| 1. |
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| 2. |
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| 3. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 7. |
- Cordtz, R, et al.
(författare)
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RISK OF HAEMATOLOGICAL MALIGNANCY IN PATIENTS WITH PSORIATIC ARTHRITIS, OVERALL AND IN RELATION TO TNF INHIBITORS - A NORDIC COHORT STUDY
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 169-170
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Several autoimmune inflammatory diseases, including rheumatoid arthritis (RA), are associated with increased risk of malignant lymphomas. There is also a longstanding concern of lymphoma development with tumour necrosis factor inhibitor (TNFi) treatment, but most studies in RA to date do not indicate an additionally increased risk. Corresponding studies in psoriatic arthritis (PsA), both with respect to the underlying risks, and risks in relation to treatment with TNFi, are limited. Data on myeloid malignancies in PsA are scarce.ObjectivesTo estimate the risk of haematological malignancy overall and by lymphoid and myeloid types in TNFi treated versus (vs.) biologics-naïve patients with PsA across the five Nordic countries. Additionally, we investigated the underlying risk of haematological malignancies in PsA as compared to the general population.MethodsWe identified patients with PsA starting a first ever TNFi from the clinical rheumatology registers (CRR) in Sweden (SE), Denmark (DK), Norway (NO), Finland (FI), and Iceland (ICE) from 2006 through 2019 (n=10 621). We identified biologics-naïve patients with PsA from a) the CRR (n=18 705, all countries) and b) the national patient registers (NPR, n=27 286, SE and DK only). To estimate the underlying risk of haematological malignancy in PsA, we randomly sampled general population comparators in SE and DK matched on year of birth, sex, and calendar year at start of follow-up, to the patients with PsA.Through linkage to the mandatory national cancer registers in all five countries, we collected information on haematological malignancy overall, and categorised into lymphoid or myeloid types. By applying a modified Poisson regression, we estimated pooled incidence rate ratio (IRR) with 95% confidence intervals (CI) for TNFi treated vs. biologics-naïve PsA and for PsA vs. the general population, adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ResultsWe observed 40 events of haematological malignancies (during 59 827 person-years) among TNFi treated PsA, resulting in a crude incidence rate (IR) of 67 per 100 000 person-years. The corresponding IR was 91 (63 events) for biologics-naïve PsA from the CRR, and 118 (172 events) for biologics-naïve PsA from NPR. This resulted in a pooled IRR of 0.97 (0.69 to 1.37) for TNFi-treated vs. biologics-naïve PsA patients from the CRR, and 0.84 (0.64 to 1.10) vs. biologics-naïve PsA patients from the NPR. The pooled IRR of haematological malignancies in PsA overall vs. the general population was 1.35 (1.17 to 1.55). Throughout, the estimates were largely similar for lymphoid and myeloid malignancies (Figure 1). The crude IR of haematological malignancies were substantially akin across different TNFi agents.Figure 1.Pooled incidence rate ratios (IRRs) (95% CI) of haematological malignancy overall and by lymphoid and myeloid types, in first ever TNFi treated versus biologics-naïve patients with PsA, and versus general population comparators. Legend: Lymphoid malignancies include international classification of diseases (ICD) 10 codes C81-86, C88, C90-91. Myeloid malignancies include ICD10 codes C92-95, D45-D46, D47.1, D47.3-5. Incidence rate ratios adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ConclusionIn this large five-country cohort study, we did not observe any increased risk of haematological malignancies overall, nor for lymphoid and myeloid types, in patients with PsA treated with TNFi. By contrast, there were signals of a moderately increased underlying risk of haematological malignancies, both of lymphoid and myeloid types, in patients with PsA overall as compared to the general population. The findings are of importance from a patient information perspective.AcknowledgementsWe would like to acknowledge the NordForsk and FOREUM, and especially the patient representatives of the NordForsk collaboration for their valuable contribution to this study.Disclosure of InterestsRené Cordtz: None declared, Johan Askling Consultant of: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Bénédicte Delcoigne: None declared, Karin Ekström Smedby: None declared, Eva Baecklund: None declared, Christine Ballegaard: None declared, Pia Isomäki Speakers bureau: AbbVie, Eli Lilly and Pfizer, Consultant of: AbbVie, Eli Lilly, Pfizer, Roche and ViforPharma, Grant/research support from: Pfizer, Kalle Aaltonen: None declared, Björn Gudbjornsson Speakers bureau: Novartis, not related to this work, Consultant of: Novartis, not related to this work, Thorvardur Love Speakers bureau: Celgene, Sella Aa. Provan: None declared, Brigitte Michelsen Grant/research support from: Novartis, not related to this work, Joe Sexton: None declared, Lene Dreyer Speakers bureau: Eli Lilly, Galderma and Janssen, Grant/research support from: BMS not related to this work, Karin Hellgren: None declared
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| 8. |
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| 9. |
- Ekberg, S., et al.
(författare)
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Myocardial infarction in diffuse large B-cell lymphoma patients - a population-based matched cohort study
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:5, s. 1048-1060
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Tidskriftsartikel (refereegranskat)abstract
- Background The outcome for diffuse large B-cell lymphoma (DLBCL) patients has improved with the immunochemotherapy combination R-CHOP. An increased rate of heart failure is well documented following this treatment, whereas incidence and outcome of other cardiac complications, for example myocardial infarction, are less well known. Method We identified 3548 curatively treated DLBCL patients in Sweden diagnosed between 2007 and 2014, and 35474 matched lymphoma-free general population comparators. The incidence, characteristics and outcome of acute myocardial infarctions (AMIs) were assessed using population-based registers up to 11 years after diagnosis. The rate of AMI was estimated using flexible parametric models. Results Overall, a 33% excess rate of AMI was observed among DLBCL patients compared with the general population (HR: 1.33, 95% CI: 1.14-1.55). The excess rate was highest during the first year after diagnosis and diminished after 2 years. High age, male sex and comorbidity were the strongest risk factors for AMI. Older patients (>70 years) with mild comorbidities (i.e. hypertension or diabetes) had a 61% higher AMI rate than comparators (HR: 1.61, 95% CI: 1.10-2.35), whereas the corresponding excess rate was 28% for patients with severe comorbidities (HR: 1.28, 95% CI: 1.01-1.64). Among younger patients (<= 70), a short-term excess rate of AMI was limited to those with severe comorbidities. There was no difference in AMI characteristics, pharmacological treatment or 30-day survival among patients and comparators. Conclusion DLBCL patients have an increased risk of AMI, especially during the first 2 years, which calls for improved cardiac monitoring guided by age and comorbidities. Importantly, DLBCL was not associated with differential AMI management or survival.
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| 10. |
- Harrysson, S., et al.
(författare)
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Outcomes of relapsed/refractory diffuse large B-cell lymphoma and influence of chimaeric antigen receptor T trial eligibility criteria in second line-A population-based study of 736 patients
- 2022
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 198:2, s. 267-277
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Tidskriftsartikel (refereegranskat)abstract
- Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). To estimate the benefit of these therapies in the real-world setting, comprehensive data on patients treated in clinical routine are needed. We report outcomes for 736 R/R DLBCL patients identified among all curatively treated DLBCL patients in Sweden in the period 2007-2014. Survival and associations with disease characteristics, second-line treatment and fulfilment of chimaeric antigen receptor (CAR) T-cell trial criteria were assessed. Median overall survival (OS) was 6.6 months (<= 70 years 9.6 months, >70 years 4.9 months). Early relapse (<= 12 months) was strongly associated with selection of less intensive treatment and poor survival. Among patients of at most 70 years of age, 63% started intensive second-line treatment and 34% received autologous stem cell transplantation (ASCT). Two-year OS among transplanted patients was 56% (early relapse <= 12 months 40%, late relapse >12 months 66%). A minority of patients 76 years (n = 178/506, 35%) fitted CAR T trial criteria. Median progression-free survival (PFS) for patients with early relapse fitting trial criteria was 4.8 months. In conclusion, most R/R DLBCL manifest early and are often ineligible for or cannot complete intensive regimens resulting in dismal survival. Real-world patients eligible for CAR T trials also did poorly, providing a benchmark for efficacy of novel therapies.
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| 11. |
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| 12. |
- Hu, Kejia, et al.
(författare)
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Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis : a nationwide register-based cohort study
- 2020
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown.METHODS: We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis.RESULTS: Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98).CONCLUSION: Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.
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| 13. |
- Khoei, NS, et al.
(författare)
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Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin’s lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin’s lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated (p < 5 × 10−8) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 (UGT1A1) gene explained 16.9% and the remaining 114 SNPs (non-UGT1A1 SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non-UGT1A1 SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin’s lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73–0.99, P 0.04 and OR 0.64, 95% CI 0.42–0.99, p 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04–1.20, p 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin’s lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.
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| 17. |
- Mansouri, L, et al.
(författare)
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Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
- 2023
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 37:2, s. 339-347
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
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| 18. |
- Moore, Amy, et al.
(författare)
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Genetically Determined Height and Risk of Non-hodgkin Lymphoma
- 2020
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Ingår i: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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| 19. |
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| 20. |
- Shen, Qing, et al.
(författare)
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NSAID use and unnatural deaths after cancer diagnosis : a nationwide cohort study in Sweden
- 2022
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer patients experience increased risk of death from accident and suicide. Cognitive impairment induced by cancer-related inflammation and stress-related psychiatric symptoms may be underlying mechanisms. We therefore studied the association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of these outcomes.METHODS: Following a cohort of 388,443 cancer patients diagnosed between October 2005 and December 2014 in Sweden, we ascertained dispense of aspirin or non-aspirin NSAIDs from 3 months before cancer diagnosis onward and defined the on-medication period as from date of drug dispense until the prescribed dosage was consumed. Follow-up time outside medicated periods and time from unexposed patients were defined as off-medication periods. We used Cox models to estimate hazard ratios (HRs) of death due to suicide or accident, by comparing the on-medication periods with off-medication periods.RESULTS: In total, 29.7% of the cancer patients had low-dose aspirin dispensed and 29.1% had non-aspirin NSAIDs dispensed. Patients with aspirin use were more likely to be male than patients without aspirin use. Compared with off-medication periods, there was a 22% lower risk of accidental death (N = 651; HR 0.78, 95% confidence interval [CI]: 0.70 to 0.87) during on-medication periods with aspirin. The use of aspirin was not associated with risk of suicide (N = 59; HR 0.96, 95% CI: 0.66 to 1.39). No association was noted between use of non-aspirin NSAIDs and the risk of suicide (N = 13; HR 0.95, 95% CI: 0.42 to 2.18) or accidental death (N = 59; HR 0.92, 95% CI: 0.68 to 1.26).CONCLUSIONS: Intake of low-dose aspirin after cancer diagnosis was associated with a lower risk of unnatural deaths among cancer patients.
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| 21. |
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| 22. |
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| 23. |
- Entrop, Joshua P., et al.
(författare)
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Reproduction patterns among classical Hodgkin lymphoma survivors treated with BEACOPP and ABVD in Sweden, Denmark and Norway-A population-based matched cohort study
- 2023
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 153:4, s. 723-731
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Tidskriftsartikel (refereegranskat)abstract
- Childbirth rates in classical Hodgkin lymphoma (cHL) survivors have historically been reduced compared to the general population. Understanding if contemporary treatment protocols are associated with reduced fertility is crucial as treatment guidelines shift toward more liberal use of intensive chemotherapy. We identified 2834 individuals aged 18-40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital diagnosed 1995-2018, who were linked to national medical birth registers. Cox regression adjusted for stage, performance status, year, and age at diagnosis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) contrasting time to first childbirth by treatment groups (ABVD, 2-4 BEACOPP, 6-8 BEACOPP) up to 10 years after diagnosis. Overall, 74.8% of patients were treated with ABVD, 3.1% with 2-4 BEACOPP and 11.2% with 6-8 BEACOPP. Adjusted HRs comparing childbirth rates in individuals treated with 6-8 BEACOPP, and 2-4 BEACOPP to ABVD were 0.53 (CI: 0.36-0.77) and 0.33 (CI: 0.12-0.91) for males, and 0.91 (CI: 0.61-1.34) and 0.38 (CI: 0.12-1.21) for females. Cumulative incidence of childbirths after 10 years was 19.8% (CI: 14.5%-27.0%) for males and 34.3% (CI: 25.8%-45.6%) for females treated with 6-8 BEACOPP. Proportions of children born after assisted reproductive technique (ART) treatments were 77.4% (CI: 60.2-88.6%) for males following 6-8 BEACOPP, and <11% for females. Among ABVD treated patients the corresponding proportions were 12.2% (CI: 8.5%-17.3%) and 10.6% (CI: 7.4%-14.9%). BEACOPP treatment is associated with decreased childbirth rates compared to ABVD in male, but not female, cHL patients, despite widespread access to ART in the Nordics.
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| 24. |
- Entrop, Joshua P., et al.
(författare)
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Reproduction patterns among non-Hodgkin lymphoma survivors by subtype in Sweden, Denmark and Norway : A population-based matched cohort study
- 2023
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 202:4, s. 785-795
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies concerning reproductive patterns among non-Hodgkin lymphoma (NHL) survivors are scarce and those available have reported conflicting results. Treatment regimens vary considerably between aggressive and indolent NHL and studies of reproductive patterns by subtypes are warranted. In this matched cohort study, we identified all NHL patients aged 18-40 years and diagnosed between 2000 and 2018 from the Swedish and Danish lymphoma registers, and the clinical database at Oslo University Hospital (n = 2090). Population comparators were matched on sex, birth year and country (n = 19 427). Hazard ratios (HRs) were estimated using Cox regression. Males and females diagnosed with aggressive lymphoma subtypes had lower childbirth rates (HRfemale: 0.43, 95% CI: 0.31-0.59, HRmale: 0.61, 95% CI: 0.47-0.78) than comparators during the first 3 years after diagnosis. For indolent lymphomas, childbirth rates were not significantly different from comparators (HRfemale: 0.71, 95% CI: 0.48-1.04, HRmale: 0.94, 95% CI: 0.70-1.27) during the same period. Childbirth rates reached those of comparators for all subtypes after 3 years but the cumulative incidence of childbirths was decreased throughout the 10-year follow-up for aggressive NHL. Children of NHL patients were more likely to be born following assisted reproductive technology than those of comparators, except for male indolent lymphoma patients. In conclusion, fertility counselling is particularly important for patients with aggressive NHL.
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| 25. |
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| 26. |
- Guha, Indranil, et al.
(författare)
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A comparative study of trabecular bone micro-structural measurements using different CT modalities
- 2020
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 65:23, s. 235029-
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis, characterized by reduced bone mineral density and micro-architectural degeneration, significantly enhances fracture-risk. There are several viable methods for trabecular bone micro-imaging, which widely vary in terms of technology, reconstruction principle, spatial resolution, and acquisition time. We have performed an excised cadaveric bone specimen study to evaluate different computed tomography (CT)-imaging modalities for trabecular bone micro-structural analysis. Excised cadaveric bone specimens from the distal radius were scanned using micro-CT and four in vivo CT imaging modalities: high-resolution peripheral quantitative computed tomography (HR-pQCT), dental cone beam CT (CBCT), whole-body multi-row detector CT (MDCT), and extremity CBCT. A new algorithm was developed to optimize soft thresholding parameters for individual in vivo CT modalities for computing quantitative bone volume fraction maps. Finally, agreement of trabecular bone micro-structural measures, derived from different in vivo CT imaging, with reference measures from micro-CT imaging was examined. Observed values of most trabecular measures, including trabecular bone volume, network area, transverse and plate-rod micro-structure, thickness, and spacing, for in vivo CT modalities were higher than their micro-CT-based reference values. In general, HR-pQCT-based trabecular bone measures were closer to their reference values as compared to other in vivo CT modalities. Despite large differences in observed values of measures among modalities, high linear correlation (r ∈ [0.94 0.99]) was found between micro-CT and in vivo CT-derived measures of trabecular bone volume, transverse and plate micro-structural volume, and network area. All HR-pQCT-derived trabecular measures, except the erosion index, showed high correlation (r ∈ [0.91 0.99]). The plate-width measure showed a higher correlation (r ∈ [0.72 0.91]) among in vivo and micro-CT modalities than its counterpart binary plate-rod characterization-based measure erosion index (r ∈ [0.65 0.81]). Although a strong correlation was observed between micro-structural measures from in vivo and micro-CT imaging, large shifts in their values for in vivo modalities warrant proper scanner calibration prior to adopting in multi-site and longitudinal studies.
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| 27. |
- Harrysson, S., et al.
(författare)
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Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden
- 2021
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 28. |
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| 29. |
- Jakobsen, Lasse H., et al.
(författare)
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Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy : an international study of 264 real-world patients
- 2020
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:4, s. 661-671
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Tidskriftsartikel (refereegranskat)abstract
- Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: −0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.
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| 30. |
- Jansson, Anna. K., et al.
(författare)
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Risk and mortality of testicular cancer in patients with neurodevelopmental or other psychiatric disorders
- 2023
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 128:12, s. 2261-2269
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBoth testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT.MethodThis is a nested case-control study including 6166 TGCT patients diagnosed during 1992-2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death.ResultsHistory of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09-2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death.ConclusionsWe report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders.
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| 31. |
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| 32. |
- Ovlisen, Andreas K., et al.
(författare)
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Parenthood Rates and Use of Assisted Reproductive Techniques in Younger Hodgkin Lymphoma Survivors : A Danish Population-Based Study
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:31, s. 3463-3472
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The majority of young adults with Hodgkin lymphoma (HL) are cured, but chemotherapy-induced infertility can have profound psychosocial consequences. Providing data on parenthood rates and use of assisted reproductive techniques (ARTs) after contemporary HL treatment is important for patient counseling and survivorship care.MATERIALS AND METHODS All Danish patients with HL diagnosed during 2000-2015 at the ages 18-40 years who achieved remission after first-line therapy were included and matched on age, sex, and parenthood status to five random persons from the general population. Parenthood rates were defined as the rate of first live birth per 1,000 person years, starting 9 months after HL diagnosis. Nationwide birth and patient registers were used to capture parenthood outcomes and ARTs use.RESULTS A total of 793 HL survivors and 3,965 comparators were included (median follow-up 8.7 years). Similar parenthood rates were observed for male and female HL survivors when compared with matched comparators (56.2 v 57.1; P = .871 for males and 63.8 v 61.2; P = .672 for females). For male HL survivors, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) therapy was associated with lower parenthood rates as compared to the matched comparators (28.1 v 60.8; P = .020). Live birth after ARTs were more common for HL survivors than for comparators (males 21.6% v 6.3%; P < .001; females 13.6% v 5.5%; P = .001). There were no differences in gestational age, Apgar score, or newborn measurements between HL survivors and matched comparators.CONCLUSION The parenthood rates for HL survivors who have not experienced relapse were generally similar to the general population. However, ARTs were used more often before the first live birth in HL survivors, which is relevant information when discussing possible long-term side effects and fertility-preserving treatment options.
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| 33. |
- Petersson, Josefin, et al.
(författare)
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Increasing incidence of colorectal cancer among the younger population in Sweden
- 2020
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Ingår i: Bjs Open. - : Oxford University Press (OUP). - 2474-9842. ; 4:4, s. 645-658
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of colorectal cancer in patients aged less than 50 years is increasing in Western countries. This population-based study investigated the age- and sex-specific incidence of colorectal cancer over time in Sweden, and characterized trends in tumour localization and stage at diagnosis. Methods Patients diagnosed with colorectal cancer between 1970 and 2016 were identified from the Swedish Cancer Registry, and categorized by sex, age and tumour location. The incidence and average annual percentage change (AAPC) were estimated and compared between age groups. Results There was an overall increase in the incidence of colorectal cancer between 1970 and 2006, but a decrease in 2006-2016 (AAPC -0.55 (95 per cent c.i. -1.02 to -0.07) per cent). The largest increase in colonic cancer was in 1995-2005 in women aged less than 50 years (AAPC 2.30 (0.09 to 4.56) per cent versus 0.04 (-1.35 to 1.44) and - 0.67 (-1.62 to 0.28) per cent in women aged 50-74 and 75 years or more respectively). Since 1990, rectal cancer increased in patients of both sexes aged below 50 years, with higher AAPC values in women (2006-2016: 2.01 (-1.46 to 5.61) per cent versus 0.20 (-2.25 to 2.71) per cent in men). Younger patients were more likely than those aged 50-74 and 75 years or more to present with stage III-IV colonic (66.2, 57.6 and 49.6 per cent respectively) and rectal (61.2, 54.3 and 51.3 per cent) cancer. From the mid 1990s, rates of proximal and distal colorectal cancer, and rectal cancer were increased in patients aged less than 50 years. Conclusion The overall incidence of colorectal cancer in Sweden decreased in the past decade. However, in patients under 50 years of age the incidence of colorectal cancer - proximal, distal and rectal - continued to increase over time.
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| 34. |
- Poulakis, K, et al.
(författare)
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Multi-cohort and longitudinal Bayesian clustering study of stage and subtype in Alzheimer's disease
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4566-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding Alzheimer’s disease (AD) heterogeneity is important for understanding the underlying pathophysiological mechanisms of AD. However, AD atrophy subtypes may reflect different disease stages or biologically distinct subtypes. Here we use longitudinal magnetic resonance imaging data (891 participants with AD dementia, 305 healthy control participants) from four international cohorts, and longitudinal clustering to estimate differential atrophy trajectories from the age of clinical disease onset. Our findings (in amyloid-β positive AD patients) show five distinct longitudinal patterns of atrophy with different demographical and cognitive characteristics. Some previously reported atrophy subtypes may reflect disease stages rather than distinct subtypes. The heterogeneity in atrophy rates and cognitive decline within the five longitudinal atrophy patterns, potentially expresses a complex combination of protective/risk factors and concomitant non-AD pathologies. By alternating between the cross-sectional and longitudinal understanding of AD subtypes these analyses may allow better understanding of disease heterogeneity.
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| 35. |
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| 36. |
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| 37. |
- Vasaitis, Lilian, et al.
(författare)
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Population-based study of patients with primary Sjögren’s syndrome and lymphoma : lymphoma subtypes, clinical characteristics, and gender differences
- 2020
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 49:3, s. 225-232
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine lymphoma subtypes, clinical characteristics, and gender differences in patients with primary Sjögren’s syndrome (pSS) and lymphoma in a population-based setting. Method: Patients with Sjögren’s syndrome and lymphoma diagnoses were identified by linkage of the Swedish Patient Register 1964–2007 with the Cancer Register 1990–2007. Clinical data were collected from medical records and lymphoma tissues were re-examined. The lymphoma subtype distribution was compared with the Swedish Lymphoma Register. Results: We identified 105 pSS patients with lymphoma. Diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma [MZL including mucosa-associated lymphoid tissue (MALT) lymphoma] (31%) were the most common lymphoma subtypes. The proportion of DLBCL was not increased compared to the general population reference (32%, p = 1), in contrast to MZL (general population 5%, p < 0.0001). Compared to DLBCL, MALT lymphoma was diagnosed at a younger age (55 vs 67 years, p = 0.0001), and earlier after patient-reported sicca onset (7 vs 18 years, p = 0.0001) and pSS diagnosis (2 vs 9 years, p = 0.0005). Sixteen of the pSS-lymphoma cases were men (15%), twice the proportion in general pSS populations. Compared to women, men had a shorter median time from pSS diagnosis to lymphoma diagnosis (1 vs 8 years, p = 0.0003) and more often had lymphoma in the salivary glands (56% vs 29%, p = 0.04). Conclusion: DLBCL and MZL are common in pSS patients, but only MZL/MALT lymphoma occurs at an increased relative frequency in pSS compared to the general population. The study supports increased awareness of signs of lymphoma in men in the first years after pSS diagnosis.
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| 38. |
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| 39. |
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| 40. |
- Wästerlid, Tove, et al.
(författare)
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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
- 2020
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 95:7, s. 740-748
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 41. |
- Zeng, EW, et al.
(författare)
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Adjuvant Hormone Therapy-Related Hot Flashes Predict Treatment Discontinuation and Worse Breast Cancer Prognosis
- 2022
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Ingår i: Journal of the National Comprehensive Cancer Network : JNCCN. - : Harborside Press, LLC. - 1540-1413 .- 1540-1405. ; 20:6, s. 683-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical trials have shown that adjuvant hormone therapy (AHT)–related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting. Patients and Methods: By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes. Results: Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11–2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21–1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41–2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39–2.35) or died from cancer (HR, 1.71; 95% CI, 1.37–2.12). Conclusions: AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.
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| 42. |
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