Publications by authors named "Klaus Kaae Andersen"

76 Publications

Posterior uveal melanoma incidence and survival by AJCC tumour size in a 70-year nationwide cohort.

Acta Ophthalmol 2021 Mar 18. Epub 2021 Mar 18.

Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Purpose: While early treatment of posterior uveal melanoma can save the eye, the effect of early treatment on survival remains unknown. Therefore, we aimed to determine whether the tumour size at diagnosis has changed over time, and if this has affected survival rates of patients with posterior uveal melanoma in Denmark.

Methods: Nationwide retrospective cohort study linking data from registry-based resources to data from clinical charts and pathology records. Including all Danish patients diagnosed with posterior uveal melanoma from 1943 to 2017. Incidence rates were estimated as annual percentage change (APC) overall and by American Joint Committee on Cancer (AJCC) tumour sizes. The age-period-cohort model was applied to estimate the relative risk of calendar period. The cox proportional hazards model, relative survival Kaplan-Meier curves and cumulative incidence curves were applied to estimate the effect of calendar period on survival.

Results: An overall increase in incidence rate of uveal melanoma was found (APC = 0.25%, 0.08-0.42; 95% CI). This was due to increasing incidence rate of AJCC T1 + T2 tumours (APC = 0.97%, 0.57-1.37; 95% CI), whereas no increase in incidence rates of AJCC T3 + T4 tumours was found (APC = -0.01%, -0.26 to 0.25; 95% CI). The disease-specific survival improved with calendar period for all tumour sizes (HR = 0.988; 0.984-0.993; 95% CI).

Conclusion: Increasing incidence rate and improved survival rate for uveal melanoma was found concordantly with a decrease in tumour size during a 70-year period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14847DOI Listing
March 2021

Adverse health behaviours in long-term testicular cancer survivors: a Danish nationwide study.

Acta Oncol 2021 Mar 1;60(3):361-369. Epub 2020 Dec 1.

Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Treatment for disseminated testicular cancer increases the risk of secondary malignancy and cardiovascular disease. The risk of developing these serious adverse effects may be positively affected by healthy living. The purpose of this study was to identify health behaviours with possible influence on late effects that could be targets for intervention.

Material And Methods: In this cross-sectional study, testicular cancer survivors diagnosed in the period 1984-2007 from the Danish Testicular Cancer database completed a questionnaire on health behaviours (2014-2016). We estimated prevalence of smoking, alcohol consumption, sedentary lifestyle and overweight. Prevalence ratios described with 95% confidence intervals of adverse health behaviours were stratified by treatment modalities and compared to a reference population by means of logistic regression with adjustment for sociodemographic confounders.

Results: In total, 2395 testicular cancer survivors (surveillance, 1175; chemotherapy, 897; radiotherapy, 323), median time since diagnosis 19 years, and 65,289 noncancer males were included, questionnaire response rates were 60% and 54%, respectively. There were more current smokers (prevalence ratio; 1.14, 95% confidence interval (CI): 1.03-1.26) and patients with body mass index above 25 kg/m (prevalence ratio; 1.10, 95% CI: 1.01-1.20) among testicular cancer survivors than in the reference population. Testicular cancer survivors reported less sedentary lifestyle (prevalence ratio; 95% CI: 0.74, 0.64-0.85) and everyday drinkers were fewer (prevalence ratio; 0.79, 95% CI: 0.68-0.92) than in the reference population.

Conclusion: We identified smoking cessation as primary target for intervention studies in testicular cancer survivors. The effect of smoking cessation interventions as part of treatment should be investigated. Whether drug-based intervention is effective in minimising the risk of exposure to conventional risk factors for cardiovascular disease is also of interest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2020.1851765DOI Listing
March 2021

Occult primary brain cancers manifesting in the aftermath of ischaemic and haemorrhagic stroke.

Eur Stroke J 2020 Sep 15;5(3):237-244. Epub 2020 Apr 15.

Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark.

Introduction: Symptoms of occult brain cancer may mimic stroke. Misdiagnosis may lead to improper treatment and delayed diagnosis. We characterised strokes associated with occult primary brain cancer and determined risk that ischaemic and haemorrhagic strokes are associated with occult primary brain cancer.

Patients And Methods: All patients with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n = 85,893) and matched 1:10 on age and sex to the Danish background population without a stroke history (n = 858,740). This cohort was linked to the Danish Cancer Registry and prevalence of occult primary brain cancer defined as the event of previously unknown primary brain cancer during a one-year follow-up was estimated. We used Cox regression models to study risk of occult primary brain cancer in comparison to the background population.

Results: Of 77,484 patients with ischaemic strokes, 39 (1 in 2000) were associated with primary brain cancer; of 8409 with haemorrhagic strokes, it was 126 (1 in 66). In the background cohort, 205 (1 in 4000) had occult primary brain cancer. The multivariate stroke risk factor analysis showed that patients with occult primary brain cancer differed significantly from those without occult primary brain cancer indicating they might have stroke mimics rather than true strokes. Strokes associated with occult primary brain cancer tend to be stroke mimics rather than true strokes. Primary brain cancer is rare in patients with ischaemic stroke (1 in 2000); risk that misdiagnosis results in maltreatment is, therefore, very low. Occult primary brain cancers are mainly found among patients with haemorrhagic stroke; they are not uncommon (1 in 66) and should always be kept in mind.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2396987320920101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538762PMC
September 2020

Risk of Renal Cell Carcinoma Associated with Calcium Channel Blockers: A Nationwide Observational Study Focusing on Confounding by Indication.

Epidemiology 2020 11;31(6):860-871

From the Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Background: We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for RCC.

Methods: Using Danish health registries, we conducted a nested case-control study including 7315 RCC cases during 2000-2015. We matched each case with up to 20 controls on age and sex using risk-set sampling. We estimated odds ratios (ORs) for long-term CCB use associated with RCC using conditional logistic regression. We addressed confounding by indication by (1) adjusting for hypertension severity indicators; (2) evaluating dose-response patterns; (3) examining whether other first-line anti-hypertensives were associated with RCC; and (4) using an active comparator new user design by nesting the study in new users of CCBs or angiotensin-converting enzyme inhibitors (ACEIs).

Results: The adjusted OR for RCC associated with long-term CCB use compared to non-use was 1.76 (1.63-1.90). After we additionally adjusted for hypertension severity indicators, the OR remained elevated (OR 1.37; confidence interval [CI] 1.25, 1.49) with evidence of a dose-response pattern. Other anti-hypertensives were also associated with RCC, for example, ACEIs (OR 1.27; 95% CI = 1.16, 1.39) and thiazides (OR 1.22; 95% CI = 1.12, 1.34). In the active comparator new user design, the OR was 1.21 (95% CI = 0.95, 1.53) for use of CCBs compared with ACEIs.

Conclusions: In this population, confounding by indication appeared to explain at least part of the association between RCC and dihydropyridine CCBs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EDE.0000000000001256DOI Listing
November 2020

Occult lung cancer manifesting within the first year after stroke.

J Stroke Cerebrovasc Dis 2020 Sep 18;29(9):105023. Epub 2020 Jun 18.

Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark. Electronic address:

Background: Lung cancer and stroke share smoking as a major cause of disease. We investigated prevalence and risk of occult lung cancer with manifestation during the first year after stroke.

Methods: All patients >40 years of age with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n=85,893) and matched 1:10 on age and sex to the Danish background population without a history of stroke (n=858,740). Linking data to the Danish Cancer Registry we determined prevalence of occult primary lung cancer defined as the event of previously unknown lung cancer during a one-year follow-up in the stroke and the background population. Cox regression models with adjustments for demographics, co-morbidities and stroke risk factors were used to study risk compared to the background population.

Results: Prevalence (per 1000 person-years) of occult lung cancer in the stroke cohort was 5.3; in the background cohort 2.6. Prevalence separately for current smokers (n=26,055) was 9.6; ex-smokers (n=20,035) 6.5; never-smokers (n=27,268) 1.4. Risk of occult lung cancer (adjusted) was increased HR 1.95 in the stroke population. In the stroke population adjusting for stroke risk factors age (HR 1.24 per 10 years) and smoking (HR 7.1 in current smokers; HR 1.6 in ex-smokers) were the only significant risk factors for occult lung cancer.

Conclusions: Occult lung cancer is rarely found in stroke patients who have never smoked. It is not uncommon in smokers in whom 1% of current smokers had occult lung cancer that became manifest within the first year after stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105023DOI Listing
September 2020

Risk of late health effects after soft-tissue sarcomas in childhood - a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia research programme.

Acta Oncol 2020 Oct 21;59(10):1246-1256. Epub 2020 Jul 21.

Unit of Statistics and Pharmaco-epidemiology, Danish Cancer Society Research Center, Copenhagen, Denmark.

Background: In the 1960s only 1/3 of children with soft-tissue sarcomas survived, however with improved treatments survival today has reached 70%. Given the previous poor survival and the rarity of soft-tissue sarcomas, the risk of somatic late effects in a large cohort of Nordic soft-tissue sarcoma survivors has not yet been assessed.

Methods: In this population-based cohort study we identified 985 five-year soft-tissue sarcoma survivors in Nordic nationwide cancer registries and late effects in national hospital registries covering the period 1964-2012. Information on tumour site and radiotherapy was available for Danish and Finnish survivors ( = 531). Using disease-specific rates of first-time hospital contacts for somatic diseases in survivors and in 4,830 matched comparisons we calculated relative rates (RR) and rate differences (RD).

Results: Survivors had a RR of 1.5 (95% CI 1.4-1.7) and an absolute RD of 23.5 (17.7-29.2) for a first hospital contact per 1,000 person-years. The highest risks in both relative and absolute terms were of endocrine disorders (RR = 2.5; RD = 7.6), and diseases of the nervous system (RR = 1.9; RD = 6.6), digestive organs (RR = 1.7; RD = 5.4) and urinary system (RR = 1.7; RD = 5.6). By tumour site, excess risk was lower after extremity tumours. Irradiated survivors had a 2.6 (1.2-5.9) times higher risk than non-irradiated.

Conclusions: Soft-tissue sarcoma survivors have an increased risk of somatic late effects in 5 out of 10 main diagnostic groups of diseases, and the risk remains increased up to 40 years after cancer diagnosis. Risks were slightly lower for those treated for tumours in the extremities, and radiotherapy increased the risk by more than two-fold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2020.1794031DOI Listing
October 2020

Do repeated transurethral procedures under general anesthesia influence mortality in patients with non-invasive urothelial bladder cancer? A Danish national cohort study.

Scand J Urol 2020 Aug 25;54(4):281-289. Epub 2020 Jun 25.

Department of Urology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

To investigate the effect of repeated transurethral procedures under general anesthesia on overall mortality in patients with non-invasive bladder cancer. All Danish residents with non-invasive papillary urothelial carcinoma or primary urothelial carcinoma diagnosed between 1 January 2000 and 1 January 2011 were included and followed until death or 31 March 2017. All transurethral procedures under general anesthesia, intravesical instillation therapy, recurrences and progression to invasive disease or cystectomy were recorded during follow-up. Associations between treatments and overall mortality were evaluated using multivariable regression analysis adjusted for age, gender, comorbidities and socioeconomic status. The effect of disease progression on mortality was removed by censoring patients at the time of progression or cystectomy. Risk of death increased with the number of transurethral procedures under general anesthesia for Ta low- and high-grade tumors compared to patients who had only one procedure; after eight or more procedures the risk of death increased by 28% and 83%, respectively. There was no similar relationship for carcinomas . In total, 36-52% of procedures under general anesthesia did not identify urothelial neoplasia. Repeated transurethral procedures under general anesthesia appear to be associated with increased risk of death in patients with primary non-invasive papillary urothelial carcinoma. Furthermore, a substantial number of procedures were without findings of neoplasia, indicating that too many patients are admitted for transurethral procedures under GA. Attempts should be taken to reduce unnecessary transurethral procedures under GA, e.g. by improved outpatient diagnosis of urothelial neoplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2020.1782978DOI Listing
August 2020

Types of occult cancer in stroke and the relation to smoking.

Acta Neurol Scand 2020 Nov 13;142(5):486-492. Epub 2020 Jul 13.

Danish Cancer Society Research Center, Copenhagen, Denmark.

Objectives: Stroke is associated with a higher risk of occult cancer. We studied the types of occult cancer most often associated with stroke.

Materials And Methods: All patients with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n = 85 893) and matched 1:10 on age and sex to the Danish background population without history of stroke (n = 858 740). Linking data to the Danish Cancer Registry, we determined the prevalence of occult cancer in stroke defined as the event of previously unknown cancer during a one-year follow-up in the stroke and the background population. We stratified cancers into the 15 most common cancers and into cancers related to and not related to smoking.

Results: Prevalence (per 1000 person-years; stroke/background population) of smoking-related occult cancers (lung, colon, bladder rectum, pancreas, kidney, stomach, and head and neck) was 13.3/8.1 (P < .01) and of cancers not related to smoking (prostate, breast, melanoma, non-Hodgkin lymphoma, ovary, endometrial) it was 6.6/6.2 (P > .05). Among men with stroke prostate (5.8), lung (5.7), and colon cancers (2.9) were most frequent; among women, it was lung (4.7), breast(3.5), and colon cancer(2.8). Among men in the background population, prostate(5.4), lung (3.0), and colon cancers (2.1) were most frequent. Among women, it was breast (3.7), lung(2.1), and colon cancers (1.9).

Conclusion: Stroke patients' increased risk of occult cancer was predominantly for smoking-related cancers while there was no higher risk for the most frequent cancers unrelated to smoking, that is, prostate and breast cancers. Lung cancer is the dominant type of occult cancer in stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13299DOI Listing
November 2020

Comprehensive Evaluation of a Quantitative Shotgun Lipidomics Platform for Mammalian Sample Analysis on a High-Resolution Mass Spectrometer.

J Am Soc Mass Spectrom 2020 Apr 4;31(4):894-907. Epub 2020 Mar 4.

Unit for Cell Death and Metabolism, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Copenhagen DK-2100, Denmark.

Shotgun lipidomics is a powerful tool that enables simultaneous and fast quantification of diverse lipid classes through mass spectrometry based analyses of directly infused crude lipid extracts. We present here a shotgun lipidomics platform established to quantify 38 lipid classes belonging to four lipid categories present in mammalian samples and show the fine-tuning and comprehensive evaluation of its experimental parameters and performance. We first determined for all the targeted lipid classes the collision energy levels optimal for the recording of their lipid class- and species-specific fragment ions and fine-tuned the energy levels applied in the platform. We then performed a series of titrations to define the boundaries of linear signal response for the targeted lipid classes, and demonstrated that the dynamic quantification range spanned more than 3 orders of magnitude and reached sub picomole levels for 35 lipid classes. The platform identified 273, 261, and 287 lipid species in brain, plasma, and cultured fibroblast samples, respectively, at the respective optimal working sample amounts. The platform properly quantified the majority of these identified lipid species, while lipid species measured to be below the limit of quantification were efficiently removed from the data sets by the use of statistical analyses of data reproducibility or a cutoff threshold. Finally, we demonstrated that a series of parameters of cell culture conditions influence lipidomics outcomes, including confluency, medium supplements, and use of transfection reagents. The present study provides a guideline for setting up and using a simple and efficient platform for quantitatively exploring the mammalian lipidome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jasms.9b00136DOI Listing
April 2020

Multisystem burden of neurofibromatosis 1 in Denmark: registry- and population-based rates of hospitalizations over the life span.

Genet Med 2020 06 28;22(6):1069-1078. Epub 2020 Feb 28.

Childhood Cancer Research Group, Danish Cancer Society Research Center, Copenhagen, Denmark.

Purpose: The aim was to assess lifetime risk for hospitalization in individuals with neurofibromatosis 1 (NF1).

Methods: The 2467 individuals discharged with a diagnosis indicating NF1 or followed in a clinical center for NF1 were matched to 20,132 general population comparisons. Based on diagnoses in 12 main diagnostic groups and 146 subcategories, we calculated rate ratios (RRs), absolute excess risks (AERs), and hazard ratios for hospitalizations.

Results: The RR for any first hospitalization among individuals with NF1 was 2.3 (95% confidence interval 2.2-2.5). A high AER was seen for all 12 main diagnostic groups, dominated by disorders of the nervous system (14.5% of all AERs), benign (13.6%) and malignant neoplasms (13.4%), and disorders of the digestive (10.5%) and respiratory systems (10.3%). Neoplasms, nerve and peripheral ganglia disease, pneumonia, epilepsy, bone and joint disorders, and intestinal infections were major contributors to the excess disease burden caused by NF1. Individuals with NF1 had more hospitalizations and spent more days in hospital than the comparisons. The increased risk for any hospitalization was observed for both children and adults, with or without an associated cancer.

Conclusion: NF1 causes an overall greater likelihood of hospitalization, with frequent and longer hospitalizations involving all organ systems throughout life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-020-0769-6DOI Listing
June 2020

DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy.

Autophagy 2020 10 26;16(10):1871-1888. Epub 2020 Jan 26.

Cell Death and Metabolism Unit, Centre for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center (DCRC) , Copenhagen, Denmark.

Macroautophagy/autophagy is a central component of the cytoprotective cellular stress response. To enlighten stress-induced autophagy signaling, we screened a human kinome siRNA library for regulators of autophagic flux in MCF7 human breast carcinoma cells and identified the catalytic subunit of DNA-dependent protein kinase PRKDC/DNA-PKcs as a positive regulator of basal and DNA damage-induced autophagy. Analysis of autophagy-regulating signaling cascades placed PRKDC upstream of the AMP-dependent protein kinase (AMPK) complex and ULK1 kinase. In normal culture conditions, PRKDC interacted with the AMPK complex and phosphorylated its nucleotide-sensing γ1 subunit PRKAG1/AMPKγ1 at Ser192 and Thr284, both events being significantly reduced upon the activation of the AMPK complex. Alanine substitutions of PRKDC phosphorylation sites in PRKAG1 reduced AMPK complex activation without affecting its nucleotide sensing capacity. Instead, the disturbance of PRKDC-mediated phosphorylation of PRKAG1 inhibited the lysosomal localization of the AMPK complex and its starvation-induced association with STK11 (serine/threonine kinase 11). Taken together, our data suggest that PRKDC-mediated phosphorylation of PRKAG1 primes AMPK complex to the lysosomal activation by STK11 in cancer cells thereby linking DNA damage response to autophagy and cellular metabolism. AXIN1: axin 1; 3-MA: 3-methyladenine; 5-FU: 5-fluorouracil; AA mutant: double alanine mutant (S192A, T284A) of PRKAG1; ACACA: acetyl-CoA carboxylase alpha; AICAR: 5-Aminoimidazole-4-carboxamide ribonucleotide; AMPK: AMP-activated protein kinase; ATG: autophagy-related; ATM: ataxia telangiectasia mutated; ATR: ATM serine/threonine kinase; AV: autophagic vacuole; AVd: degradative autophagic vacuole; AVi: initial autophagic vacuole; BECN1: beclin 1; BSA: bovine serum albumin; CBS: cystathionine beta-synthase; CDK7: cyclin dependent kinase 7; CDKN1A: cyclin dependent kinase inhibitor 1A; EGFP: enhanced green fluorescent protein; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GST: glutathione S transferase; H2AX/H2AFX: H2A.X variant histone; HBSS: Hanks balanced salt solution; IP: immunopurification; IR: ionizing radiation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP3K9: mitogen-activated protein kinase kinase kinase 9; mRFP: monomeric red fluorescent protein; mCh: mCherry; MCM7: minichromosome maintenance complex component 7; MTORC1: mechanistic target of rapamycin kinase complex 1; NHEJ: non-homologous end joining; NRBP2: nuclear receptor binding protein 2; NTC: non-targeting control; NUAK1: NUAK family kinase 1; PBS: phosphate-buffered saline; PIK3AP1: phosphoinositide-3-kinase adaptor protein 1; PIK3CA: phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha; PIKK: phosphatidylinositol 3-kinase-related kinase; PRKAA: protein kinase AMP-activated catalytic subunit alpha; PRKAB: protein kinase AMP-activated non-catalytic subunit beta; PRKAG: protein kinase AMP-activated non-catalytic subunit gamma; PRKDC: protein kinase, DNA-activated, catalytic subunit; RLuc: Renilla luciferase; RPS6KB1: ribosomal protein S6 kinase B1; SQSTM1: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TP53: tumor protein p53; TSKS: testis specific serine kinase substrate; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; WT: wild type.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2019.1710430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386596PMC
October 2020

Follow-up strategies following completion of primary cancer treatment in adult cancer survivors.

Cochrane Database Syst Rev 2019 11 21;2019(11). Epub 2019 Nov 21.

Danish Cancer Society Research Center, Survivorship Unit, Strandboulevarden 49, Copenhagen, Central Denmark Region, Denmark, 2100.

Background: Most cancer survivors receive follow-up care after completion of treatment with the primary aim of detecting recurrence. Traditional follow-up consisting of fixed visits to a cancer specialist for examinations and tests are expensive and may be burdensome for the patient. Follow-up strategies involving non-specialist care providers, different intensity of procedures, or addition of survivorship care packages have been developed and tested, however their effectiveness remains unclear.

Objectives: The objective of this review is to compare the effect of different follow-up strategies in adult cancer survivors, following completion of primary cancer treatment, on the primary outcomes of overall survival and time to detection of recurrence. Secondary outcomes are health-related quality of life, anxiety (including fear of recurrence), depression and cost.

Search Methods: We searched CENTRAL, MEDLINE, Embase, four other databases and two trials registries on 11 December 2018 together with reference checking, citation searching and contact with study authors to identify additional studies.

Selection Criteria: We included all randomised trials comparing different follow-up strategies for adult cancer survivors following completion of curatively-intended primary cancer treatment, which included at least one of the outcomes listed above. We compared the effectiveness of: 1) non-specialist-led follow-up (i.e. general practitioner (GP)-led, nurse-led, patient-initiated or shared care) versus specialist-led follow-up; 2) less intensive versus more intensive follow-up (based on clinical visits, examinations and diagnostic procedures) and 3) follow-up integrating additional care components relevant for detection of recurrence (e.g. patient symptom education or monitoring, or survivorship care plans) versus usual care.

Data Collection And Analysis: We used the standard methodological guidelines by Cochrane and Cochrane Effective Practice and Organisation of Care (EPOC). We assessed the certainty of the evidence using the GRADE approach. For each comparison, we present synthesised findings for overall survival and time to detection of recurrence as hazard ratios (HR) and for health-related quality of life, anxiety and depression as mean differences (MD), with 95% confidence intervals (CI). When meta-analysis was not possible, we reported the results from individual studies. For survival and recurrence, we used meta-regression analysis where possible to investigate whether the effects varied with regards to cancer site, publication year and study quality.

Main Results: We included 53 trials involving 20,832 participants across 12 cancer sites and 15 countries, mainly in Europe, North America and Australia. All the studies were carried out in either a hospital or general practice setting. Seventeen studies compared non-specialist-led follow-up with specialist-led follow-up, 24 studies compared intensity of follow-up and 12 studies compared patient symptom education or monitoring, or survivorship care plans with usual care. Risk of bias was generally low or unclear in most of the studies, with a higher risk of bias in the smaller trials. Non-specialist-led follow-up compared with specialist-led follow-up It is uncertain how this strategy affects overall survival (HR 1.21, 95% CI 0.68 to 2.15; 2 studies; 603 participants), time to detection of recurrence (4 studies, 1691 participants) or cost (8 studies, 1756 participants) because the certainty of the evidence is very low. Non-specialist- versus specialist-led follow up may make little or no difference to health-related quality of life at 12 months (MD 1.06, 95% CI -1.83 to 3.95; 4 studies; 605 participants; low-certainty evidence); and probably makes little or no difference to anxiety at 12 months (MD -0.03, 95% CI -0.73 to 0.67; 5 studies; 1266 participants; moderate-certainty evidence). We are more certain that it has little or no effect on depression at 12 months (MD 0.03, 95% CI -0.35 to 0.42; 5 studies; 1266 participants; high-certainty evidence). Less intensive follow-up compared with more intensive follow-up Less intensive versus more intensive follow-up may make little or no difference to overall survival (HR 1.05, 95% CI 0.96 to 1.14; 13 studies; 10,726 participants; low-certainty evidence) and probably increases time to detection of recurrence (HR 0.85, 95% CI 0.79 to 0.92; 12 studies; 11,276 participants; moderate-certainty evidence). Meta-regression analysis showed little or no difference in the intervention effects by cancer site, publication year or study quality. It is uncertain whether this strategy has an effect on health-related quality of life (3 studies, 2742 participants), anxiety (1 study, 180 participants) or cost (6 studies, 1412 participants) because the certainty of evidence is very low. None of the studies reported on depression. Follow-up strategies integrating additional patient symptom education or monitoring, or survivorship care plans compared with usual care: None of the studies reported on overall survival or time to detection of recurrence. It is uncertain whether this strategy makes a difference to health-related quality of life (12 studies, 2846 participants), anxiety (1 study, 470 participants), depression (8 studies, 2351 participants) or cost (1 studies, 408 participants), as the certainty of evidence is very low.

Authors' Conclusions: Evidence regarding the effectiveness of the different follow-up strategies varies substantially. Less intensive follow-up may make little or no difference to overall survival but probably delays detection of recurrence. However, as we did not analyse the two outcomes together, we cannot make direct conclusions about the effect of interventions on survival after detection of recurrence. The effects of non-specialist-led follow-up on survival and detection of recurrence, and how intensity of follow-up affects health-related quality of life, anxiety and depression, are uncertain. There was little evidence for the effects of follow-up integrating additional patient symptom education/monitoring and survivorship care plans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD012425.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870787PMC
November 2019

Psychological stress in long-term testicular cancer survivors: a Danish nationwide cohort study.

J Cancer Surviv 2020 02 21;14(1):72-79. Epub 2019 Nov 21.

Department of Oncology, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark.

Purpose: Long-term cancer survivors may develop psychological late effects. The aim of the present study was to determine prevalence of high level of stress in testicular cancer survivors (TCS) compared with the general population and prevalence of high level of stress among TCS stratified by type of treatment (surveillance, bleomycin, etoposide and cisplatin (BEP), or abdominal radiotherapy (RT)).

Methods: In this large, nationwide and population-based, cross-sectional study, a total of 2252 TCS filled in a questionnaire between 2014-2016 covering psychological stress (Perceived Stress Scale (PSS)), sociodemographic factors, and physical health variables. Results were compared with a reference population. The reference population consisted of 61,927 men without prior or present cancer and sampled at random from the central population. High level of stress was defined as a PSS score ≥ 16, equivalent to the highest scoring quintile in the reference population. Logistic regression models adjusted for relevant covariates were used to estimate prevalence ratios of high level of stress.

Results: Distribution of TCS was: surveillance, n = 1134; BEP, n = 807; and RT, n = 311 (median time since diagnosis was 19 years). TCS were more likely to have high level of stress compared to the reference population with a prevalence ratio of 1.56 (95% CI, 1.40-1.73). Individually, surveillance, BEP and RT groups had higher level of stress compared to the reference population.

Conclusions: TCS are more likely to have high level of stress. Screening programs for psychological stress should be considered as part of the follow-up program.

Implications For Cancer Survivors: A higher level of stress is observed in TCS irrespective of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11764-019-00835-0DOI Listing
February 2020

Prevalence and risk of occult cancer in stroke.

Acta Neurol Scand 2020 Mar 23;141(3):204-211. Epub 2019 Nov 23.

Danish Cancer Society Research Center, Copenhagen, Denmark.

Objectives: Cancer is associated with higher risk of stroke. Whether this translates into higher risk of cancer in stroke of an extent calling for cancer screening in stroke is unclear. We investigated prevalence and risk of occult cancer in stroke compared to the background population without history of stroke.

Materials And Methods: All patients >40 years of age with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n = 85 893) and matched 1:10 on age and sex to the Danish background population without history of stroke (n = 858 740). Linking data to the Danish Cancer Registry, we determined prevalence of occult cancer in stroke defined as the event of previously unknown cancer during a 1-year follow-up in the stroke and in the background population. Cox regression models were used to study risk in comparison to the background population.

Results: Prevalence (per 1000) of occult cancer in the stroke/background cohorts was 25.0/15.8 in women and 29.8/20.4 in men. Prevalence was dependent on age and sex. Highest among stroke patients aged 70-80 years (35.6 in women, 42.4 in men); lowest in patients aged 40-50 years (8.3 in women, 6.8 in men). Stroke was associated with an overall 54% higher risk of occult cancer but risk increased significantly with smoking, hazard ratio (HR) 1.47, age HR 1.27 per 10 years, male sex HR 1.25, and diabetes HR 1.25.

Conclusions: Prevalence and risk of occult cancer in stroke is considerable and calls for attention when designing the stroke investigation program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13192DOI Listing
March 2020

Educational level and first-time PSA testing in general practice.

Scand J Urol 2019 Oct 30;53(5):275-281. Epub 2019 Oct 30.

Survivorship Unit, Danish Cancer Society Research Center, Copenhagen, Denmark.

Different patterns in the use of prostate-specific antigen (PSA) testing might explain socioeconomic differences in prostate cancer incidence and mortality. We examined the association between socioeconomic position, measured as education and first-time PSA testing in general practice. A population-based cohort study of men aged 45-79 years without prior prostate cancer diagnosis living in the Capital Region of Denmark between 2000 and 2014. Information on socioeconomic indicators (education, income, cohabitation status and work market affiliation), prostate cancer diagnoses, and vital status were obtained from national registries. Date of first PSA test was obtained from the Copenhagen Primary Care Laboratory database. Temporal trends of PSA testing were calculated as annual age-standardised incidence rates and the association was examined by a multivariable Cox proportional hazards model. The cohort consists of 431,997 men of which 105,476 (24%) had a first-time PSA test in the study period. Men with longer education, higher income, living with a partner, and employed had higher rates of PSA testing. For men with short education, the rate of PSA test was 28.3 tests per 1000 person-years compared to 31.2 tests among men with long education. The fully adjusted hazard ratio for a first PSA test among men with short education was 0.87 (95% CI, 0.85-0.89) compared to men with long education. The association between education and first-time PSA testing indicates socioeconomic disparities in health care utilisation, which could explain part of the observed socioeconomic difference in prostate cancer incidence and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2019.1681503DOI Listing
October 2019

Social Inequality by Income in Short- and Long-Term Cause-Specific Mortality after Stroke.

J Stroke Cerebrovasc Dis 2019 Jun 28;28(6):1529-1536. Epub 2019 Mar 28.

Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark. Electronic address:

Goals: It is unclear whether social inequality exists for mortality after stroke. Results of studies on the relation between socioeconomic position (SEP) and mortality after stroke have been inconsistent and inconclusive.

Material And Methods: We studied the association between SEP expressed by income and the risk of death after stroke by merging data on incident stroke from Danish registries with nationwide coverage. We identified all incident cases of stroke hospitalized in Denmark 2003-2012 (n = 60503). Patients were followed up to 9 years after stroke (median 2.6 years). Adjusting for age and sex we studied all-cause death and cause-specific death by stroke, cardiac disease, cancer, and other diseases certified by death records and stratified by income.

Results: Of the patients 20,953 (34.6%) had died within follow-up: Death by stroke 8018 (13.2%); cardiac disease 4250 (7.0%); cancer 3060 (5.0%); other diseases 5625 (9.2%). Long-term mortality rates were inversely related to income for all causes of death. The difference in mortality between the lowest and the highest income group at 5 years after stroke was 15.5% (relative) and 5.7% (absolute). Differences in short-term mortality (1-month to 1-year) between income groups were small and clinically insignificant.

Conclusions: Social inequality in mortality after stroke expressed by income was pronounced for long-term mortality while not for short-term mortality. It seems that social inequality is expressed in a greater risk among stroke patients with low income for the advent of new diseases subsequently leading to death rather than in their ability to survive the incident stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.013DOI Listing
June 2019

Endocrine Late Effects in Survivors of Cancer in Adolescence and Young Adulthood: A Danish Population-Based Cohort Study.

JAMA Netw Open 2018 06 1;1(2):e180349. Epub 2018 Jun 1.

Survivorship Unit, Danish Cancer Society Research Center, Copenhagen, Denmark.

Importance: As survival rates from cancer have improved dramatically over the last decades, there is a need to explore the long-term consequences. Adolescents and young adults with cancer are at risk for several therapy-related late effects; however, these have not been studied extensively.

Objective: To investigate the lifetime risks of endocrine late effects of cancer and cancer treatment in adolescent and young adult cancer survivors.

Design, Setting, And Participants: This Danish, nationwide, population-based cohort study was conducted from January 1, 1976, through December 31, 2009, and included follow-up from January 1, 1977, through December 31, 2010. A total of 32 548 one-year cancer survivors diagnosed at ages 15 to 39 years were identified using the Danish Cancer Registry and 188 728 cancer-free comparison participants matched by year of birth and sex were randomly chosen from the Danish Civil Registration system. Analyses were performed from July 3, 2015, to February 27, 2018.

Exposures: Individuals in the survivor cohort were diagnosed with a first primary cancer at ages 15 to 39 years and received treatment according to recommendations and guidelines at time of diagnosis.

Main Outcomes And Measures: By linkage to the National Patient Register, all hospital contacts for endocrine diseases were identified, and standardized hospitalization rate ratios (RRs) and absolute excess risks (AERs) were calculated.

Results: A total of 32 548 adolescent and young adult 1-year cancer survivors (14 021 [43.1%] male) in the Danish Patient Registry were followed up for 379 157 person-years (median [range]: 10 [0-34] years) and 188 728 cancer-free participants (82 669 [43.8%] male) for comparison were followed up for 2 958 994 person-years (median [range]: 15 [0-34] years). A total of 2129 survivors (6.5%) had at least 1 hospital contact for an endocrine disease, while 1232.0 (3.8%) were expected, yielding a statistically significant increased RR of 1.73 (95% CI, 1.65-1.81). The RRs were highest for testicular hypofunction (75.12; 95% CI, 45.99-122.70), ovarian hypofunction (14.65; 95% CI, 8.29-25.86), and pituitary hypofunction (11.14; 95% CI, 8.09-15.34). The leading reasons for hospital contacts were thyroid disease (38.0% of total AER), testicular dysfunction (17.1% of total AER), and diabetes (14.4% of total AER). Leukemia survivors were at a high risk for any endocrine disease (RR, 3.97; 95% CI, 3.10-5.09), while Hodgkin lymphoma survivors (RR, 3.06; 95% CI, 2.62-3.57) had the highest disease-specific excess risk for hypothyroidism (AER, 362 per 100 000 person-years; 95% CI, 280-443 per 100 000 person-years).

Conclusions And Relevance: The increased risk for endocrine diseases in adolescent and young adult cancer survivors indicates the need for counseling and follow-up, and could guide future preventive measures and surveillance strategies. Additional studies are required to determine exact associations between treatment regimens and endocrine diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2018.0349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324403PMC
June 2018

National incidence and survival of patients with non-invasive papillary urothelial carcinoma: a Danish population study.

Scand J Urol 2018 Oct - Dec;52(5-6):364-370. Epub 2018 Nov 1.

a Department of Urology, Herlev and Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.

Objective: To estimate national relative survival of low and high grade non-invasive papillary urothelial carcinoma (Ta LG and Ta HG) and urothelial carcinoma in situ (CIS).

Materials And Methods: All Danish citizens (17,941 patients) with a primary urothelial bladder tumour diagnosis in the period 2000- 2010 were followed until 1 January 2016 and recorded in the Danish Bladder Cancer Cohort database. Survival was compared to the background population matched on age and gender and adjusted by civil status, income, education, and comorbidity.

Results: Patients treated in daily practice with Ta LG have 46% (HR = 1.46 (1.42-1.51) p < 0.001) higher risk of death compared to a background population matched for age and gender. This risk of death ceases to 28% (HR = 1.28 (1.24-1.32) p < 0.001) after adjustment for civil status, income, education, and comorbidity. Relative survival of Ta LG patients is 0.94 (0.93-0.95). These estimates are constant throughout the observation period. Significantly higher mortality is found for patients with Ta HG and CIS, but, in contrast to Ta LG, the relative risk of death of Ta HG (HR = 1.79 (1.69-1.90) p < 0.001) and CIS (HR = 2.02 (1.79-2.26) p < 0.001) decreases considerably after 5 years survival (HR = 1.43 (1.30-1.57) p < 0.001 and HR = 1.64 (1.36-1.98) p < 0.001, respectively).

Conclusion: Patients with Ta LG have a continuous lower survival and a 28% higher risk of death at any time compared to a matched background population when treated in daily practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2018.1518926DOI Listing
August 2019

Prognostic Significance of HPV and p16 Status in Men Diagnosed with Penile Cancer: A Systematic Review and Meta-analysis.

Cancer Epidemiol Biomarkers Prev 2018 10 9;27(10):1123-1132. Epub 2018 Jul 9.

Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.

It has been shown that human papillomavirus (HPV) and p16 status has prognostic value in some HPV-associated cancers. However, studies examining survival in men with penile cancer according to HPV or p16 status are often inconclusive, mainly because of small study populations. The aim of this systematic review and meta-analysis was to examine the association between HPV DNA and p16 status and survival in men diagnosed with penile cancer. Multiple electronic databases were searched. Twenty studies were ultimately included and study-specific and pooled HRs of overall survival and disease-specific survival (DSS) were calculated using a fixed effects model. In the analysis of DSS, we included 649 men with penile cancer tested for HPV (27% were HPV-positive) and 404 men tested for p16 expression (47% were p16-positive). The pooled HR of DSS was 0.61 [95% confidence interval (CI), 0.38-0.98], and the pooled HR of DSS was 0.45 (95% CI, 0.30-0.69). In conclusion, men with HPV or p16-positive penile cancer have a significantly more favorable DSS compared with men with HPV or p16-negative penile cancer. These findings point to the possible clinical value of HPV and p16 testing when planning the most optimal management and follow-up strategy. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-18-0322DOI Listing
October 2018

Risk of Ischemic and Hemorrhagic Strokes in Occult and Manifest Cancers.

Stroke 2018 07 4;49(7):1585-1592. Epub 2018 Jun 4.

Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark (T.S.O.).

Background And Purpose: Manifest cancer is associated with increased risk of stroke. The risk of stroke in people with occult cancer in comparison to the risk in the background population without cancer has not been investigated. Smoking is a risk factor for both cancer and stroke, but the role of smoking for the risk of stroke in cancer has not been investigated.

Methods: We identified all incident cases of cancer in Denmark 2003 to 2012 (n=264.376) from the Danish Cancer Registry. Each person with cancer was matched by age, sex, and income with 10 randomly selected persons without cancer at index date (n=2.571.260). Linking data to the Danish Stroke Registry, we studied risk of ischemic/hemorrhagic stroke the year before (occult cancer) and after cancer diagnosis was established in the Danish Stroke Registry (manifest cancer) and stratified into the 15 most common cancer types related (lung, colon, bladder, rectum, pancreas, kidney, stomach, and head and neck cancer) and unrelated (non-Hodgkin lymphoma, breast, prostate, melanoma, central nervous system, ovary and endometrial) to smoking.

Results: Risk of ischemic/hemorrhagic stroke was increased for both occult (relative risk, 1.75/2.00) and manifest cancers (relative risk, 1.30/1.41). For occult cancer, risk of ischemic stroke was increased for all of the smoking-related cancers, but among cancers unrelated to smoking, only lymphoma, central nervous system, and endometrial cancer were associated with increased risk of stroke; breast, prostate, melanoma, and ovarian cancers were not. For occult cancer, risk of hemorrhagic stroke was generally increased for smoking-related cancers while not for cancers unrelated to smoking. For manifest cancer, risk of ischemic and hemorrhagic stroke was generally increased for cancers related to smoking while not for cancers unrelated to smoking.

Conclusions: Cancer, occult and manifest, is associated with increased risks for stroke. The increased risk is linked mainly to cancers related to smoking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.118.021373DOI Listing
July 2018

Socioeconomic Factors and Ninth Grade School Performance in Childhood Leukemia and CNS Tumor Survivors.

JNCI Cancer Spectr 2018 Jan 25;2(1):pky003. Epub 2018 Apr 25.

Unit of Statistics, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark.

Background: Childhood cancer survivors can experience deficits in school performance in adolescence. Few studies have investigated how social and socioeconomic factors influence and modify school performance. This study investigates the hypothesis that social and parental socioeconomic factors influence ninth grade school performance in childhood leukemia and central nervous system (CNS) tumor survivors and that the effect is different from that in healthy peers.

Methods: We analyzed data from nationwide Danish registers on school grades for children who finished ninth grade during 2002-2015 in Denmark. Using a unique within-school matched design, we compared grades from childhood cancer survivors with grades from healthy peers. Social factors were maternal/paternal civil status, immigrant status, and country of origin. Parental socioeconomic factors were measured by education and income. The study consisted of 36 426 children, of whom 460 and 289 were leukemia and CNS tumor survivors, respectively.

Results: School grades varied considerably across social strata. However, the grades among CNS tumor survivors varied notably less in the following effect modifiers: parental educational attainment, income, and immigrant status. On the contrary, no significant effect modifiers were found among leukemia survivors as compared with healthy peers.

Conclusion: There is a strong effect of social and parental socioeconomic factors on school performance in healthy adolescence in Denmark. The same pattern is seen in survivors of leukemia, but a different pattern is seen in survivors of CNS tumors. This finding suggests that impairment of school-related functions differ between leukemia and CNS tumor survivors. This study contributes to knowledge on learning in adolescence in childhood cancer survivors by investigating several social and socioeconomic effect modifiers with nationwide register data and a unique statistical method particularly suitable for comparing school grades. Improved insight could make it possible to identify high-risk groups that may need different means of help.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jncics/pky003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649790PMC
January 2018

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4.

Nature 2017 12 6;552(7684):194-199. Epub 2017 Dec 6.

Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.

Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing effects as NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature25016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730499PMC
December 2017

Measuring childhood cancer late effects: evidence of a healthy survivor effect.

Eur J Epidemiol 2017 12 28;32(12):1089-1096. Epub 2017 Nov 28.

Department of Pediatrics, Aarhus University Hospital, Århus, Denmark.

Introduction: Given considerable focus on health outcomes among childhood cancer survivors, we aimed to explore whether survivor bias is apparent during long-term follow-up of childhood cancer survivors.

Methods: We identified all 1-year survivors of cancer diagnosed before 20 years of age in Denmark, Finland, Iceland, and Sweden. From the general population, we randomly sampled a comparison cohort. Study individuals were followed for hospitalizations for diseases of the gastroenterological tract, endocrine system, cardiovascular system, or urinary tract from the start of the cancer registries to 2010. We estimated cumulative incidence with death as competing risk and used threshold regression to compare the hazards of the diseases of interest at ages 20, 40, 60, and 75 years.

Results: Our study included 27,007 one-year survivors of childhood cancer and 165,620 individuals from the general population. The cumulative incidence of all four outcomes was higher for childhood cancer survivors during early adulthood, but for three outcomes, the cumulative incidence was higher for the general population after age 55 years. The hazard ratios (HRs) decreased for all outcomes with increasing age, and for two of the outcomes, the hazards were higher for the general population at older ages (endocrine diseases: age-specific HRs = 3.0, 1.4, 1.0, 0.87; Cardiovascular diseases: age-specific HRs = 4.1, 1.4, 0.97, 0.84).

Conclusions: Our findings provide empirical evidence that survivor bias attenuates measures of association when comparing survivors with the general population. The design and analysis of studies among childhood cancer survivors, particularly as this population attains older ages, should account for survivor bias to avoid misinterpreting estimates of disease burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10654-017-0305-4DOI Listing
December 2017

Does HPV status influence survival after vulvar cancer?

Int J Cancer 2018 03 16;142(6):1158-1165. Epub 2017 Nov 16.

Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.

High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I statistic was used to describe heterogeneity. The studies included a total of 1,638 women with HPV tested vulvar cancers of which 541 and 1,097 were HPV-positive and HPV-negative, respectively. Fifteen studies included only squamous cell carcinomas. We found a pooled HR of 0.61 (95% CI: 0.48-0.77) and 0.75 (95% CI: 0.57-1.00) for 5-year OS and DFS, respectively. Across study heterogeneity was moderate to high (OS: I  = 51%; DFS: I  = 73%). In conclusion, women with HPV-positive vulvar cancers have a superior survival compared to women with HPV-negative, which could be of great clinical interest and provides insight into the differences in the natural history of HPV-positive and negative vulvar cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.31139DOI Listing
March 2018

The Prognostic Value of AJCC Staging in Uveal Melanoma Is Enhanced by Adding Chromosome 3 and 8q Status.

Invest Ophthalmol Vis Sci 2017 02;58(2):833-842

Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.

Purpose: The American Joint Committee on Cancer (AJCC) staging system has been validated for use as a prognostic parameter in uveal melanoma (UM). We studied whether adding information regarding chromosome 3 and 8q status further enhances the prognostic value of this staging system.

Methods: We retrospectively studied a cohort of 522 patients who had been treated for UM in two different centers between 1999 and 2015. The mean follow-up time was 47.7 months. Cumulative incidence curves were generated and regression analyses were performed for different combinations of AJCC staging and chromosome status. Death due to UM metastases was the primary endpoint.

Results: In AJCC stage I cases, only patients with monosomy 3 as well as chromosome 8q gain died due to UM metastases (P < 0.001). Among patients with stage II and III tumors, those with monosomy 3 plus gain of chromosome 8q had the worst prognosis, whereas the clinical outcome of those with only one of these aberrations was intermediate (P < 0.001). Patients without monosomy 3 and 8q gain showed favorable prognosis, independent of their tumor's AJCC stage. In cases with monosomy 3, 8q gain, or both, adding AJCC stage improved the predictive value. Multivariable regression analyses demonstrated that AJCC staging and chromosome 3 and 8q status contain independent information about survival status.

Conclusions: Combining information on AJCC staging and chromosome 3 and 8q status allows a more accurate prognostication in UM. We conclude that the prognostic value of the AJCC staging system can be improved by adding information regarding chromosome 3 and 8q status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.16-20212DOI Listing
February 2017

Progressive strength training to prevent LYmphoedema in the first year after breast CAncer - the LYCA feasibility study.

Acta Oncol 2017 Feb 13;56(2):360-366. Epub 2017 Jan 13.

a Survivorship Unit , Danish Cancer Society Research Center , Copenhagen , Denmark.

Background: Lymphoedema is a common late effect after breast cancer (BC) that has no effective cure once chronic. Accumulating evidence supports progressive strength training (PRT) as a safe exercise modality in relation to the onset and exacerbation of lymphoedema. In the 'preventive intervention against LYmphoedema after breast CAncer' (LYCA) feasibility study we examined the feasibility of a program of PRT in the first year after BC to inform a planned randomised controlled trial (RCT).

Material And Methods: LYCA was a one-group prospective pilot trial inviting women operated with axillary lymph node dissection for unilateral primary BC. Participants exercised three times a week for 50 weeks (20 weeks supervised followed by 30 weeks home-based exercise). The program ensured slow individualised progression during the exercise program. The primary outcome was feasibility measured by eligibility and recruitment rates, as well as questionnaire-assessed satisfaction and adherence to exercise. Furthermore, we assessed arm interlimb volume difference by water displacement, muscle strength by dynamic and isometric muscle testing and range of movement in the shoulder by goniometry.

Results: In August 2015, eight of 11 eligible patients accepted participation. Two of them dropped out early due to other health issues. The remaining six participants had high exercise adherence through the supervised period, but only three maintained this through the home exercise period. Program satisfaction was high and no serious adverse events from testing or exercising were reported. One participant presented with lymphoedema at 50-week follow-up. Muscle strength markedly increased with supervised exercise, but was not fully maintained through the home exercise period. Range of shoulder movement was not negatively affected by the program.

Conclusion: Recruitment, testing, and exercise in LYCA was safe and feasible. At the 50-week follow-up, there was one case of lymphoedema. The LYCA program will be further tested in a full-scale RCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2016.1268266DOI Listing
February 2017

Ninth grade school performance in Danish childhood cancer survivors.

Br J Cancer 2017 01 12;116(3):398-404. Epub 2017 Jan 12.

Unit of Cancer Survivorship, Childhood Cancer Survivorship Research Group, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen 2100, Denmark.

Background: Childhood cancer survivors can experience learning problems resulting in lower-than-expected attained education as adults. It is unclear whether learning problems manifest already during adolescence.

Methods: We analysed nationwide Danish registries on school grades for Danish children during 2001-2014. Applying a matched design we compared grades of childhood cancer survivors to children without cancer at ninth grade. We estimated grade differences by subject and its correlation to cancer site and age at diagnosis. The available statistical precision allowed for an analysis of more rare cancer sites.

Results: The total study population was 793 332 children (mean age 15.24 years and 49.7% girls), of whom 1320 were childhood cancer survivors. Lower rank grades were seen in children with cancer in all school subjects but differed substantially according to cancer site. Most affected were survivors of central nervous system (CNS) tumours, neuroblastoma, lymphoma, leukaemia, other malignant neoplasm and germ-cell tumours. Survivors from other cancer types did not obtain lower grades. Lower rank grades were associated with young age at diagnosis.

Conclusions: The effect of childhood cancer differed substantially between cancer sites. The largest effect was among survivors of CNS tumours and leukaemia diagnosed at a young age, suggesting an association with radiation therapy. However, the majority of cancer survivors fare well. Increasing awareness on children affected by cancer and special accommodations may help maximise the learning potential of those most affected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/bjc.2016.438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294489PMC
January 2017

Long-term Exposure to Fine Particulate Matter and Breast Cancer Incidence in the Danish Nurse Cohort Study.

Cancer Epidemiol Biomarkers Prev 2017 03 2;26(3):428-430. Epub 2016 Dec 2.

Research Center for Prevention and Health, Capital Region of Denmark, Rigshospitalet - Glostrup, University of Copenhagen, Glostrup, Denmark.

An association between air pollution and breast cancer risk has been suggested, but evidence is sparse and inconclusive. We included 22,877 female nurses from the Danish Nurse Cohort who were recruited in 1993 or 1999 and followed them for incidence of breast cancer ( = 1,145) until 2013 in the Danish Cancer Register. We estimated annual mean concentrations of particulate matter with diameter <2.5 μg/m (PM) and <10 μg/m (PM), and nitrogen dioxide (NO) at nurses' residences since 1990 using an atmospheric chemistry transport model. We examined the association between the 3-year running mean of each pollutant and breast cancer incidence using a time-varying Cox regression. We found no association between breast cancer and PM (HR, 0.99; 95% confidence interval, 0.94-1.10 per interquartile range of 3.3 μg/m), PM (1.02; 0.94-1.10 per 2.9 μg/m), or NO (0.99; 0.93-1.05 per 7.4 μg/m). Air pollution is not associated with breast cancer risk. Exposure to air pollution in adulthood does not increase the risk of breast cancer, but more data on the effects of early exposure, before first birth, are needed. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-16-0578DOI Listing
March 2017

Long-term exposure to ambient air pollution and incidence of brain tumours: The Danish Nurse Cohort.

Neurotoxicology 2016 07 2;55:122-130. Epub 2016 Jun 2.

Centre for Epidemiology and Screening, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: Air pollution has been considered a potent environmental risk factor for neuropathology through neuroinflammation and oxidative stress, which might also cause brain tumour formation. However, epidemiological evidence on the association between air pollution and brain tumours in humans is sparse, with no data on exposure to particles. In this study we aim to examine associations between long-term exposure to ambient air pollution and risk for development of brain tumours.

Methods: We used the Danish Nurse Cohort with 28,731 female nurses (age≥44years) recruited in 1993 or 1999 when self-reported information on lifestyle was collected. We obtained data on the incidence of brain tumours until 2013 from the Danish Cancer Register, and estimated annual mean concentrations of particulate matter with diameter<2.5μm (PM2.5), particulate matter with diameter<10μm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at the residence since 1990 using an atmospheric integrated chemistry-transport models system, and examined the association between the 3-year running mean of pollutants and brain tumour incidence using time-varying Cox regression, separately for total brain tumours, and for tumour subtypes by location (brain or meninges), and by malignancy (malignant or benign), and estimated hazard ratios and 95% confidence intervals per increase in interquartile range of exposure.

Results: Of 25,143 tumour-free nurses at recruitment, 121 developed brain cancer during 15.7 years of follow-up. We found a weak positive association between total brain tumours and PM2.5 (1.06; 0.80-1.40 per 3.37μg/m(3)), NO2 (1.09; 0.91-1.29) per 7.5μg/m(3), and NOx (1.02; 0.93-1.12 per 10.22μg/m(3)), and none with PM10 (0.93; 0.70-1.23 per 3.31μg/m(3)). Associations with PM2.5 and NO2 were stronger for tumours located in meninges than in brain, and for benign than for malignant tumours. Finally, association of total brain tumours with PM2.5 was modified by BMI, and was statistically significantly enhanced in obese women (2.03; 1.35-3.05).

Conclusion: We found weak evidence for association between risk of brain tumours and long-term exposure to air pollution in women older than 44 years. However, we present novel results that obese women may be susceptible, as well as a positive tendency towards elevated risk for meninges and benign tumours, which require further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuro.2016.06.003DOI Listing
July 2016
-->