| 1. |
- Andersson, Therese M. -L., et al.
(author)
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Cancer during pregnancy and the postpartum period : A population-based study
- 2015
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In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 121:12, s. 2072-2077
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Journal article (peer-reviewed)abstract
- BACKGROUNDThe purpose of this study was to assess patterns of cancer occurrence during pregnancy and the postpartum period. METHODSThis was a register-based study using data from the Swedish Multi-Generation Register and the National Cancer Register from 1963 to 2007. Pregnancy-associated cancer (PAC) was defined as a malignancy detected during pregnancy or within 2 years of delivery and was assessed in 7 time windows: pregnancy, trimesters 1-3, 0-6 months, 7-12 months, and second year postpartum. Population incidence rates by 5-year age groups and periods were used to estimate the expected number of PACs for each site. The observed versus the expected (O/E) number of cases was estimated with 95% confidence intervals (CI). RESULTSThe 3 most common malignancies during pregnancy were melanoma (n=232), breast (n=139) and cervical cancer (n=139). With a slightly different rank order, these cancers are also the most common in women of childbearing age. The number of observed cases during pregnancy was lower than expected for all cancers, with a combined O/E ratio for all sites of 0.46 (95% CI, 0.43-0.49). The O/E ratio was close to 1 during all postpartum intervals, including 0-6 months (0.93; 95% CI, 0.88-0.98), 7-12 months (0.96; 95% CI, 0.91-1.01), and during the second year after delivery (0.95; 95% CI, 0.92-0.99). CONCLUSIONSThe rate of cancer during pregnancy was lower than expected for all sites, a finding that could not be explained entirely by delayed diagnosis. A rebound in the number of observed cases after delivery was restricted to melanoma, nervous system malignancies, and breast and thyroid cancer. Cancer 2015;121:2072-2077. (c) 2015 American Cancer Society. Fewer cancers than expected are found during pregnancy, a finding that cannot be explained entirely by delayed diagnosis.
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| 2. |
- Johansson, Anna L. V., et al.
(author)
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Mortality in women with pregnancy-associated malignant melanoma
- 2014
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In: The Journal of American Academy of Dermatology. - : Elsevier BV. - 0190-9622 .- 1097-6787. ; 71:6, s. 1093-1101
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Journal article (peer-reviewed)abstract
- Background: Malignant melanoma (MM) is one of the most common malignancies in young women. It remains debated whether a MM diagnosed during pregnancy or lactation has a worse prognosis. Objective: We sought to examine mortality in women with pregnancy-associated MM (PAMM) (diagnosed during pregnancy and up to 2-years postpartum). Methods: This was a population-based cohort study based on information retrieved from the Swedish Cancer and Multi-Generation Registers. Hazard ratios with 95% confidence intervals adjusted for age, period, education, parity, and tumor location were estimated. Results: In total, 6857 women and girls aged 15 to 44 years with a diagnosis of cutaneous MM between 1963 and 2009 were identified. Of these, 1019 cases were classified as PAMM. The cause-specific mortality did not differ between PAMM and MM not diagnosed near childbirth (adjusted hazard ratio 1.09, 95% confidence interval 0.83-1.42). Limitations: Information on stage at diagnosis was available only for a subset of patients Conclusion: Overall, the cause-specific mortality in women and girls with PAMM did not differ from that in women and girls with non-PAMM. The current findings do not provide evidence of an adverse prognostic influence of pregnancy or a recent birth.
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| 3. |
- Johansson, Anna L. V., et al.
(author)
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Stage at diagnosis and mortality in women with pregnancy-associated breast cancer (PABC)
- 2013
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 139:1, s. 183-192
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Journal article (peer-reviewed)abstract
- Converging evidence indicates that women with pregnancy-associated breast cancer (PABC) have increased mortality compared to women with breast cancer not diagnosed near pregnancy (non-PABC). Our aim was to investigate if the stage distribution differs between PABC and non-PABC and if stage at diagnosis can explain the poorer prognosis observed among women with PABC. We identified 3,282 breast cancers in women aged 15-44 years at diagnosis for whom staging data (tumor size, nodal involvement, metastasis) were available in the Swedish Cancer Register between 2002 and 2009. Information on reproductive history and vital status was obtained from the Multi-Generation Register and the Cause of Death Register. PABC was defined as breast cancers diagnosed during pregnancy and up to 2 years after delivery (n = 317). Non-PABC was defined as cases diagnosed before pregnancy or more than 2 years postpartum. Stage distributions were compared between PABC and non-PABC, and mortality rates were modeled using Cox regression. Compared to women with non-PABC, the mortality was almost 50 % higher in women with PABC [unadjusted hazard ratio (HR) 1.47 (95 % CI 1.04-2.08)], a difference which was reduced after adjustment for age and calendar year of diagnosis [HR 1.27 (95 % CI 0.88-1.83)]. Although advanced stage of breast cancer at diagnosis was more common among PABC than among non-PABC, further adjustment for stage only slightly reduced the HR [1.22 (95 % CI 0.84-1.78)]. The difference in mortality between PABC and non-PABC was more pronounced among women above 35 years and among women with PABC diagnosed within 1 year postpartum. Age, rather than stage at diagnosis, appears to act as the principal driver of the increased mortality observed in women with PABC. However, these findings do not preclude an untoward influence on mortality by pregnancy-associated factors affecting tumor aggressiveness and progression.
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| 4. |
- Johansson, Anna L.V., et al.
(author)
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Tumor characteristics and prognosis in women with pregnancy-associated breast cancer
- 2018
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:7, s. 1343-1354
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Journal article (peer-reviewed)abstract
- There is evidence of poor prognosis in women with pregnancy-associated breast cancer (PABC) diagnosed during pregnancy or within 2 years of delivery. Using a large, population-based cohort, we examined clinicopathologic features and survival in women with PABC. A cohort of women diagnosed with invasive breast cancer between 1992 and 2009 at ages 15-44 years was identified in the Swedish Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for each woman were retrieved from the Swedish Multi-Generation Register. Age-standardized distributions of tumor stage (tumor size, nodal status, metastasis), Elston grade and ER/PR/HER2 status were compared between nulliparous women and women with breast cancer during pregnancy and up to 10 years postdelivery. Adjusted hazard ratios for all-cause mortality rates among patients were estimated using Cox regression. We identified 1,661 nulliparous women with breast cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within second year postdelivery) and 3,598 during 2-10 years postdelivery. Compared to nulliparous women, women with PABC, and especially women diagnosed 0-12 months after delivery, had more advanced T and N stage, and higher proportions of ER/PR negative, HER2 positive and triple-negative tumors. Increased hazard ratios were observed in women diagnosed within 5 years of delivery after adjustment for age, year, education and region. Following additional adjustment for tumor characteristics, the hazard ratios were attenuated and nonsignificant. The poorer prognosis observed in women with PABC appears to be largely explained by more adverse tumor characteristics at diagnosis.
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| 5. |
- Landtblom, Anna Ravn, et al.
(author)
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Childbirth rates in women with myeloproliferative neoplasms
- 2024
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In: Leukemia. - : SPRINGERNATURE. - 0887-6924 .- 1476-5551.
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Journal article (peer-reviewed)abstract
- Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15-44 years with an MPN diagnosis 1973-2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68-0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86-1.22) while the HR was 0.50 (0.33-0.76) in PV and 0.45 (0.28-0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.
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| 6. |
- Landtblom, Anna Ravn, et al.
(author)
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Pregnancy and childbirth outcomes in women with myeloproliferative neoplasms-a nationwide population-based study of 342 pregnancies in Sweden
- 2022
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In: Leukemia. - : SPRINGER NATURE. - 0887-6924 .- 1476-5551. ; 36:10, s. 2461-2467
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Journal article (peer-reviewed)abstract
- Pregnancy and childbirth in women with myeloproliferative neoplasms (MPN) are reported to be associated with maternal thrombosis, hemorrhage, and placental dysfunction. To assess the risks of adverse events in pregnancy in women with MPN, we performed a large population-based study using Swedish health care registers, and included all pregnancies that had reached gestational week 22 (prior to 2008, week 28) during the years 1973-2017 in women with MPN. Control pregnancies were matched 1:1 for age, calendar year, and parity. We identified 342 pregnancies in 229 women with MPN. Preterm birth was significantly increased in pregnancies in MPN, 14% compared to 4% of pregnancies in controls (p < 0.001). Correspondingly, low birth weight (<2500 g) was also significantly increased in MPN pregnancies (p = 0.042). Stillbirth was rare, with two events (0.6%) in MPN, none in controls. Maternal thrombotic complications occurred in three (1%) of the pregnancies in MPN patients, compared to none in controls. Pregnancy-related bleeding affected 14% of pregnancies in MPN and 9% in controls (p < 0.110). Cesarean section was significantly more common in pregnancies in MPN. Incidence was 12.2 per 100.000 pregnancies. In summary, preterm birth was an important complication in MPN pregnancies, while maternal complications were less common than previously reported.
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| 7. |
- Lu, Donghao, et al.
(author)
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Clinical Diagnosis of Mental Disorders Immediately Before and After Cancer Diagnosis : A Nationwide Matched Cohort Study in Sweden
- 2016
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In: JAMA oncology. - Chicago, USA : American Medical Association. - 2374-2445 .- 2374-2437. ; 2:9, s. 1188-1196
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Journal article (peer-reviewed)abstract
- Importance: Psychiatric comorbidities are common among patients with cancer. However, whether or not there is increased risk of mental disorders during the diagnostic workup leading to a cancer diagnosis was unknown.Objective: To examine the relative risks of depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder during the periods before and after cancer diagnosis compared with individuals without cancer.Design, Setting, and Participants: Nationwide matched cohort study from January 1, 2001, to December 31, 2010, in a Swedish population and health registers.Main Outcomes and Measures: We estimated the time-varying hazard ratios (HRs) of the first clinical diagnosis of the studied mental disorders from 2 years before cancer diagnosis, through the time of diagnosis, and until 10 years after diagnosis, adjusting for age, sex, calendar period, and educational level. To assess milder mental conditions and symptoms, we further assessed the use of related psychiatric medications for patients with cancer diagnosed during 2008-2009.Results: The study included 304 118 patients with cancer and 3 041 174 cancer-free individuals who were randomly selected from the Swedish population and individually matched to the patients with cancer on year of birth and sex. The median age at diagnosis for the patients with cancer was 69 years, and 46.9% of the patients were female. The relative rate for all studied mental disorders started to increase from 10 months before cancer diagnosis (HR, 1.1; 95% CI, 1.1-1.2), peaked during the first week after diagnosis (HR, 6.7; 95% CI, 6.1-7.4), and decreased rapidly thereafter but remained elevated 10 years after diagnosis (HR, 1.1; 95% CI, 1.1-1.2). The rate elevation was clear for all main cancers except nonmelanoma skin cancer and was stronger for cancers of poorer prognosis. Compared with cancer-free individuals, increased use of psychiatric medications was noted from 1 month before cancer diagnosis and peaked around 3 months after diagnosis among patients with cancer.Conclusions and Relevance: Patients diagnosed as having cancer had increased risks of several common mental disorders from the year before diagnosis. These findings support the existing guidelines of integrating psychological management into cancer care and further call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.
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| 8. |
- Lu, Donghao, et al.
(author)
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Increased risk for psychiatric disorders immediately before and after cancer diagnosis : A nationwide matched cohort study in Sweden
- 2015
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 61, s. 50-50
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Journal article (other academic/artistic)abstract
- Purpose: To examine whether undergoing diagnostic workup leading up to a cancer diagnosis entrails increased risks for depression, anxiety disorder, substance use disorder, somatoform/conversion disorder, severe stress and adjustment disorder.Methods: Based on the nationwide health registers in Sweden, we conducted a matched cohort study during 2001–2010, including 304,118 cancer patients and five cancer-free individuals per cancer patient randomly selected from the Swedish population and matched on year of birth and sex. Flexible parametric survival models were used to estimate the time-varying hazard ratios [HRs] of any first in-/outpatient diagnosis of the studied psychiatric disorders from two years before cancer diagnosis (Year−2), through the time at diagnosis (Year 0), until ten years after diagnosis (Year 10).Results: The overall risk for the studied psychiatric disorders started to increase from Year−1 (HR 1.2, 95% confidence interval [CI] 1.0–1.5), peaked immediately after diagnosis (Week 1: HR 12.9, 95% CI 9.4–17.8), and decreased rapidly thereafter to be comparable with cancer-free individuals at approximately Year 10 (HR 1.0, 95% CI 0.8–1.3). The risk elevation was clear for all main cancer types except for non-melanoma skin cancer; and was stronger for cancers of relatively poor prognosis after (P= 0.0005) but not before diagnosis (P= 0.47).Conclusion: Patients recently diagnosed with cancer experience a dramatic increase in risks of psychiatric disorders. The clear risk elevation during the year before diagnosis suggests an impact of cancer symptoms pre-diagnosis as well as the stress of undergoing clinical evaluation for a suspected malignancy. This work is supported by Cancerfonden and FORTE.
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| 9. |
- Andersson, Mattias K, 1979, et al.
(author)
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ATR is a MYB regulated gene and potential therapeutic target in adenoid cystic carcinoma
- 2020
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In: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 9
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Journal article (peer-reviewed)abstract
- Adenoid cystic carcinoma (ACC) is a rare cancer that preferentially occurs in the head and neck, breast, as well as in other sites. It is an aggressive cancer with high rates of recurrence and distant metastasis. Patients with advanced disease are generally incurable due to the lack of effective systemic therapies. Activation of the master transcriptional regulator MYB is the genomic hallmark of ACC. MYB activation occurs through chromosomal translocation, copy number gain or enhancer hijacking, and is the key driving event in the pathogenesis of ACC. However, the functional consequences of alternative mechanisms of MYB activation are still uncertain. Here, we show that overexpression of MYB or MYB-NFIB fusions leads to transformation of human glandular epithelial cells in vitro and results in analogous cellular and molecular consequences. MYB and MYB-NFIB expression led to increased cell proliferation and upregulation of genes involved in cell cycle control, DNA replication, and DNA repair. Notably, we identified the DNA-damage sensor kinase ATR, as a MYB downstream therapeutic target that is overexpressed in primary ACCs and ACC patient-derived xenografts (PDXs). Treatment with the clinical ATR kinase inhibitor VX-970 induced apoptosis in MYB-positive ACC cells and growth inhibition in ACC PDXs. To our knowledge, ATR is the first example of an actionable target downstream of MYB that could be further exploited for therapeutic opportunities in ACC patients. Our findings may also have implications for other types of neoplasms with activation of the MYB oncogene.
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| 10. |
- Andersson, Therese M. -L., et al.
(author)
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Estimating the cure proportion of malignant melanoma, an alternative approach to assess long term survival : A population-based study
- 2014
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In: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 38:1, s. 93-99
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Journal article (peer-reviewed)abstract
- Objectives: A large proportion of patients with cutaneous malignant melanoma (CMM) do not experience excess mortality due to their disease. This group of patients is referred to as the cure proportion. Few studies have examined the possibility of cure for CMM. The aim of this study was to estimate the cure proportion of patients with CMM in a Swedish population. Methods: We undertook a population-based study of 5850 CMM patients in two Swedish health care regions during 1996-2005. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by stage, sex, age and anatomical site. Results: Disease stage at diagnosis was the most important factor for the probability of cure, with a cure proportion of approximately 1.0 for stage IA. While the probability of cure decreased with older age, the influence of age was smaller on the MST of uncured. Differences in prognosis between males and females were mainly attributed to differences in cure as opposed to differences in MST of uncured. Conclusions: This population-based study showed approximately 100% cure among stage IA disease. Almost 50% of patients had stage IA disease and the high cure proportion for this large patient group is reassuring.
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| 11. |
- Andersson, Therese M L
(author)
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Quantifying cancer patient survival : extensions and applications of cure models and life expectancy estimation
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Cancer patient survival is the single most important measure of cancer patient care. By quantifying cancer patient survival in different ways further insights can be gained in terms of temporal trends and differences in cancer patient survival between groups. The objective of this thesis is to develop and apply methods for estimating the cure proportion and loss in expectation of life for cancer patients. In paper I, a cure model was used to study temporal trends in survival of patients with acute myeloid leukaemia in Sweden. Cancer patient survival was estimated in a relative survival setting and quantified as the proportion cured and the median survival time of uncured for different age groups and by calendar time of diagnosis. We found a dramatic increase in the cure proportion for the age group 19-40, although almost no improvement was seen for patients aged 70-79 at diagnosis. In paper II, a flexible parametric cure model was developed to overcome some limitations with standard parametric cure models. This model is a special case of a non-mixture cure model, using splines instead of a parametric distribution for the modeling. The fit of the flexible parametric cure model was compared to the fit of a Weibull non-mixture cure model, and shown to be superior in cases when the standard non-mixture cure model did not give a good fit or did not converge. Software was developed to enable use of the method. In paper III, the possibility of using a flexible parametric relative survival model for estimating life expectancy and loss in expectation of life was evaluated. Extrapolation of the survival function is generally needed, and the flexible parametric relative survival model was shown to extrapolate the survival very well. The method was evaluated by comparing survival functions extrapolated from 10 years past diagnosis to observed survival by the use of data with 40 years of follow-up. Software was developed to enable use of the method. In paper IV, the life expectancy and loss in expectation of life was estimated for colon cancer patients in Sweden. Even though relative survival was similar across age for colon cancer patients, the loss in expectation of life varied greatly by age, since young patients have more years to lose. We also found that the life expectancy of colon cancer patients improved over time. However, the improvement has to a large extent mimicked the improvement seen in the general population, and therefore there were no large changes in the loss in expectation of life. In conclusion, the methods presented in this thesis are additional tools for estimating and quantifying population-based cancer patient survival, that can lead to an improved understanding of different aspects of the prognosis of cancer patients.
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| 12. |
- Andersson, Therese M-L, et al.
(author)
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The loss in expectation of life after colon cancer : a population-based study
- 2015
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 15
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Journal article (peer-reviewed)abstract
- Background: To demonstrate how assessment of life expectancy and loss in expectation of life can be used to address a wide range of research questions of public health interest pertaining to the prognosis of cancer patients. Methods: We identified 135,092 cases of colon adenocarcinoma diagnosed during 1961-2011 from the population-based Swedish Cancer Register. Flexible parametric survival models for relative survival were used to estimate the life expectancy and the loss in expectation of life. Results: The loss in expectation of life for males aged 55 at diagnosis was 13.5 years (95 % CI 13.2-13.8) in 1965 and 12.8 (12.4-13.3) in 2005. For males aged 85 the corresponding figures were 3.21 (3.15-3.28) and 2.10 (2.04-2.17). The pattern was similar for females, but slightly greater loss in expectation of life. The loss in expectation of life is reduced given survival up to a certain time point post diagnosis. Among patients diagnosed in 2011, 945 life years could potentially be saved if the colon cancer survival among males could be brought to the same level as for females. Conclusion: Assessment of loss in expectation of life facilitates the understanding of the impact of cancer, both on individual and population level. Clear improvements in survival among colon cancer patients have led to a gain in life expectancy, partly due to a general increase in survival from all causes.
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| 13. |
- Andrae, Bengt, et al.
(author)
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Screening and cervical cancer cure: population based cohort study.
- 2012
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In: BMJ (Clinical research ed.). - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 344
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Journal article (peer-reviewed)abstract
- To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death.
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| 14. |
- Biccler, Jorne Lionel, et al.
(author)
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Relapse Risk and Loss of Lifetime After Modern Combined Modality Treatment of Young Patients With Hodgkin Lymphoma : A Nordic Lymphoma Epidemiology Group Study
- 2019
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In: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 37:9, s. 703-713
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Journal article (peer-reviewed)abstract
- PURPOSE: Estimates of short- and long-term survival for young patients with classic Hodgkin lymphoma (cHL) are of considerable interest. We investigated cHL prognosis in the era of contemporary treatment at different milestones during the follow-up.PATIENTS AND METHODS: On the basis of a Nordic cohort of 2,582 patients diagnosed at ages 18 to 49 years between 2000 and 2013, 5-year relapse risks and 5-year restricted losses in expectation of lifetime were estimated for all patients and for patients who achieved event-free survival (EFS) for 12 (EFS12), 24 (EFS24), 36 (EFS36) or 60 (EFS60) months. The median follow-up time was 9 years (range, 2.9 to 16.8 years).RESULTS: The 5-year overall survival was 95% (95% CI, 94% to 96%). The 5-year risk of relapse was 13.4% (95% CI, 12.1% to 14.8%) overall but decreased to 4.2% (95% CI, 3.8% to 4.6%) given that patients reached EFS24. Relapse risk for patients treated with six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) was comparable to that of patients treated with six to eight courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) despite more adverse risk criteria among patients treated with BEACOPP. Both from diagnosis and if EFS24 was reached, the losses in expectation of lifetime during the following 5 years were small (from diagnosis, 45 days [95% CI, 35 to 54 days] and for patients who reached EFS24, 13 days [95% CI, 7 to 20 days]). In stage-stratified analyses of 5-year restricted loss in expectation of lifetime, patients with stages I to IIA disease had no noteworthy excess risk of death after they reached EFS24, whereas risk remained measurable for patients with stages IIB to IV cHL.CONCLUSION: Real-world data on young patients with cHL from the Nordic countries show excellent outcomes. The outlook is particularly favorable for patients who reach EFS24, which supports limited relapse-oriented clinical follow-up.
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| 15. |
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| 16. |
- Bonagas, Nadilly, et al.
(author)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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In: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Journal article (peer-reviewed)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 17. |
- Bower, Hannah, et al.
(author)
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Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population
- 2016
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:24, s. 2851-2858
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Journal article (peer-reviewed)abstract
- PURPOSE: A dramatic improvement in the survival of patients with chronic myeloid leukemia (CML) occurred after the introduction of imatinib mesylate, the first tyrosine kinase inhibitor (TKI). We assessed how these changes affected the life expectancy of patients with CML and life-years lost as a result of CML between 1973 and 2013 in Sweden.MATERIALS AND METHODS: Patients recorded as having CML in the Swedish Cancer Registry from 1973 to 2013 were included in the study and followed until death, censorship, or end of follow-up. The life expectancy and loss in expectation of life were predicted from a flexible parametric relative survival model.RESULTS: A total of 2,662 patients with CML were diagnosed between 1973 and 2013. Vast improvements in the life expectancy of these patients were seen over the study period; larger improvements were seen in the youngest ages. The great improvements in life expectancy translated into great reductions in the loss in expectation of life. Patients of all ages diagnosed in 2013 will, on average, lose < 3 life-years as a result of CML.CONCLUSION: Imatinib mesylate and new TKIs along with allogeneic stem cell transplantation and other factors have contributed to the life expectancy in patients with CML approaching that of the general population today. This will be an important message to convey to patients to understand the impact of a CML diagnosis on their life. In addition, the increasing prevalence of patients with CML will have a great effect on future health care costs as long as continuous TKI treatment is required.
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| 18. |
- Bower, Hannah, et al.
(author)
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Reply to D. Pulte et al.
- 2017
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 35:6, s. 696-697
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Journal article (peer-reviewed)
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| 19. |
- Eloranta, Sandra, et al.
(author)
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How can we make cancer survival statistics more useful for patients and clinicians : an illustration using localized prostate cancer in Sweden
- 2013
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 24:3, s. 505-515
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Journal article (peer-reviewed)abstract
- Studies of cancer patient survival typically report relative survival or cause-specific survival using data from patients diagnosed many years in the past. From a risk-communication perspective, such measures are suboptimal for several reasons; their interpretation is not transparent for non-specialists, competing causes of death are ignored and the estimates are unsuitable to predict the outcome of newly diagnosed patients. In this paper, we discuss the relative merits of recently developed alternatives to traditionally reported measures of cancer patient survival. In a relative survival framework, using a period approach, we estimated probabilities of death in the presence of competing risks. To illustrate the methods, we present estimates of survival among 23,353 initially untreated, or hormonally treated men with intermediate- or high-risk localized prostate cancer using Swedish population-based data. Among all groups of newly diagnosed patients, the probability of dying from prostate cancer, accounting for competing risks, was lower compared to the corresponding estimates where competing risks were ignored. Accounting for competing deaths was particularly important for patients aged more than 70 years at diagnosis in order to avoid overestimating the risk of dying from prostate cancer. We argue that period estimates of survival, accounting for competing risks, provide the tools to communicate the actual risk that cancer patients, diagnosed today, face to die from their disease. Such measures should offer a more useful basis for risk communication between patients and clinicians and we advocate their use as means to answer prognostic questions.
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| 20. |
- Eriksson, Hanna, et al.
(author)
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The proportion cured of patients diagnosed with Stage III-IV cutaneous malignant melanoma in Sweden 1990-2007 : A population-based study.
- 2016
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 138:12
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Journal article (peer-reviewed)abstract
- The survival in cutaneous malignant melanoma (CMM) is highly dependent on the stage of the disease. Stage III-IV CMM patients are at high risk of relapse with a heterogeneous outcome, but not all experience excess mortality due to their disease. This group is referred to as the cure proportion representing the proportion of patients who experience the same mortality rate as the general population. The aim of this study was to estimate the cure proportion of patients diagnosed with Stage III-IV CMM in Sweden. From the population-based Swedish Melanoma Register, we included 856 patients diagnosed with primary Stage III-IV CMM, 1990-2007, followed-up through 2013. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by sex, age, tumor site, ulceration status (in Stage III patients) and disease stage. The standardized (over sex, age and site) cure proportion was lower in Stage IV CMMs (0.15, 95% CI 0.09-0.22) than non-ulcerated Stage III CMMs (0.48, 95% CI 0.41-0.55) with a statistically significant difference of 0.33 (95% CI = 0.24-0.41). Ulcerated Stage III CMMs had a cure proportion of 0.27 (95% CI 0.21-0.32) with a statistically significant difference compared to non-ulcerated Stage III CMMs (difference 0.21; 95% CI = 0.13-0.30). The standardized MST of uncured was approximately 9-10 months longer for non-ulcerated versus ulcerated Stage III CMMs. We could demonstrate a significantly better outcome in patients diagnosed with non-ulcerated Stage III CMMs compared to ulcerated Stage III CMMs and Stage IV disease after adjusting for age, sex and tumor site.
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| 21. |
- Hedelin, Maria, 1964, et al.
(author)
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Dietary Phytoestrogens and the Risk of Ovarian Cancer in the Womens Lifestyle and Health Cohort Study
- 2011
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In: CANCER EPIDEMIOLOGY BIOMARKERS and PREVENTION. - : American Association for Cancer Research Inc. - 1055-9965. ; 20:2, s. 308-317:20, s. 308-317
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Journal article (peer-reviewed)abstract
- Background: Dietary intake of phytoestrogens has been inversely associated to hormone-dependent cancers, such as prostate and breast cancers. Few studies have investigated the association between ovarian cancer and intake of phytoestrogens. We evaluated the associations between intake of phytoestrogens (isoflavonoids/lignans/coumestrol) and fiber (vegetable/cereal) and risk of ovarian cancer. Methods: In 1991-1992 a prospective population-based cohort study among Swedish women was conducted, including 47,140 women with complete dietary questionnaire data. During follow-up until December 2007, 163 women developed invasive (n = 117) and borderline (n = 46) ovarian cancers. The median follow-up time was 16 years and total person year was 747,178. Cox proportional hazards models were conducted to estimate multivariate risk ratios, 95% CI for associations with risk of ovarian cancer. Results: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. In addition, we found no statistically significant association between intake of specific food items rich in phytoestrogens (berries, nuts, beans/soy, and crisp or whole-grain bread) and ovarian cancer risk overall. Fiber and coumestrol was inversely associated with borderline ovarian cancer, but not with invasive ovarian cancer. Conclusions: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. Impact: Phytoestrogens do not play a major etiologic role in ovarian cancer, at least among women in this Swedish cohort with low bean/soy intake. However, our results of a difference in the effect of fiber or coumestrol between invasive and borderline ovarian cancer need to be evaluated in larger studies.
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| 22. |
- Krakowski, Isabelle, et al.
(author)
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Association of metformin use and survival in patients with cutaneous melanoma and diabetes
- 2023
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In: The British journal of dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 188:1, s. 32-40
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Journal article (peer-reviewed)abstract
- BACKGROUND: Metformin use has been associated with improved survival in patients with different types of cancer, but research regarding the effect of metformin on cutaneous melanoma (CM) survival is sparse and inconclusive.OBJECTIVES: To investigate the association between metformin use and survival among patients with CM and diabetes.METHODS: All adult patients with a primary invasive CM between 2007 and 2014 were identified in the Swedish Melanoma Registry and followed until death, or end of follow-up on 31 December 2017 in this population-based cohort study. Patients with both CM and type 2 diabetes mellitus were assessed further. Overall survival (OS) and melanoma-specific survival (MSS) were the primary endpoints. Cox proportional hazard models estimating crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used comparing peridiagnostic use vs. nonuse of metformin. Dose response was evaluated based on defined daily doses.RESULTS: Among a total of 23 507 patients, 1162 patients with CM and type 2 diabetes mellitus were included in the final cohort, with a median follow-up time of 4.1 years (interquartile range 2.4-6.1). Peridiagnostic metformin use was associated with a significantly decreased risk of death by any cause (HR 0.68, 95% CI 0.57-0.81). Cumulative pre- and postdiagnostic metformin use was also associated with improved OS: the HR for prediagnostic use was 0.90 (95% CI 0.86-0.95) for every 6 months of use and the HR for postdiagnostic use ranged from 0.98 (95% CI 0.97-0.98) for 0-6 months to 0.59 (0.49-0.70) for 24-30 months of use. No association was found for metformin use and MSS.CONCLUSIONS: Metformin use was associated with improved OS in patients with CM and diabetes regardless of timing (pre-, post- or peridiagnostic use) and followed a dose-response pattern. However, further research regarding the underlying mechanisms is warranted.
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| 23. |
- Kristinsson, Sigurdur Y, et al.
(author)
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Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.
- 2009
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In: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 94:12, s. 1714-1720
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Journal article (peer-reviewed)abstract
- BACKGROUND: There are limited data on survival patterns among patients with monoclonal gammopathy of undetermined significance. DESIGN AND METHODS: We compared the survival of 4,259 patients with monoclonal gammopathy of undetermined significance, collected from hematology outpatient units in Sweden, with the survival of the general population by computing relative survival ratios. We also compared causes of death in these patients with those in 16,151 matched controls. RESULTS: One-, 5-, 10-, and 15-year relative survival ratios were 0.98 (95% CI 0.97-0.99), 0.93 (0.91-0.95), 0.82 (0.79-0.84), and 0.70 (0.64-0.76), respectively. Younger age at diagnosis of the gammopathy was associated with a significantly lower excess mortality compared to that in older patients (p<0.001). The excess mortality among patients with gammopathy increased with longer follow-up (p<0.0001). IgM (versus IgG/A) gammopathy was associated with a superior survival (p=0.038). Patients with monoclonal gammopathy of undetermined significance had an increased risk of dying from multiple myeloma (hazards ratio (HR)=553; 95% CI 77-3946), Waldenström's macroglobulinemia (HR=infinity), other lymphoproliferative malignancies (6.5; 2.8-15.1), other hematologic malignancies (22.9; 8.9-58.7), amyloidosis (HR=infinity), bacterial infections (3.4; 1.7-6.7), ischemic heart disease (1.3; 1.1-1.4), other heart disorders (1.5; 1.2-1.8), other hematologic conditions (6.9; 2.7-18), liver (2.1; 1.1-4.2), and renal diseases (3.2; 2.0-4.9). CONCLUSIONS: Our finding of decreased life expectancy in patients with monoclonal gammopathy of undetermined significance, which was most pronounced in the elderly and explained by both malignant transformation and non-malignant causes, is of importance in the understanding and clinical management of this disease. The underlying mechanisms may be causally related to the gammopathy, but may also be explained by underlying disease that led to the detection of the hematologic disease. Our results are of importance since they give a true estimation of survival in patients with monoclonal gammopathy of undetermined significance diagnosed in clinical practice.
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| 24. |
- Kristinsson, Sigurdur Y., et al.
(author)
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Patterns of survival in lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia: A population-based study of 1,555 patients diagnosed in Sweden from 1980 to 2005
- 2013
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In: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 88:1, s. 60-65
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Journal article (peer-reviewed)abstract
- Clinical management of lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) has changed considerably over recent years, reflected in the use of new therapeutic agents (purine analogs, monoclonal antibodies, thalidomide- and bortezomib-based therapies). No population-based studies and few randomized trials have been performed to assess survival in newly diagnosed LPL/WM. We performed a large population-based study in Sweden including 1,555 LPL/WM patients diagnosed from 1980 to 2005. Relative survival ratios (RSRs) and excess mortality rate ratios (EMRR) were computed as measures of survival. Survival of LPL/WM patients has improved significantly (P = 0.007) over time with 5-year RSR = 0.57 (95% confidence interval [CI] 0.460.68), 0.65 (0.570.73), 0.74 (0.680.80), 0.72 (0.660.77), and 0.78 (0.710.85) for patients diagnosed during the calendar periods 19801985, 19861990, 19911995, 19962000, and 20012005, respectively. Improvement in 1- and 5-year relative survival was found in all age groups and for LPL and WM separately. Patients with WM had lower excess mortality compared to LPL (EMRR = 0.38; 95% CI 0.300.48). Older age at diagnosis was associated with a poorer survival (P < 0.001). Taken together, we found a significant improvement in survival in LPL/WM over time. Despite this progress, new effective agents with a more favourable toxicity profile are needed to further improve survival in LPL/WM, especially in the elderly. Am. J. Hematol. 2013. (c) 2012 Wiley Periodicals, Inc.
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| 25. |
- Landtblom, Anna Ravn, et al.
(author)
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Risk of infections in patients with myeloproliferative neoplasms-a population-based cohort study of 8363 patients
- 2021
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In: Leukemia. - : NATURE PUBLISHING GROUP. - 0887-6924 .- 1476-5551. ; 35, s. 476-484
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Journal article (peer-reviewed)abstract
- Infections are a common complication in patients with many hematologic malignancies, however, whether patients with myeloproliferative neoplasms (MPN) also are at an increased risk of infections is largely unknown. To assess the risk of serious infections, we performed a large population-based matched cohort study in Sweden including 8 363 MPN patients and 32,405 controls using high-quality registers between the years 1992-2013 with follow-up until 2015. The hazard ratio (HR) of any infection was 2.0 (95% confidence interval 1.9-2.0), of bacterial infections 1.9 (1.8-2.0), and of viral infections 2.1 (1.9-2.3). One of the largest risk increases was that of sepsis, HR 2.6 (2.4-2.9). The HR of any infection was highest in primary myelofibrosis 3.7 (3.2-4.1), and significantly elevated in all MPN subtypes; 1.7 (1.6-1.8) in polycythemia vera and 1.7 (1.5-1.8) in essential thrombocythemia. There was no significant difference in risk of infections between untreated patients and patients treated with hydroxyurea or interferon-alpha during the years 2006-2013. These novel findings of an overall increased risk of infections in MPN patients, irrespective of common cytoreductive treatments, suggest the increased risk of infection is inherent to the MPN.
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| 26. |
- Moller, Elisabeth, et al.
(author)
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The Nordic Nutrition Recommendations and prostate cancer risk in the Cancer of the Prostate in Sweden (CAPS) study
- 2012
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In: Public Health Nutrition. - : CAMBRIDGE UNIV PRESS. - 1368-9800 .- 1475-2727. ; 15:10, s. 1897-1908
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Journal article (peer-reviewed)abstract
- Objective: The Nordic Nutrition Recommendations (NNR) aim at preventing diet-associated diseases such as cancer in the Nordic countries. We evaluated adherence to the NNR in relation to prostate cancer (PC) in Swedish men, including potential interaction with a genetic risk score and with lifestyle factors. Design: Population-based case-control study (Cancer of the Prostate in Sweden (CAPS), 2001-2002). Using data from a semi-quantitative FFQ, we created an NNR adherence score and estimated relative risks of PC by unconditional logistic regression. Individual score components were modelled separately and potential modifying effects were assessed on the multiplicative scale. Setting: Four regions in the central and northern parts of Sweden. Subjects: Incident PC patients (n 1386) and population controls (n 940), frequency-matched on age and region. Results: No overall association with PC was found, possibly due to the generally high adherence to the NNR score and its narrow distribution in the study population. Among individual NNR score components, high compared with low intakes of polyunsaturated fat were associated with an increased relative risk of localized PC. No formal interaction with genetic or lifestyle factors was observed, although in stratified analysis a positive association between the NNR and PC was suggested among men with a high genetic risk score but not among men with a medium or low genetic risk score. Conclusions: Our findings do not support an association between NNR adherence and PC. The suggestive interaction with the genetic risk score deserves further investigations in other study populations.
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| 27. |
- Möller, Elisabeth, et al.
(author)
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Mediterranean Diet Score and prostate cancer risk in a Swedish population-based case-control study
- 2013
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In: Journal of Nutritional Science. - : Cambridge University Press (CUP). - 2048-6790. ; 2
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Journal article (peer-reviewed)abstract
- Several individual components of the Mediterranean diet have been shown to offer protection against prostate cancer. The present study is the first to investigate the association between adherence to the Mediterranean diet and the relative risk of prostate cancer. We also explored the usefulness of the Mediterranean Diet Score (MDS) in a non-Mediterranean population. FFQ data were obtained from 1482 incident prostate cancer patients and 1108 population-based controls in the Cancer of the Prostate in Sweden (CAPS) study. We defined five MDS variants with different components or using either study-specific intakes or intakes in a Greek reference population as cut-off values between low and high intake of each component. Unconditional logistic regression was used to estimate the relative risk of prostate cancer for high and medium v. low MDS, as well as potential associations with the individual score components. No statistically significant association was found between adherence to the Mediterranean diet based on any of the MDS variants and prostate cancer risk (OR range: 0·96-1·19 for total prostate cancer, comparing high with low adherence). Overall, we found little support for an association between the Mediterranean diet and prostate cancer in this Northern European study population. Despite potential limitations inherent in the study or in the build-up of a dietary score, we suggest that the original MDS with study-specific median intakes as cut-off values between low and high intake is useful in assessing the adherence to the Mediterranean diet in non-Mediterranean populations.
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| 28. |
- Norda, Rut, et al.
(author)
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The impact of plasma preparations and their storage time on short-term posttransfusion mortality : A population-based study using the Scandinavian Donation and Transfusion database
- 2012
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In: Journal of Trauma and Acute Care Surgery. - 2163-0755 .- 2163-0763. ; 72:4, s. 954-961
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Journal article (peer-reviewed)abstract
- BACKGROUND: The treatment of coagulopathy and bleeding in severe trauma requires rapid delivery of large amounts of plasma to emergency wards. The resulting need for adequate supplies of nonfrozen or thawed plasma has consequences for storage strategies. Using extensive population data from a setting where both fresh-frozen plasma (FFP) and cold-stored liquid plasma were used, this study investigates whether there is an association between short-term mortality after receipt of FFP or liquid plasma of different storage times. METHODS: A cohort of 84,986 Swedish patients was followed up from first recorded allogenic plasma transfusion for 14-day mortality. Associations with exposure to FFP were expressed as relative risks adjusted for patient characteristics, total transfusions, hospital, and calendar year. For non-FFP, the units given to patients who died and matched patients who survived were compared for their duration of storage. RESULTS: The relative risk of exposure to FFP was 1.19 (95% confidence interval: 1.12-1.27, p < 0.0001), with the risk elevation confined to the earlier calendar years of the study. There was no evidence of any effect of storage time of non-FFP. In analyses of all plasma types, FFP from male donors had lowest risk. CONCLUSIONS: Compared with exclusive use of never-frozen plasma, FFP was associated with increased short-term mortality in the era before leukocyte depletion. FFP from female donors had a significantly higher risk than male FFP. For non-FFP, duration of storage was unrelated to mortality. These findings can help to inform policies for managing high plasma demand in critical care.
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| 29. |
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| 30. |
- Reutfors, Johan, et al.
(author)
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Mortality in treatment-resistant unipolar depression : A register-based cohort study in Sweden
- 2018
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In: Journal of Affective Disorders. - : ELSEVIER SCIENCE BV. - 0165-0327 .- 1573-2517. ; 238, s. 674-679
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Journal article (peer-reviewed)abstract
- Background: The impact of treatment resistant depression (TRD) on mortality is not established. Methods: Using Swedish national registers, 118,774 patients between 18-69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). Results: In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21-1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69-2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31-1.76), highest among patients 18-29 years old (EMRR 2.03; 1.31-1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63-2.43). Limitations: Severity of depression and adherence to treatment were not available in the data. Conclusions: Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.
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| 31. |
- Song, Huan, et al.
(author)
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Waiting time for cancer treatment and mental health among patients with newly diagnosed esophageal or gastric cancer : A nationwide cohort study
- 2017
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: Except for overall survival, whether or not waiting time for treatment could influences other domains of cancer patients' overall well-being is to a large extent unknown. Therefore, we performed this study to determine the effect of waiting time for cancer treatment on the mental health of patients with esophageal or gastric cancer. Methods: Based on the Swedish National Quality Register for Esophageal and Gastric Cancers (NREV), we followed 7,080 patients diagnosed 2006-2012 from the time of treatment decision. Waiting time for treatment was defined as the interval between diagnosis and treatment decision, and was classified into quartiles. Mental disorders were identified by either clinical diagnosis through hospital visit or prescription of psychiatric medications. For patients without any mental disorder before treatment, the association between waiting time and subsequent onset of mental disorders was assessed by hazard ratios (HRs) with 95% confidence interval (CI), derived from multivariable-adjusted Cox model. For patients with a preexisting mental disorder, we compared the rate of psychiatric care by different waiting times, allowing for repeated events. Results: Among 4,120 patients without any preexisting mental disorder, lower risk of new onset mental disorders was noted for patients with longer waiting times, i.e. 18-29 days (HR 0.86; 95% CI 0.74-1.00) and 30-60 days (HR 0.79; 95% CI 0.67-0.93) as compared with 9-17 days. Among 2,312 patients with preexisting mental disorders, longer waiting time was associated with more frequent psychiatric hospital care during the first year after treatment (37.5% higher rate per quartile increase in waiting time; p for trend = 0.0002). However, no such association was observed beyond one year nor for the prescription of psychiatric medications. Conclusions: These data suggest that waiting time to treatment for esophageal or gastric cancer may have different mental health consequences for patients depending on their past psychiatric vulnerabilities. Our study sheds further light on the complexity of waiting time management, and calls for a comprehensive strategy that takes into account different domains of patient well-being in addition to the overall survival.
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| 32. |
- Strand, Fredrik, et al.
(author)
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Longitudinal fluctuation in mammographic percent density differentiates between interval and screen-detected breast cancer
- 2016
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In: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Journal article (peer-reviewed)abstract
- Interval breast cancer (IC) has a more aggressive phenotype and higher mortality than screen-detected cancer (SDC). In this case-case study, we investigated whether the size of longitudinal fluctuations in mammographic percent density (PD fluctuation) was associated with the ratio of IC versus SDC among screened women with breast cancer. The primary study population consisted of 1,414 postmenopausal breast cancer cases, and the validation population of 1,241 cases. We calculated PD fluctuation as the quadratic mean of deviations between actual PD and the long-term trend estimated by a mixed effects model. In a logistic regression model we examined the association between PD fluctuation and IC versus SDC including adjustments for PD at last screening, age at diagnosis, BMI and hormone replacement therapy. All statistical tests were two-sided. There were 385 IC and 1,029 SDC in the primary study population, with PD fluctuations of 0.44 and 0.41 respectively (p = 0.0309). After adjustments, PD fluctuation was associated with an increased ratio of IC versus SDC, with an estimated per-standard deviation odds ratio of 1.17 (95% CI = 1.03-1.33), compared to 1.19 (95% CI = 1.04-1.38) in the validation population. In screened women with breast cancer, high fluctuation in mammographic percent density was associated with an increased ratio of IC versus SDC. Whether this is entirely related to a reduced mammographic detectability or to a biological phenotype promoting faster tumor growth remains to be elucidated.
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| 33. |
- Tynell, Elsa, et al.
(author)
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Should plasma from female donors be avoided? : A population-based cohort study of plasma recipients in Sweden from 1990 through 2002
- 2010
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In: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 50:6, s. 1249-1256
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Journal article (peer-reviewed)abstract
- BACKGROUND: Plasma from female donors has been implicated in the sometimes fatal complication known as transfusion-related acute lung injury. In studies of patients in intensive care units, worsened gas exchange of the lungs has also been attributed to female plasma. Despite a lack of population-based evidence, policies have already been introduced to exclude female donor plasma. STUDY DESIGN AND METHODS: Short-term mortality after plasma transfusion was investigated using data from the Scandinavian Donations and Transfusions (SCANDAT) database. A cohort of 92,565 patients in 30 Swedish hospitals were followed for 14 days after their first plasma transfusion. The relative risk (RR) of death in recipients of female plasma compared to recipients of only male plasma was estimated from Poisson regression. RESULTS: Recipients had median age 70 years, received a mean of 4.4 plasma units, and had an overall 14-day mortality of 8.43%. Sixty-eight percent were exposed to female plasma, with a 14-day mortality of 8.85% compared to 7.53% in the nonexposed group. After adjustment for potential confounding factors, the RRs were 1.16 (confidence interval [CI], 1.06-1.27) and 1.32 (CI, 1.17-1.49) for those receiving 3 to 4 and 5 or more units of female plasma, respectively. Risk estimates were increased in an analysis of deaths with a concomitant discharge diagnosis involving the respiratory or circulatory system or an adverse reaction. CONCLUSIONS: This large population-based cohort study of unselected patients suggests that transfusion of plasma from female donors confers a short-term survival disadvantage on recipients.
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| 34. |
- Weibull, Caroline E., et al.
(author)
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Temporal trends in treatment-related incidence of diseases of the circulatory system among Hodgkin lymphoma patients
- 2019
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In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:5, s. 1200-1208
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Journal article (peer-reviewed)abstract
- While Hodgkin lymphoma (HL) survival has improved, treatment-related complications remain a concern. As a measure of treatment-related diseases of the circulatory system (DCS) we report excess incidence of DCS and absolute risks among HL patients diagnosed in the modern treatment era. From the Swedish Cancer Register, we identified all HL patients diagnosed 1985 through 2013, at ages 18-80 years. Excess incidence rate ratios (EIRRs) with 95% confidence intervals (CIs) comparing excess DCS incidence between calendar periods were estimated overall, and at 5 and 10 years after diagnosis using flexible parametric models. Model-based predictions were used to obtain probabilities of being diagnosed with DCS, in the presence of competing risks. During follow-up, 726 (16%) of the 4,479 HL patients experienced DCS. Overall, the excess DCS incidence was lower during all calendar periods compared to the first (2009-2013 vs. 1985-1988: EIRR = 0.63, 95% CI: 0.42-0.95). The 5- and 10-year excess incidence of DCS decreased between 1985 and 1994 for 25-year-olds (5-year-EIRR1994 = 0.32, 95% CI: 0.12-0.92) and 60-year-olds (5-year-EIRR1994 = 0.45, 95% CI: 0.24-0.88), but remained stable thereafter. No improvements were observed among 75-year-olds. The probability of excess DCS remained the same throughout the study period. In 2009, the percentage of patients aged 25, 60 and 75 experiencing excess DCS within 5 years was 3.4, 15.0 and 17.0% (males) and 2.3, 10.8 and 12.6% (females). Treatment-related incidence of DCS has declined since the mid-1980s, but more recent improvements are absent and an excess risk remains. Continued efforts towards less toxic treatments are warranted, alongside primary prevention strategies.
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| 35. |
- Zoltek, Maximilian, et al.
(author)
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Health Anxiety and Its Relationship to Thyroid-Hormone-Suppression Therapy in Patients with Differentiated Thyroid Cancer
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:10
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Journal article (peer-reviewed)abstract
- Differentiated thyroid cancer (DTC) has a good prognosis; however, patients often need lifelong follow up, and they face potential side effects. The aim of this study was to investigate health anxiety among DTC patients and its relationship to TSH suppression. In 2020, patients from a previous cohort who were from Stockholm completed the 14-item Short Health Anxiety Inventory (SHAI-14; 0–42; 18 being the threshold for clinical significance) and a study-specific questionnaire. Clinical information was also retrieved from medical records. Linear regression was used to investigate the relationship between the TSH levels and the SHAI-14, while adjusting for potential confounders. In total, 146 (73%) patients were included. A total of 24 respondents (16%) scored 18 or more on the SHAI-14, and the mean score was 11.3. Patients with TSH levels of 0.1–0.5 (mE/L) scored, on average, 3.28 points more (p-value 0.01) on the SHAI-14 compared to patients with TSH levels > 0.5. There was no statistically significant difference between patients with TSH levels < 0.1 and TSH levels > 0.5. Thus, we found no linear relationship between the TSH values and health anxiety. Clinically significant levels of health anxiety are slightly higher than those in the general population, but do not appear to be a major psychiatric comorbidity among patients with DTC.
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