Publications by authors named "Sara Ekberg"

20 Publications

  • Page 1 of 1

Statin use and survival in 16 098 patients with non-Hodgkin lymphoma or chronic lymphocytic leukaemia treated in the rituximab era.

Br J Haematol 2021 Jul 31. Epub 2021 Jul 31.

Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.

Statin use has been associated with reduced mortality from several cancers but also suggested, in vitro, to diminish the effectiveness of lymphoma treatments including rituximab. The present study aimed to assess the association of statin use with mortality in patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). We identified all incident NHLs and CLLs in Sweden from 2007 to 2013 with subtype information in the Swedish Lymphoma and Cancer Registers. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pre- or post-diagnosis statin use (yes/no, intensity) with lymphoma-specific, cardiovascular, or all-cause mortality; and for follicular lymphoma (FL) by initial treatment strategy (active/watch-and-wait). Among 16 098 incident NHL/CLL patients, 20% used statins at diagnosis. Pre- and post-diagnosis statin use, and statin intensity were not consistently associated with any mortality outcome in patients with NHL, overall or for any subtype. For actively treated patients with FL, statin use did not appear to increase lymphoma-specific mortality (vs. non-users, HR [95% CI] 0·87 [0·45-1·67]). For CLL, statin use was associated with all-cause and cardiovascular but not consistently with lymphoma-specific mortality. In conclusion, statin use was not associated with improved lymphoma survival but appears safe to use during lymphoma treatment.
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http://dx.doi.org/10.1111/bjh.17733DOI Listing
July 2021

Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden.

Blood Cancer J 2021 01 7;11(1). Epub 2021 Jan 7.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

We performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007-2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n = 3550, median age 69 years), whereas 14% did not (n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7-66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7-24.6, n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5-3.6, n = 118) overall, and 8.0% (95% CI: 6.0-10.6, n = 48) among patients with high CNS-IPI (4-6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.
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http://dx.doi.org/10.1038/s41408-020-00403-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791057PMC
January 2021

Concordance in survival among first-degree relatives diagnosed with indolent lymphoid malignancies including chronic lymphocytic leukemia.

Eur J Haematol 2020 Dec 29;105(6):779-785. Epub 2020 Sep 29.

Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.

Objectives: To investigate concordance in survival time among first-degree relatives with lymphoid malignancies.

Methods: By linkage of national Swedish registers, we identified 66 430 patients diagnosed with a lymphoid malignancy 1958-2016 with information on first-degree relationships and follow-up until 2017. Among these, we identified pairs of first-degree relatives with any (N = 3326) or a similar (N = 690) lymphoid malignancy subtype. We defined survival in the first-degree relative as good, expected, or poor based on tertiles of deviance residuals from a multivariable Cox regression model. Next, we used Cox regression to estimate hazard ratios (HR) of death with 95% confidence intervals (CI) among patients, using the survival of their first-degree relative as exposure and adjusting for confounders.

Results: There was no concordance in survival among first-degree relatives with any lymphoid malignancy (HR  = 1.00 (reference), HR  = 1.02, 95% CI: 0.89-1.17, HR  = 1.12, 95% CI: 0.98-1.27, P  = .08). Among first-degree relatives with indolent lymphoma, including chronic lymphocytic leukemia, those with a first-degree relative to an expected or poor survival had worse outcome compared to those with a first-degree relative with good survival (HR  = 1.44, 95% CI: 0.82-2.53, HR  = 1.79, 95% CI: 1.07-3.00, P  = .03).

Conclusion: Our results support a role of inherited factors in the outcome of indolent lymphoma, including chronic lymphocytic leukemia.
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http://dx.doi.org/10.1111/ejh.13510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702025PMC
December 2020

Outcome and determinants of failure to complete primary R-CHOP treatment for reasons other than non-response among patients with diffuse large B-cell lymphoma.

Am J Hematol 2020 07 3;95(7):740-748. Epub 2020 Apr 3.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Patients with diffuse large B-cell lymphoma (DLBCL) who fail to complete planned treatment with R-CHOP due to toxicity are sparsely described. We investigated the extent of failure to complete treatment (six cycles or more, or three cycles + RT for patients with stage I disease) with R-CHOP for reasons unrelated to non-response, the determinants of such failure and the outcome among these patients. Three thousand one hundred and forty nine adult DLBCL patients who started primary treatment with R-CHOP were identified through the Swedish lymphoma register 2007-2014. Of these, 147 (5%) stopped prematurely after 1-3 cycles of R-CHOP for reasons unrelated to non-response, 168 (5%) after 4-5 cycles and 2639 patients (84%) completed planned treatment. Additionally, 195 (6%) patients did not complete treatment due to non-response or death before treatment end. In a multivariable logistic regression model, age > 75 years, poor performance status, extranodal disease and Charlson Comorbidity Index ≥1 were significantly associated with failure to complete planned R-CHOP treatment for other reasons than non-response. Non-completion of treatment strongly correlated with survival. Five-year overall survival for patients who received 1-3 cycles was 26% (95% CI: 19%-33%), 49% (95% CI: 41%-57%) for 4-5 cycles and 76% (74%-77%) for patients who completed treatment. Failure to complete planned R-CHOP treatment is an important clinical issue associated with inferior survival. Old age and poor performance status most strongly predict such failure. These results indicate a need for improved treatment tailoring for patients with certain baseline demographics to improve tolerability and chance for treatment completion.
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http://dx.doi.org/10.1002/ajh.25789DOI Listing
July 2020

Statin use is associated with improved survival in multiple myeloma: A Swedish population-based study of 4315 patients.

Am J Hematol 2020 06 20;95(6):652-661. Epub 2020 Mar 20.

Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.

Statin use has been associated with reduced cancer-specific mortality among patients with several cancer types, including multiple myeloma (MM). We aimed to further elucidate the association of statin use and dose intensity with MM survival. Using Swedish population-based national health registers, we identified all incident MM diagnoses occurring January 1, 2007 to December 31, 2013 and their drug dispensations and comorbidities. We assessed statin exposure in 6-month periods pre- and post-diagnosis, treated diagnosis as baseline for calculating survival time, and calculated hazard ratios (HR) and 95% confidence intervals (CI) of exposure-related MM-specific and all-cause mortality using Cox regression. We assessed statin exposure during the entire follow-up and risk of MM-specific mortality in a nested case-control analysis. We classified dose intensity according to American College of Cardiology/American Heart Association recommendations. We ascertained 4315 MM cases during follow-up. Statin use was associated with reduced MM-specific mortality (pre-diagnosis use multivariate-adjusted HR, 95% CI: 0.83, 0.71-0.96; 6 months post-diagnosis: 0.73, 0.60-0.89; entire follow-up: 0.65, 0.52-0.80) and (more weakly) with all-cause mortality. Intensity analyses suggested a dose-response; MM-specific mortality decreased with increasing statin intensity in all time windows (eg, 6 months post-diagnosis: low [0.76 (0.56-1.03)], medium [0.73 (0.58-0.92)], high [0.33 (0.08-1.32)] intensity). However, relatively few patients received high intensity treatment, and the trend was statistically significant only for unadjusted pre-diagnosis use. In this large population-based MM cohort, statin use was associated with improved MM-specific survival in both sexes. Randomized prospective studies are warranted to evaluate statins as adjuvant treatment in MM.
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http://dx.doi.org/10.1002/ajh.25778DOI Listing
June 2020

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden.

Fertil Steril 2020 03 18;113(3):524-532. Epub 2020 Feb 18.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Objective: To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons.

Design: Nationwide prospective study.

Setting: Sweden.

Patient(s): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection.

Intervention(s): None.

Main Outcome Measures(s): Infant (<1 year) and childhood (1-18 years) mortality.

Result(s): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years.

Conclusion(s): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.
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http://dx.doi.org/10.1016/j.fertnstert.2019.10.018DOI Listing
March 2020

Trends in the prevalence, incidence and survival of non-Hodgkin lymphoma subtypes during the 21st century - a Swedish lymphoma register study.

Br J Haematol 2020 06 17;189(6):1083-1092. Epub 2020 Feb 17.

Clinical Epidemiology Division, Department of Medicin Solna, Karolinska Institutet, Stockholm, Sweden.

Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000-2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors.
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http://dx.doi.org/10.1111/bjh.16489DOI Listing
June 2020

Season of birth, childhood asthma and allergy in a nationwide cohort-Mediation through lower respiratory infections.

Clin Exp Allergy 2020 02 28;50(2):222-230. Epub 2019 Dec 28.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Previous studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or mediated by respiratory tract infections.

Objective: We aimed to estimate the association between season of birth and risk of childhood asthma/wheeze or allergic rhinoconjunctivitis in a population-based setting, and the mediating effect of lower respiratory infections.

Methods: Two population-based cohorts were identified from the nationwide Swedish Medical Birth, Patient and Prescribed Drug Registers. The association between birth month/season and asthma/wheeze incidence was analysed using Cox proportional regression in the younger cohort born 2005-2010 (n = 582 494) and asthma/allergic rhinoconjunctivitis prevalence during the 7th year of life using log-binomial models in the older cohort born 2001-2004 (n = 367 583). Interactions were formally tested. Mediation analyses to address the effect of lower respiratory infections were performed in the older cohort using the R package "medflex."

Results: Children born during fall and winter had an increased risk of asthma/wheeze after 2 years of age in the younger cohort: hazard ratio 1.24 (95% confidence interval, CI 1.17, 1.33) for winter and risk of prevalent asthma during their 7th year of life in the older cohort; prevalence ratio (PR) 1.12 (95% CI 1.08, 1.16) for winter. These estimates were partly mediated by lower respiratory infections; the indirect effect for winter compared with summer was PR 1.03 (95% CI 1.03, 1.04). The association was similar for allergic rhinoconjunctivitis in the 7th year of life, but not mediated by respiratory infections.

Conclusion: We found that the association between season of birth and risk of childhood asthma/wheeze, but not allergic rhinoconjunctivitis, is partly mediated through lower respiratory infections.

Clinical Relevance: This has important implications for patient care, such as asthma management programmes to notify timing of seasonality for viral respiratory tract infections.
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http://dx.doi.org/10.1111/cea.13542DOI Listing
February 2020

Sibship and dispensing patterns of asthma medication in young children-a population-based study.

Pharmacoepidemiol Drug Saf 2019 08 4;28(8):1109-1116. Epub 2019 Jul 4.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Purpose: Our aim was to study the association between sibship and dispensing patterns of asthma medication in young children, focusing on incidence and persistence, and taking sibship status, asthma diagnoses, and siblings' medication into account.

Methods: A register-based cohort study including all children (n = 50 546) born in Stockholm, Sweden 2006 to 2007, followed up during 2006 to 2014. Exposure was sibling status; outcome was incidence of dispensed asthma medication and persistence over time. A Cox model was used to study the association between sibship and asthma medication. Persistence was defined using two different time windows (4 and 18 months) in a refill sequence model including siblings' and unrelated control children's medication.

Results: After 1 year of age, the adjusted hazard ratio of dispensed asthma medication was 0.85 (95% CI 0.80-0.90) among children with siblings compared with singletons. The estimated proportion of children with persistent controller medication was 7.2% (4-month model) and 64.5% (18-month model). When including the siblings' controller medication, the estimated proportion was 8.8% (4 months) and 7.8% for control children (relative risk (RR) 0.89, 95% CI 0.81-0.98). The persistence was lower for those with siblings compared with singletons (adj. RR 0.72, 95% CI 0.62-0.85 for 4 months) with similar estimates for older, younger, and full siblings and regardless of asthma diagnoses.

Conclusions: Siblings have different dispensing patterns of asthma medications compared with singletons regardless of asthma diagnoses. After including the siblings' asthma medication and compared with control children, the proportion of children with persistent medication increased which may indicate that siblings share asthma medications.
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http://dx.doi.org/10.1002/pds.4802DOI Listing
August 2019

No association between low-dose aspirin use and breast cancer outcomes overall: a Swedish population-based study.

Breast Cancer Res 2018 11 20;20(1):142. Epub 2018 Nov 20.

Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet and Karolinska University Hospital, SE-171 76, Stockholm, Sweden.

Background: Results from previous studies indicate that use of low-dose aspirin may improve breast cancer prognosis. We evaluated aspirin use and breast cancer outcomes in relation to clinical characteristics as well as dose and duration of aspirin use.

Methods: We used information from the Regional Breast Cancer Quality-of-Care Registries in three Swedish regions to identify 21,414 women diagnosed with a first stage I-III breast cancer between 1 April 2006 and 31 December 2012. The cohort was further linked to nationwide registers to retrieve information about dispensing low-dose aspirin before and after breast cancer diagnosis, comorbidity and causes of death. In a separate analysis, we investigated time to breast cancer death among 621 women with stage IV disease at diagnosis. Associations were evaluated using a multivariable Cox proportional hazards model.

Results: Among women with stage I-III breast cancer, 2660 (12.4%) used low-dose aspirin shortly before breast cancer diagnosis and 4091 (19.1%) were users during follow-up. Women were followed for a median of 3.8 years after diagnosis. There was no association between aspirin use and breast cancer-specific death in multivariable analyses (use before diagnosis: hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.77-1.12; use after diagnosis: HR 1.00, 95% CI 0.74-1.37). Similarly, aspirin use was not associated with risk of first recurrence/metastases in a subgroup of stage I-III breast cancer patients (HR 0.97, 95% CI 0.86-1.10). However, in analyses stratified by stage, an inverse association between low-dose aspirin use after diagnosis and breast cancer death was found for women with stage I tumors (HR 0.53, 95% CI 0.29-0.96). Among women with stage IV disease at diagnosis, aspirin use was not associated with time to breast cancer death (HR 0.91, 95% CI 0.67-1.23).

Conclusion: In this large population-based cohort study there was no evidence that low-dose aspirin use before or after breast cancer diagnosis is associated with a reduced risk of adverse outcomes overall in breast cancer. However, a potential benefit was noted among women with stage I tumors, warranting further investigation.
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http://dx.doi.org/10.1186/s13058-018-1065-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247765PMC
November 2018

Dog characteristics and future risk of asthma in children growing up with dogs.

Sci Rep 2018 11 15;8(1):16899. Epub 2018 Nov 15.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

There is observational evidence that children exposed to dogs in early life are at lower risk of asthma. It is unknown whether this association is modified by dog characteristics such as sex, breed, number of dogs, and dog size. The aim of this study was to determine whether different dog characteristics modify the risk of asthma among children exposed to dogs during their first year of life. In the main analysis, we used national register data for all children born in Sweden from Jan 1st 2001 to Dec 31st 2004 with a registered dog in the household during their first year of life (n = 23,585). We used logistic regression models to study the association between dog characteristics and the risk of asthma or allergy diagnosis and medication at age six. The prevalence of asthma at age six was 5.4%. Children exposed to female dogs had lower risk of asthma compared to those exposed to male dogs, odds ratio, OR = 0.84 (95% confidence interval, CI 0.74 to 0.95). Children with two dogs or more had lower risk of asthma than those with one dog only, OR = 0.79 (95% CI 0.65 to 0.95). Children whose parents had asthma and allergy had a higher frequency of exposure to dog breeds anecdotally described as "hypoallergenic" compared to those parents without asthma or allergy (11.7% vs 7.6%, p < 0.001). Exposure to these breeds were associated with higher risk of allergy OR = 1.27 (95% CI 1.02 to 1.59) but not asthma. In conclusion, we found evidence of an association between the sex of dog and the number of dogs with a lower risk of childhood asthma in dog-exposed children.
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http://dx.doi.org/10.1038/s41598-018-35245-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237975PMC
November 2018

Long-term survival and loss in expectancy of life in a population-based cohort of 7114 patients with diffuse large B-cell lymphoma.

Am J Hematol 2018 May 17. Epub 2018 May 17.

Division of Clinical Epidemiology, Department of Medicin Solna, Karolinska Institutet, Stockholm, Sweden.

Survival has improved among patients with diffuse large B-cell lymphoma (DLBCL) with the addition of anti-CD20 antibody therapy. We aimed to quantify trends and remaining loss in expectation of life (LEL) due to DLBCL at a national population-based level. Patients diagnosed with DLBCL 2000-2013 (N = 7114) were identified through the Swedish Lymphoma Registry and classified according to the age-adjusted International Prognostic Index (aaIPI). The novel measure LEL is the difference between remaining life years among patients and the general population and was predicted using flexible parametric models from diagnosis and among 2-year survivors, by age and sex. Median age at DLBCL-diagnosis was 70 (18-105) years and 54.8% presented with stage III-IV disease. On average, LEL due to DLBCL decreased from 8.0 (95% CI: 7.7-8.3) to 4.6 (95% CI: 4.5-4.6) years over the study period. By risk group, LEL was most reduced among patients with aaIPI ≥2 aged 50-60 years. However, these patients were still estimated to lose >8 years in 2013 (eg, LEL 8.6 years (95% CI: 5.0-12.3)). Among 2-year survivors, LEL was reduced from 6.1 years (95% CI: 5.6-6.5) (aaIPI ≥ 2) and 3.8 years (95% CI: 3.6-4.1) (aaIPI < 2) to 1.1 (95% CI: 1.1-1.2) and 1.0 year (95% CI: 0.8-1.1), respectively. The reduction was observed across all ages. Results for females were similar. By using LEL we illustrate the improvement of DLBCL survival over time. Despite adequate immunochemotherapy, substantial LEL among patients with IPI ≥ 2 points to remaining unmet medical needs. We speculate that observed reduced losses among 2-year survivors indicate a reduction of late relapses.
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http://dx.doi.org/10.1002/ajh.25147DOI Listing
May 2018

Survival and level of care among breast cancer patients with brain metastases treated with whole brain radiotherapy.

Breast Cancer Res Treat 2017 Dec 22;166(3):887-896. Epub 2017 Aug 22.

Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institute Solna, Karolinska University Hospital, 171 76, Stockholm, Sweden.

Purpose: The benefit of whole brain radiotherapy (WBRT) for late stage breast cancer patients with brain metastases has been questioned. In this study we evaluated survival and level of care (hospital or home) following WBRT in a population-based cohort by personal and tumor characteristics.

Methods: We identified 241 consecutive patients with breast cancer and brain metastases receiving WBRT in Stockholm, Sweden, 1999-2012. Through review of medical records, we collected data on prognostic determinants including level of care before and after WBRT. Survival was estimated using Cox regression, and odds ratios (OR) of not coming home using logistic regression.

Results: Median age at WBRT was 58 years (range 30---88 years). Most patients (n = 212, 88%) were treated with 4 Gray × 5. Median survival following WBRT was 2.9 months (interquartile range 1.1-6.6 months), and 57 patients (24%) were never discharged from hospital. Poor performance status and triple-negative tumors were associated with short survival (WHO 3-4 median survival 0.9 months, HR = 5.96 (3.88-9.17) versus WHO 0-1; triple-negative tumors median survival 2.0 months, HR = 1.87 (1.23-2.84) versus Luminal A). Poor performance status and being hospitalized before WBRT were associated with increased ORs of not coming home whereas cohabitation with children at home was protective.

Conclusion: Survival was short following WBRT, and one in four breast cancer patients with brain metastases could never be discharged from hospital. When deciding about WBRT, WHO score, level of care before WBRT, and the patient's choice of level of care in the end-of-life period should be considered.
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http://dx.doi.org/10.1007/s10549-017-4466-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680371PMC
December 2017

Increased healthcare use up to 10 years among relapse-free Hodgkin lymphoma survivors in the era of intensified chemotherapy and limited radiotherapy.

Am J Hematol 2017 Mar 4;92(3):251-258. Epub 2017 Feb 4.

Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

With today's excellent cure rates for Hodgkin lymphoma (HL), the number of long-term survivors is increasing. This study aims to provide a global assessment of late adverse effects for working-age HL survivors treated with contemporary protocols (combination chemotherapy and limited radiotherapy). From Swedish nationwide registers we identified 1017 HL survivors diagnosed in 2000-2009, aged 18-60 years (median 32) and surviving at least one year post-diagnosis, and 4031 age-, sex-, and calendar-year-matched population comparators. Incidence rate ratios (IRR) and 95% confidence intervals (95%CI) for outpatient visits and inpatient bed-days after the first year up to 14 years post-diagnosis (through 2013) were estimated across treatment subgroups, considering relapse-free time and using negative binomial regression. Scheduled outpatient visits for HL were excluded. The rate of outpatient visits was nearly double (IRR = 1.8, 95%CI: 1.6-2.0) that among comparators and higher rates persisted up to 10 years post-diagnosis. The rate of inpatient bed-days among relapse-free survivors was more than three-fold (IRR = 3.6, 95%CI: 2.7-4.7) that of comparators and the increase persisted up to four years post-diagnosis. Patients requiring 6-8 chemotherapy courses had higher rates of outpatient visits (IRR = 1.4, 95%CI: 1.1-1.7) and bed-days (IRR = 4.7, 95%CI: 2.9-7.8) than patients treated with 2-4 courses + radiotherapy. Previously seldom reported reasons for the excess healthcare use included chest pain, keratitis, asthma, diabetes mellitus, and depression. Contemporary treatment, chemotherapy in particular, was associated with excess healthcare use among HL survivors during the first decade postdiagnosis. The reasons for healthcare visits reflected a wide range of disorders, indicating the need of broad individualized care in addition to specific screening programs.
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http://dx.doi.org/10.1002/ajh.24623DOI Listing
March 2017

Work Loss Duration and Predictors Following Rectal Cancer Treatment among Patients with and without Prediagnostic Work Loss.

Cancer Epidemiol Biomarkers Prev 2016 06 13;25(6):987-94. Epub 2016 Apr 13.

Clinical Epidemiology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.

Background: The number of working-age rectal cancer survivors is increasing due to early detection and improved treatment. However, work loss duration and predictors among them have not been studied thoroughly.

Methods: We identified 3,438 patients with stage I-III rectal cancer, 18 to 61 years of age in the Swedish Colorectal Cancer Register 1996-2009. Information on work loss due to sick leave or disability pension was collected from 2 years before diagnosis to 5 years after (until December 31st, 2013). Incidence rate ratios (IRR) of work loss were estimated in a negative binominal model by clinical characteristics for the 1st and 2nd-5th years after diagnosis. Patients were stratified by prediagnostic work loss.

Results: Patients without prediagnostic work loss (74%) experienced median 147 days (25th and 75th percentile: 55 and 281) of work loss during the 1st year after diagnosis. Work loss rates (2nd-5th years) were significantly increased among relapse-free patients diagnosed in stage III [IRR = 1.92; 95% confidence interval (CI), 1.52-2.43], operated with abdominoperineal resection (IRR = 1.26; 95% CI, 1.03-1.56), and treated with neoadjuvant (chemo)radiotherapy (IRR = 1.46; 95% CI, 1.06-2.02). Patients with prediagnostic work loss (26%) experienced median 336 days (25th and 75th percentile: 183 and 365) of work loss during the 1st year, and rates did not vary clinically till 5 years.

Conclusion: Without prediagnostic work loss, disease- and treatment-related factors could help identify rectal cancer patients in need of early interventions to facilitate return to work.

Impact: Clinical awareness around prediagnostic and postdiagnostic work loss and individualized cancer rehabilitation programs should be emphasized among cancer survivors. Cancer Epidemiol Biomarkers Prev; 25(6); 987-94. ©2016 AACR.
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http://dx.doi.org/10.1158/1055-9965.EPI-16-0112DOI Listing
June 2016

Lost workdays in uterine cervical cancer survivors compared to the general population: impact of treatment and relapse.

J Cancer Surviv 2016 06 12;10(3):514-23. Epub 2015 Nov 12.

Unit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Purpose: The aim of the present study was to examine the risk of lost workdays due to sick leave and disability pension by treatment modality and relapse in a population-based cohort of cervical cancer survivors versus matched comparators.

Methods: We identified 1971 cervical cancer patients aged ≤60 years (median 42) at diagnosis in Sweden 2003-2009 and 9254 population comparators. Information on sociodemographic and clinical characteristics, sick leave, and disability pension was retrieved from nationwide prospective registers. Differences in the annual mean number of lost workdays were calculated by linear regression, and hazard ratios (HRs) of disability pension were calculated by Cox regression analysis, with follow-up through September 2013.

Results: Cervical cancer patients had more lost workdays annually than comparators up to 8 years following diagnosis. Relapse-free patients had more lost workdays than comparators up to 4 years. Risk of disability pension during follow-up was increased among the relapse-free patients treated with hysterectomy (HR 1.8 [95 % confidence interval (CI) 1.1-2.8]), hysterectomy plus chemotherapy and/or radiotherapy (HR 2.5 [95 % CI 1.2-5.4]), or chemotherapy and/or radiotherapy alone (HR 3.0 [95 % CI 1.3-6.8]), compared with the population. Women treated with fertility-sparing surgery did not have more lost workdays than the population beyond the first year and were not at increased risk of disability pension.

Conclusion: We observed a long-standing increased risk of lost workdays among cervical cancer patients, overall, as well as among relapse-free patients.

Implications For Cancer Survivors: Extensive but not limited treatment was associated with increased risk of lost workdays, possibly reflecting an association between treatment side effects and work ability.
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http://dx.doi.org/10.1007/s11764-015-0496-1DOI Listing
June 2016

Long-term survival in young and middle-aged Hodgkin lymphoma patients in Sweden 1992-2009-trends in cure proportions by clinical characteristics.

Am J Hematol 2015 Dec 6;90(12):1128-34. Epub 2015 Oct 6.

Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

Trends in Hodgkin lymphoma (HL) survival among patients treated outside of clinical trials provide real-world benchmark estimates of prognosis and help identify patient subgroups for targeted trials. In a Swedish population-based cohort of 1947 HL patients diagnosed in 1992-2009 at ages 18-59 years, we estimated relative survival (RS), cure proportions (CP), and median survival times using flexible parametric cure models. Overall, the CP was 89% (95% CI: 0.87-0.91) and median survival of the uncured was 4.6 years (95% CI: 3.0-6.3). For patients aged 18-50 years diagnosed after the year 2000, CP was high and stable, whereas for patients of 50-59 years, cure was not reached. The survival of relapse-free patients was similar to that of the general population (RS5-year : 0.99; 95% CI: 0.98-0.99, RS15-year : 0.95; 95% CI: 0.92-0.97). The excess mortality of relapsing patients was 19 times (95% CI: 12-31) that of relapse-free patients. Despite modern treatments, patients with adverse prognostic factors (e.g., advanced stage) still had markedly worse outcomes [CP stage: IIIB 0.82 (95% CI: 0.73-0.89); CP stage: IVB 0.72, (95% CI: 0.60-0.81)] and patients with international prognostic score (IPS) ≥3 had 2.7 times higher excess mortality (95% CI: 1.0-7.0, p = 0.04) than patients with IPS <3. High-risk patients selected for 6-8 courses of BEACOPP (bleomycin, etoposide, doxorubicin, cyclofosphamide, vincristine, procarbazine, prednisone)-chemotherapy had a 15-year relative survival of 87%, (95% CI: 0.80-0.92), whereas the corresponding estimate for patients selected for 6-8 courses of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was 93% (95% CI: 0.88-0.97). These population-based results indicate limited fatal side-effects in the 15-year perspective with contemporary treatments, while the unmet need of effective relapse treatment remains of concern. BEACOPP-chemotherapy was still not sufficient in high-risk HL patients.
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http://dx.doi.org/10.1002/ajh.24184DOI Listing
December 2015

Sick leave and disability pension among Swedish testicular cancer survivors according to clinical stage and treatment.

Acta Oncol 2015 Nov 2;54(10):1770-80. Epub 2015 Apr 2.

e Department of Medicine , Karolinska Institutet, Clinical Epidemiology Unit , Stockholm , Sweden.

Purpose: To investigate if testicular cancer survivors (TCSs) have a higher incidence of work loss compared with the population, accounting for stage, treatment and relapse.

Material And Methods: A cohort of 2146 Swedish TCSs diagnosed 1995-2007 (seminoma n = 926, non-seminoma n = 1220) was identified in the SWENOTECA (Swedish-Norwegian Testicular Cancer Group) register, and matched 1:4 to population comparators. Prospectively recorded work loss data (both before and after diagnosis) were obtained from national registers through September 2013. Adjusted relative risks (RR) and 95% confidence intervals (CI) of sick leave and/or disability pension were calculated annually and overall with Poisson- and Cox regression, censoring at relapse. The mean number of annual work days lost was also estimated.

Results: TCSs were at a modestly increased annual risk of work loss up to the third year of follow-up (RR3rd year 1.25, 95% CI 1.08, 1.43), attributed to a more pronounced risk among extensively treated patients (4 chemotherapy courses: RR3rd year 1.60, 95% CI 1.19, 2.15; > 4 courses: RR3rd year 3.70, 95% CI 2.25, 6.11). Patients on surveillance or limited treatment (radiotherapy, 1-3 chemotherapy courses) did not have an increased risk of work loss beyond the first year. TCSs receiving > 4 chemotherapy courses had higher mean number of annual days of work loss up to the 10th year post-diagnosis, and a five-fold risk of disability pension (RR 5.16, 95% CI 2.00, 10.3).

Conclusion: Extensively treated TCSs, but not those on surveillance or limited treatment, are at increased risk of work loss long-term, not explained by relapse. These patients may benefit from early rehabilitation initiatives.
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http://dx.doi.org/10.3109/0284186X.2015.1020967DOI Listing
November 2015

Familial effects on survival after myocardial infarction: a registry-based sib-pair study.

Eur J Epidemiol 2012 Dec 2;27(12):911-4. Epub 2012 Nov 2.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Nobels väg 12A, Stockholm, Sweden.

The chance of surviving an acute myocardial infarction (MI) has increased greatly but many persons still die as a consequence of MI. We assessed the familiality of suffering fatal MI using Swedish registry data. All 4,239 sib-pairs (n = 8,478) where both siblings had suffered an MI and who were born 1932 or later were identified by matching the Swedish National Patient-, Cause of Death and Multi-Generation registries. The Cox proportional hazards model was used to estimate the association between survival times between sibling who had, or not had, a sibling who died within 28 days of their first MI. The risk estimate was adjusted for year of infarction, age at infarction, sex and county for both siblings. The mortality rate was increased the first 28 days after infarction amongst patients who had a sibling who also died within 28 days of infarction (adjusted Hazard ratio (HR) [95 % confidence interval [95 % CI]: 1.44 [1.18-1.75]). These patients also have a worse long-term survival (adjusted HR [95 % CI]: 1.65 [1.24-2.21]). There appears to be familial effects that influence MI survival. This may have important implications for MI prevention strategies but further studies are required to determine if these effects are due to genetic or environmental factors.
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http://dx.doi.org/10.1007/s10654-012-9741-3DOI Listing
December 2012
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