time (5-year RS for all gliomas 29.0% (2006) and 33.1% (2021), p < 0.001). Across all tumor types, the RS declined with increasing age at diagnosis. INTERPRETATION: The incidence of gliomas has been stable while patient survival has increased over the past 20 years in Norway. As gliomas represent a heterogeneous group of primary CNS tumors, regular reporting from cancer registries at the histopathology group level is important to monitor disease burden and allocate health care resources in a population.

Survival trends for patients diagnosed with cutaneous malignant melanoma in the Nordic countries 1990-2016: The NORDCAN survival studies.

BACKGROUND: The survival in patients diagnosed with cutaneous malignant melanoma (CMM) has improved in the Nordic countries in the last decades. It is of interest to know if these improvements are observed in all ages and for both women and men. METHODS: Patients diagnosed with CMM in the Nordic countries in 1990-2016 were identified in the NORDCAN database. Flexible parametric relative survival models were fitted, except for Iceland where a non-parametric Pohar-Perme approach was used. A range of survival metrics were estimated by sex, both age-standardised and age-specific. RESULTS: The 5-year relative survival improved in all countries, in both women and men and across age. While the improvement was more pronounced in men, women still had a higher survival at the end of the study period. The survival was generally high, with age-standardised estimates of 5-year relative survival towards the end of the study period ranging from 85% in Icelandic men to 95% in Danish women. The age-standardised and reference-adjusted 5-year crude probability of death due to CMM ranged from 5% in Danish and Swedish women to 13% in Icelandic men. CONCLUSION: Although survival following CMM was relatively high in the Nordic countries in 1990, continued improvements in survival were observed throughout the study period in both women and men and across age.

Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study.

Background: Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed the incidence, management, and prognostic impact of PsP and analyzed factors associated with PsP in a GBM patient cohort. Methods: Consecutive GBM patients diagnosed in the South-Eastern Norway Health Region from 2015 to 2018 who had received RT and follow-up MRI were included. Tumor, patient, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at 3 and 6 months post-radiation using Response Assessment in Neuro-Oncology criteria. Results: A total of 284 patients were included in the study. PsP incidence 3 and 6 months post-radiation was 19.4% and 7.0%, respectively. In adjusted analyses, methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter and the absence of neurological deterioration were associated with PsP at both 3 (p < .001 and p = .029, respectively) and 6 months (p = .045 and p = .034, respectively) post-radiation. For patients retrospectively assessed as PD 3 months post-radiation, there was no survival benefit of treatment change (p = .838). Conclusions: PsP incidence was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that absence of neurological deterioration significantly correlated with PsP. Continuation of temozolomide courses did not seem to compromise survival for patients with PD at 3 months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings.

Prediction of clinically significant recurrence after partial nephrectomy. Data from the Cancer Registry of Norway with more than five years of follow-up.

OBJECTIVE: To determine recurrence incidence after partial nephrectomy (PN) for renal cell carcinoma and identify predictors for local recurrence (LR) and metastasis. MATERIAL AND METHODS: We retrospectively evaluated a cohort of 524 patients from the Cancer Registry of Norway, who underwent PN between January 2014 and December 2015 and were followed-up for >6 years. Patient demographics and pathological characteristics were correlated with recurrence and progression-free survival using Kaplan-Meier and Cox regression analyses. RESULTS: Median patient age was 64 years, and the median tumour size was 2.6 cm. A positive surgical margin (PSM) was observed in 11% of the cases, while the LR and metastasis rates were 3.4% and 3.2%, respectively. PSM (hazard ratio [HR], 55.4; 95% confidence interval [CI], 12.55-244.6), tumour number (HR, 45.4; 95% CI, 6.5-316.1) and stage (HR, 33.5; 95% CI, 5.4-205.3) were independent predictors for LR. Undetermined margin status was also a risk factor for LR. Tumour stage (HR, 41.05; 95% CI, 8.52-197.76), tumour necrosis (HR, 1.3; 95% CI, 0.4-4.31) and age (HR, 1.07; 95% CI, 1.01-1.14) were predictors for metastasis. CONCLUSIONS: Both local and distant recurrences after PN were rare, and the pT stage was a common predictor. PSM or indeterminate surgical margin and tumour number were LR predictors, while age at surgery and the presence of tumour necrosis predicted metastasis.

Do all prostate cancer patients want, and experience shared decision making prior to curative treatment?

OBJECTIVE: In comparable men with non-metastatic prostate cancer, radical prostatectomy (RP), radiotherapy (RAD) and active surveillance (AS) are treatment options with similar survival rates, but different side-effects. Healthcare professionals consider pretreatment shared decision making (SDM) to be an essential part of medical care, though the patients' view about SDM is less known. In this article, we explore prostate cancer (PCa) patients' SDM wish (SDMwish), and experiences (SDMexp).  Material and methods: This is a registry-based survey performed by the Cancer Registry of Norway (2017-2019). One year after diagnosis, 5,063 curatively treated PCa patients responded to questions about their pre-treatment wish and experience regarding SDM. Multivariable analyses identified factors associated with SDM. Statistical significance level: p < 0.05.  Results: Overall, 78% of the patients wished to be involved in SDM and 83% of these had experienced SDM. SDMwish and SDMexp was significantly associated with decreasing age, increasing education, and living with a partner. Compared with the RP group, the probability of SDMwish and SDMexp was reduced by about 40% in the RAD and the AS groups.  Conclusion: Three of four curatively treated PCa wanted to participate in SDM, and this wish was met in four of five men. Younger PCa patients with higher education in a relationship, and opting for RP, wanted an active role in SDM, and experienced being involved. Effective SDM requires the responsible physicians' attention to the individual patients' characteristics and needs.

Nordcan.R: a new tool for federated analysis and quality assurance of cancer registry data.

Aim of the article: We present our new GDPR-compliant federated analysis programme (nordcan.R), how it is used to compute statistics for the Nordic cancer statistics web platform NORDCAN, and demonstrate that it works also with non-Nordic data. Materials and methods: We chose R and Stata programming languages for writing nordcan.R. Additionally, the internationally used CRG Tools programme by International Agency for Research on Cancer (IARC/WHO) was employed. A formal assessment of (GDPR-compliant) anonymity of all nordcan.R outputs was performed. In order to demonstrate that nordcan.R also works with non-Nordic data, we used data from the Netherlands Cancer Registry. Results: nordcan.R, publicly available on Github, takes as input cancer and general population data and produces tables of statistics. Each NORDCAN participant runs nordcan.R locally and delivers its results to IARC for publication. According to our anonymity assessment the data can be shared with international organizations, including IARC. nordcan.R incidence results on Norwegian and Dutch data are highly similar to those produced by two other independent methods. Conclusion: nordcan.R produces accurate cancer statistics where all personal and sensitive data are kept within each cancer registry. In the age of strict data protection policies, we have shown that international collaboration in cancer registry research and statistics reporting is achievable with the federated analysis approach. Undertakings similar to NORDCAN should consider using nordcan.R.

Were cancer patients worse off than the general population during the COVID-19 pandemic? A population-based study from Norway, Denmark and Iceland during the pre-vaccination era.

Background: In a population-based setting, we investigated the risks of testing positive for SARS-CoV-2 and developing severe COVID-19 outcomes among cancer patients compared with the general population. Methods: In nationwide cohorts, we identified all individuals in Norway, Denmark and Iceland who tested positive for SARS-CoV-2 or had a severe COVID-19 outcome (hospitalisation, intensive care, and death) from March until December 2020, using data from national health registries. We estimated standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) comparing cancer patients with the general population. Findings: During the first wave of the pandemic, cancer patients in Norway and Denmark had higher risks of testing SARS-CoV-2 positive compared to the general population. Throughout 2020, recently treated cancer patients were more likely to test SARS-CoV-2 positive. In Iceland, cancer patients experienced no increased risk of testing positive. The risk of COVID-19-related hospitalisation was higher among cancer patients diagnosed within one year of hospitalisation (Norway: SIR = 2.43, 95% CI 1.89-3.09; Denmark: 2.23, 1.96-2.54) and within five years (Norway: 1.58, 1.35-1.83; Denmark: 1.54, 1.42-1.66). Risks were higher in recently treated cancer patients and in those diagnosed with haematologic malignancies, colorectal or lung cancer. Risks of COVID-19-related intensive care and death were higher among cancer patients. Interpretation: Cancer patients were at increased risk of testing positive for SARS-CoV-2 during the first pandemic wave when testing availability was limited, while relative risks of severe COVID-19 outcomes remained increased in cancer patients throughout 2020. Recent cancer treatment and haematologic malignancy were the strongest risk factors. Funding: Nordic Cancer Union.

Impact of prebiopsy MRI on prostate cancer staging: Results from the Norwegian Prostate Cancer Registry.

Objectives: The aim of this study is to evaluate the 2015 introduction of prebiopsy magnetic resonance imaging of the prostate (MRI-P) as the standard of care for diagnosing prostate cancer (PCa) by the Norwegian public health care authorities. There were three specific objectives of this study: first, to evaluate the consequences of using different TNM manuals for clinical T-staging (cT-staging) in a national setting; second, to determine if the data reveals that MRI-P based cT-staging is superior to digital rectal examination (DRE)-based cT-staging compared with pathological T-stage (pT-stage) post radical prostatectomy; and third, to assess whether treatment allocations have changed over time. Materials and Methods: All patients registered in the Norwegian Prostate Cancer Registry between 2004 and 2021 were retrieved and 5538 were eligible for inclusion. Concordance between clinical T-stage (cT-stage) and pT-stage was assessed by percentage agreement, Cohen's kappa and Gwet's agreement. Results: MR visualisation of lesions influences reporting of tumour extension beyond DRE findings. Agreement between cT-stage and pT-stage declined from 2004 to 2009, which coincided with an increase in the percentage being pT3. From 2010, agreement increased, which aligned with changes in cT-staging and the introduction of MRI-P. From 2017, regarding the reporting of cT-DRE and cT-Total (overall cT-stage), agreement diminished for cT-DRE but remained relatively stable (>60%) for cT-Total. Regarding treatment allocation, the study suggests that staging with MRI-P has shifted treatment towards radiotherapy in locally advanced high-risk disease. Conclusion: Introduction of MRI-P has affected cT-stage reporting. Agreement between cT-stage and pT-stage appears to have improved. This study suggests that use of MRI-P influences treatment decisions in certain patient subgroups.

Influence of various assumptions for the individual TNM components on the TNM stage using Nordic cancer registry data.

BACKGROUND: The stage at diagnosis is one of the most important predictors for cancer survival. TNM stage is constructed from T (tumor size), N (nodal spread), and M (distant metastasis) components. In many notifications to cancer registries, TNM information is incomplete with unknown N and/or M. We aimed to evaluate the influence of various assumptions for recoding missing N (NX) and M (MX) as N0 and M0 on the proportion with available TNM stage, stage-distribution, and stage-specific relative survival. MATERIAL AND METHODS: We identified 140,201 patients diagnosed with incident cancer of the colon, rectum, lung, breast, or kidney during 2014-2016 in Denmark, Norway, Sweden, or Iceland. Information on TNM were obtained from cancer registry records used for an update of the Nordic cancer statistics database NORDCAN. Patients were followed for death or emigration through 2017. We calculated proportions of available TNM stage, stage distribution, and stage-specific relative survival under different approaches for each cancer site and country. RESULTS: Application of the assumptions yielded higher numbers of cases with available TNM stage for stages 0-I, II, and III. We observed only minor differences in stage-specific one-year relative survival when applying N0M0 for missing N and M, especially for high completeness of TNM registrations, whereas relative survival for remaining cases with missing TNM stage declined substantially. CONCLUSION: We found no major changes in stage-specific one-year relative survival applying N0M0 for NXMX. We conclude that complete TNM information is preferable to making assumptions, but it seems reasonable to consider assuming N0M0 for missing N and M in future studies based on the Nordic cancer registries. An automatic algorithm, though, is not recommended without considering potential area-specific reasons for frequent use of NX and MX. Clinicians should be urged to report complete TNM information to improve surveillance of the TNM stage.

Age-specific survival trends and life-years lost in women with breast cancer 1990-2016: the NORDCAN survival studies.

BACKGROUND: A recent overview of cancer survival trends 1990-2016 in the Nordic countries reported continued improvements in age-standardized breast cancer survival among women. The aim was to estimate age-specific survival trends over calendar time, including life-years lost, to evaluate if improvements have benefited patients across all ages in the Nordic countries. METHODS: Data on breast cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway, and Sweden were obtained from the NORDCAN database. Age-standardized and age-specific relative survival (RS) was estimated using flexible parametric models, as was reference-adjusted crude probabilities of death and life-years lost. RESULTS: Age-standardized period estimates of 5-year RS in women diagnosed with breast cancer ranged from 87% to 90% and 10-year RS from 74% to 85%. Ten-year RS increased with 15-18 percentage points from 1990 to 2016, except in Sweden (+9 percentage points) which had the highest survival in 1990. The largest improvements were observed in Denmark, where a previous survival disadvantage diminished. Most recent 5-year crude probabilities of cancer death ranged from 9% (Finland, Sweden) to 12% (Denmark, Iceland), and life-years lost from 3.3 years (Finland) to 4.6 years (Denmark). Although survival improvements were consistent across different ages, women aged ≥70 years had the lowest RS in all countries. Period estimates of 5-year RS were 94-95% in age 55 years and 84-89% in age 75 years, while 10-year RS were 88-91% in age 55 years and 69-84% in age 75 years. Women aged 40 years lost on average 11.0-13.8 years, while women lost 3.8-6.0 years if aged 55 and 1.9-3.5 years if aged 75 years. CONCLUSIONS: Survival for Nordic women with breast cancer improved from 1990 to 2016 in all age groups, albeit with larger country variation among older women where survival was also lower. Women over 70 years of age have not had the same survival improvement as women of younger age.

EGFR-mutation testing and TKI treatment patterns in locally advanced and metastatic NSCLC in Norway - A nationwide retrospective cohort study.

BACKGROUND: Testing for epidermal growth factor receptor mutation (EGFRm) status is a prerequisite to identify eligible patients for tyrosine kinase inhibitors (TKI) treatment. However, EGFR testing of patients with non-small cell lung cancer (NSCLC) is suboptimal in many parts of the world. The aim of this study was to describe real-world EGFR testing practice, EGFRm prevalence, and subsequent TKI treatment patterns in Norway. PATIENTS AND METHODS: This retrospective, observational, cohort study included all incident locally advanced and metastatic non-squamous NSCLC patients registered in the Norwegian Cancer Registry during 2010-2017. A cohort with follow-up through 2018 was formed with linkage to nationwide registries on comorbidities, prescribed drugs and causes-of-death. RESULTS: A total of 10,717 patients were included, of which 35% (3782) with locally advanced NSCLC and 65% (6935) with metastatic disease. Mean age at diagnosis was 71 years and 47% were female. EGFR testing among patients with metastatic NSCLC increased from 41% to >64% between 2010 and 2017, with a relative stable incidence of EGFRm+ (∼9%). More than 85% of EGFRm+ patients received TKI treatment. Patients with the most dismal prognosis (>80 age, comorbidities) and with diagnosis based on cytology/imaging were less likely to be tested. Differences in testing were observed between regions. CONCLUSION: Despite increased test rates over the study period, in Norway, a significant proportion of patients with non-squamous metastatic NSCLC are still not tested for EGFR. To maximize the identification of eligible patients for targeted therapies, increased testing is recommended, regardless of age, comorbidity rate and place of residence.

Late Adverse Health Outcomes and Quality of Life after curative radiotherapy + long-term ADT in Prostate Cancer Survivors: Comparison with men from the general population.

Background: Few studies have described the impact of urinary, bowel and sexual Adverse Health Outcomes (AHOs) on Quality of Life (QoL) in Prostate Cancer Survivors living for more than 5 years after curative radiotherapy ("long-term PCaSs"), and compared the findings with those in men from general population. Here we assess self-reported AHOs in such PCaSs focusing on the association between problem experience and QoL. The findings are compared to corresponding symptoms in age-similar men from the general population without a PCa diagnosis (Norms). Methods: Nine years (mean) after curative radiotherapy 1231 PCaSs and 3156 Norms completed the EPIC-26 questionnaire and the EORTC QLQ-C30 instrument. Domain Summary Scores (DSSs) for the urinary, bowel and sexual domains, the percentages of moderate/big dysfunctions and the proportions of overall problems were determined. Inter-cohort differences were interpreted based on cut-off values for published Minimal Clinically Important Differences (MCIDs). Multivariable linear regression models analyzed the associations between QoL and domain-related overall problems. Results: Only the inter-cohort differences regarding bowel and sexual DSSs exceeded the respective MCIDs. Among PCaSs 54% had at least one moderate/big problem (Norms: 30%). In PCaSs and Norms, QoL increased with decreasing urinary and bowel problems, For sexuality this association was weaker in Norms and was almost lacking in PCaSs. Multivariable-adjusted QoL was similar in PCaSs and Norms, with general health being the strongest covariate. Conclusions: During follow-up of long-term PCaSs health professionals should be aware of the survivors' persisting moderate/big urinary, bowel or sexual problems associated with reduced QoL. In particular , alleviation of urinary and bowel problems can increase the men's QoL.

Time trends in mobile phone use and glioma incidence among males in the Nordic Countries, 1979-2016.

INTRODUCTION: In the Nordic countries, the use of mobile phones increased sharply in the mid-1990s especially among middle-aged men. We investigated time trends in glioma incidence rates (IR) with the perspective to inform about the plausibility of brain tumour risks from mobile phone use reported in some case-control studies. METHODS: We analysed IR of glioma in Denmark, Finland, Norway, and Sweden among men aged 40-69 years, using data from national cancer registries and population statistics during 1979-2016, using log-linear joinpoint analysis. Information on regular mobile phone use and amount of call-time was obtained from major studies of mobile phones in these countries. We compared annual observed incidence with that expected under various risk scenarios to assess which of the reported effect sizes are compatible with the observed IR. The expected numbers of cases were computed accounting for an impact of other factors besides mobile phone use, such as improved cancer registration. RESULTS: Based on 18,232 glioma cases, IR increased slightly but steadily with a change of 0.1% (95 %CI 0.0%; 0.3%) per year during 1979-2016 among 40-59-year-old men and for ages 60-69, by 0.6 % (95 %CI 0.4; 0.9) annually. The observed IR trends among men aged 40-59 years were incompatible with risk ratios (RR) 1.08 or higher with a 10-year lag, RR ≥ 1.2 with 15-year lag and RR ≥ 1.5 with 20-year lag. For the age group 60-69 years, corresponding effect sizes RR ≥ 1.4, ≥2 and ≥ 2.5 could be rejected for lag times 10, 15 and 20 years. DISCUSSION: This study confirms and reinforces the conclusions that no changes in glioma incidence in the Nordic countries have occurred that are consistent with a substantial risk attributable to mobile phone use. This particularly applies to virtually all reported risk increases reported by previous case-control studies with positive findings.

Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries: the impact of decreasing resection rates.

BACKGROUND: We previously observed decreasing resection rates of non-metastatic gastric adenocarcinoma (GaC) in the US and some European countries. If and to what extent these trends affect the trends in overall survival (OS) of patients with non-metastatic GaC at the population level remain unclear. This large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic GaC. METHODS: Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands, Belgium, Sweden, Norway, and Slovenia, and the US Surveillance, Epidemiology, and End Results database. We analyzed data for each country separately. Associations between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables, with and without including resection and chemotherapy as potential explanatory variables. RESULTS: A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed, with an accumulated follow-up of 172,357 person-years. Without adjustment for resection, OS was improved only slightly in the US [hazard ratio (HR)per year = 0.99; HR≥vs.<2010 = 0.96], and no improvement was observed in the investigated European countries, with OS even worsening in Sweden (HRper year = 1.03; HR≥vs.<2010 = 1.17). After adjusting for resection, the increasing OS trend became stronger in the US (HRper year = 0.98; HR≥vs.<2010 = 0.88), and the temporal trend became insignificant in Sweden. In Slovenia (HRper year = 0.99; HR≥vs.<2010 = 0.92) and Norway (HRper year = 0.97; HR≥vs.<2010 = 0.86), improved OS over time emerged after resection adjustment. Improved OS in patients undergoing resection was observed in the US, the Netherlands, and Norway. Adjustment for chemotherapy did not alter the observed associations. Stratified analyses by tumor location showed mostly similar results with the findings in all patients with non-metastatic GaCs regarding the associations between year of diagnosis and survival. CONCLUSIONS: OS of patients with non-metastatic GaC mostly did not improve in selected European countries and was even worsened in Sweden, while it was slightly increased in the US in the early 21st century. Progress in OS of patients with non-metastatic GaC seems to have been impeded to a large extent by decreasing rates of resection.

Survival trends in patients diagnosed with colon and rectal cancer in the nordic countries 1990-2016: The NORDCAN survival studies.

BACKGROUND: Survival of patients with colon and rectal cancer has improved in all Nordic countries during the past decades. The aim of this study was to further assess survival trends in patients with colon and rectal cancer in the Nordic countries by age at diagnosis and to present additional survival measures. METHODS: Data on colon and rectal cancer cases diagnosed in the Nordic countries between 1990 and 2016 were obtained from the NORDCAN database. Relative survival was estimated using flexible parametric models. Both age-standardized and age-specific measures for women and men were estimated from the models, as well as reference-adjusted crude probabilities of death and life-years lost. RESULTS: The five-year age-standardized relative survival of colon and rectal cancer patients continued to improve for women and men in all Nordic countries, from around 50% in 1990 to about 70% at the end of the study period. In general, survival was similar across age and sex. The largest improvement was seen for Danish men and women with rectal cancer, from 41% to 69% and from 43% to 71%, respectively. The age-standardized and reference-adjusted five-year crude probability of death in colon cancer ranged from 30% to 36% across countries, and for rectal cancer from 20% to 33%. The average number of age-standardized and reference-adjusted life-years lost ranged between six and nine years. CONCLUSION: There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present.

Meiotic drive in chronic lymphocytic leukemia compared with other malignant blood disorders.

The heredity of the malignant blood disorders, leukemias, lymphomas and myeloma, has so far been largely unknown. The present study comprises genealogical investigations of one hundred and twelve Scandinavian families with unrelated parents and two or more cases of malignant blood disease. For comparison, one large family with related family members and three hundred and forty-one cases of malignant blood disease from the Faroese population was included. The inheritance is non-Mendelian, a combination of genomic parental imprinting and feto-maternal microchimerism. There is significantly more segregation in maternal than in paternal lines, predominance of mother-daughter combinations in maternal lines, and father-son combinations in paternal lines. Chronic lymphocytic leukemia is the most frequent diagnosis in the family material, and chronic lymphocytic leukemia has a transgenerational segregation that is unique in that inheritance of susceptibility to chronic lymphocytic leukemia is predominant in males of paternal lines. Male offspring with chronic lymphocytic leukemia in paternal lines have a birth-order effect, which is manifest by the fact that there are significantly more male patients late in the sibling line. In addition, there is contravariation in chronic lymphocytic leukemia, i.e. lower occurrence than expected in relation to other diagnoses, interpreted in such a way that chronic lymphocytic leukemia remains isolated in the pedigree in relation to other diagnoses of malignant blood disease. Another non-Mendelian function appears in the form of anticipation, i.e. increased intensity of malignancy down through the generations and a lower age at onset of disease than otherwise seen in cases from the Cancer Registers, in acute lymphoblastic leukemia, for example. It is discussed that this non-Mendelian segregation seems to spread the susceptibility genes depending on the gender of the parents and not equally to all children in the sibling line, with some remaining unaffected by susceptibility i.e. "healthy and unaffected", due to a birth order effect. In addition, anticipation is regarded as a non-Mendelian mechanism that can amplify, «preserve¼ these vital susceptibility genes in the family. Perhaps this segregation also results in a sorting of the susceptibility, as the percentage of follicular lymphoma and diffuse large B-cell lymphoma is lower in the family material than in an unselected material. Although leukemias, lymphomas and myelomas are potentially fatal diseases, this non-Mendelian distribution and amplification hardly play any quantitative role in the survival of Homo sapiens, because these diseases mostly occur after fertile age.