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Hilde Jensvoll,1,2 Marianne T Severinsen,3,4 Jens Hammerstrøm,5 Sigrid K Brækkan,1,2 Søren R Kristensen,4,6 Suzanne C Cannegieter,7 Kristine Blix,1,2 Anne Tjønneland,8 Frits R Rosendaal,1,7,9 Olga Dziewiecka,1 Kim Overvad,10,11 Inger Anne Næss,12 John-Bjarne Hansen1,21Department of Clinical Medicine, KG Jebsen – Thrombosis Research and Expertise Center (TREC), UiT – The Arctic University of Norway, 2Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway; 3Department of Hematology, Aalborg University Hospital, 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 6Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark; 7Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; 8Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; 9Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands; 10Department of Cardiology, Aalborg University Hospital, Aalborg, 11Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; 12Department of Hematology, Trondheim University Hospital, Trondheim, NorwayBackground: Although venous thromboembolism (VTE) is a known common complication in cancer patients, there is limited knowledge on patient-related and cancer-specific risk factors in the general population. The Scandinavian Thrombosis and Cancer (STAC) Cohort was established by merging individual data from three large Scandinavian cohorts (The Tromsø Study, the second Nord-Trøndelag Health Study, and the Danish Diet, Cancer and Health Study). Here, we present the profile of the STAC cohort and provide age-specific incidence rates of VTE and cancerMethods: The STAC cohort includes 144,952 subjects aged 19–101 years without previous VTE or cancer. Baseline information collected in 1993–1997 included physical examination, self-administered questionnaires, and blood samples. Validated VTE events and cancer diagnoses were registered up to 2007–2012.Results: There were 2,444 VTE events (1.4 per 1,000 person-years [PY]) during follow-up, and the incidence increased exponentially from 0.3 per 1,000 PY in subjects aged 20–29 years to 6.4 per 1,000 PY in subjects aged 80+. Overall, 51% of the VTE events were provoked, and cancer was the most common provoking factor (19%), followed by immobilization and surgery (both 15%). In total, 19,757 subjects developed cancer during follow-up (9.8 per 1,000 PY), and the 5-year age-specific incidence rates of cancer were coherent with corresponding rates from the Norwegian Cancer Registry.Conclusion: The STAC cohort will provide a unique opportunity to explore the epidemiology and impact of genetic and environmental patient-related and cancer-specific risk factors for VTE in the general population.Keywords: venous thromboembolism, incidence rates, person-years, pulmonary embolism, population-based cohort, prospective, cancer

Introduction: Treatment of lymphoma can be associated with cognitive challenges, and some patients may fear development of dementia as long-term complication. Studies report a lower risk of dementia after cancer. Some believe this difference to be a protective mechanism of cancer, others believe it to be driven by bias. The risk of developing dementia after lymphoma has not been investigated in a population-based setting. The aim of this study was to identify the risk of being diagnosed with dementia after lymphoma treatment., Materials and Methods: This Danish nationwide matched cohort study included patients aged ≥65 years with a first-time diagnosis of a non-central nervous system lymphoma between 2005 and 2018 in complete remission after treatment with chemotherapy. Patients diagnosed with dementia or treated with dementia medication before lymphoma diagnosis were excluded. Each patient was matched 1:5 on sex, year of birth, and a modified Charlson comorbidity index. Patients and matched comparators were followed from the corresponding patient's date of complete remission. The risk of developing dementia was calculated using cause-specific hazard ratios (HR), and the cumulative risk was estimated by Aalen-Johansen with death as the competing risk., Results: A total of 3,244 patients and 16,220 matched comparators were included in the study. There was no difference in risk of all-cause dementia among patients with lymphoma compared to matched comparators with cause-specific HR of 0.85 (95% confidence interval [CI]: 0.70;1.04). The risk of both Alzheimer's disease and non-Alzheimer's dementia was equal among patients and comparators: HR 0.89 (95% CI: 0.66;1.21) and 0.82 (95% CI: 0.63;1.07), respectively. Stratified by lymphoma subtype, age, or year of diagnosis, the risk of all-cause dementia remained equal among patients and matched comparators. The cumulative risk of all-cause dementia was significantly lower among patients with lymphoma compared to matched comparators (Gray's test p < 0.001), probably reflecting higher mortality in patients with lymphoma., Discussion: The risk of all-cause dementia, Alzheimer's disease, and non-Alzheimer's dementia was equal among older patients with lymphoma compared to matched comparators. Our data suggests that risk of developing dementia is not changed after lymphoma treatment., Competing Interests: Declaration of Competing Interest E.F.M., L.H.J., B.M., H.J., K.H.K., R.S.P., A.D-A., C.B.P., A.O.G., T.C.E-G., and M.T.S.: has nothing to declare. J.M.J.: Advisory board/consultancy: Roche, Giled/KITE, Novartis, Celgene/BMS, Abbvie, SOBI, Incyte, and Orion. M.R.C.: Consultancy: Gilead, AstraZeneca, AbbVie, Janssen, and Incyte. Travel Expenses: AbbVie, Genmab, and Roche. Speaker fee: Genmab. T.S.L.: Advisory Board: Roche, Gilead, Novartis, and BMS. P.B.: Advisory board/consultancy: Roche, Gilead and Swedish Orphar (SOBI)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Cisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking., Objective: To evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding., Design Setting and Participants: In a population-based study, 506 men administered first-line CBCT during 2000-2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records., Outcome Measurements and Statistical Analysis: Patients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors., Results and Limitations: Overall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01-3.91), central venous access (OR 2.84, 95% CI 1.46-5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12-5.07) as incident VTE risk factors. Thromboprophylaxis ( n  = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p  = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p  < 0.001)., Conclusions: We found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding., Patient Summary: We found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events., (© 2021 The Author(s).)

Introduction: Venous thromboembolism (VTE) is an important cause of morbidity and mortality in cancer patients, however the risk of VTE differs according to cancer type. Hematological cancers have varying phenotypes. Incidence rates (IR) of VTE in different hematological cancer types have not been investigated in a cancer-exposed subset of the general population., Methods: In a population-based cohort, we estimated incidence rates of VTE among patients with six subtypes of hematological cancer and among age and sex matched reference subjects., Results: During a mean follow-up of 4.8years, 30 objectively confirmed first-time symptomatic VTEs occurred among 838 subjects with hematological cancer. The IR of VTE was higher in all types of cancer except for indolent lymphoma but including chronic lymphocytic leukemia compared with reference subjects both during the first year after cancer diagnosis and 1-5years after diagnosis. IR of VTE for indolent lymphoma was not higher than controls., Conclusion: The IRs of VTE were increased in all types of hematological cancer (including chronic lymphocytic leukemia) compared with reference subjects except indolent lymphomas., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Elevated platelet count is associated with risk of venous thromboembolism in cancer patients initiating chemotherapy. It is not known whether this risk by platelet count is causal or merely reflects the malignant disease. We investigated whether pre-cancer platelet count alone or together with high leukocyte count was associated with risk of venous thromboembolism in subjects who did and did not develop cancer during follow-up in a population-based cohort study., Methods: Platelet count and other baseline characteristics were measured in 25160 initially cancer-free subjects who participated in the Tromsø Study in 1994-1995. Incident cancer and symptomatic venous thromboembolism events were registered up to December 31st, 2009. Multivariable Cox regression models were used to calculate hazard ratio for venous thromboembolism across categories of platelet count (<40th, 40-80th, and >80th percentile) with 95% confidence interval., Results: During follow-up, 2082 subjects were diagnosed with cancer. Platelet count was measured on average 8.3 years before the cancer diagnosis. There were 129 venous thromboembolism events in the cancer cohort (13.5 per 1000 person-years) and 377 in the non-cancer cohort (1.2 per 1000 person-years). In cancer patients, pre-cancer platelet count above the 80th percentile (≥295×10(9)/L) was associated with a 2-fold higher risk of venous thromboembolism (Hazard ratio: 1.98, 95% confidence interval 1.21-3.23) compared to platelet count below the 40th percentile (<235×10(9)/L). Concomitant high platelet and leukocyte counts showed a synergistic effect on the VTE risk. In cancer-free subjects, no association was found., Comment: In conclusion, pre-cancer platelet count was associated with risk of symptomatic venous thromboembolism in cancer patients, but not in cancer-free subjects. Our findings suggest that platelet count and platelet-leukocyte interactions may play a role in the pathogenesis of cancer-related venous thromboembolism.

Background: Elevated white blood cell (WBC) count is associated with risk of venous thromboembolism (VTE) in cancer patients initiating chemotherapy. It is not known whether the risk of VTE by WBC count in cancer patients is causal or merely a consequence of the malignant disease. To address this question, we studied the association between WBC count, measured prior to cancer development, and risk of VTE in subjects who did and did not develop cancer during follow-up in a prospective population-based study., Methods: Baseline characteristics, including WBC and neutrophil counts, were measured in 24304 initially cancer-free subjects who participated in the Tromsø Study in 1994-1995. Incident cancer diagnosis and VTE events were registered up to September 1, 2007. In the cancer cohort, WBC and neutrophil counts were measured in average 7.1 years before cancer development. Cox-regression models were used to calculate hazard ratios (HRs) for VTE by WBC and neutrophil counts as categorized variables (<40(th), 40-80(th), and >80(th) percentile) with 95% confidence intervals (CIs)., Results: During follow-up, 1720 subjects developed cancer and there were 388 VTE events, of which 116 occurred in the cancer-group (6.9 per 1000 person-years) and 272 in the cancer-free group (1.1 per 1000 person-years). In those who developed cancer, WBC count above the 80(th) percentile (≥ 8.6 x 10(9) cells/L) was associated with a 2.4-fold higher risk (HR 2.36, 95% CI: 1.44-3.87) of VTE compared to WBC count below the 40(th) percentile (<6.4 x 10(9) cells/L). No association was found between WBC count and VTE in those who stayed cancer-free (HR 0.94, 95% CI 0.65-1.36). Similar findings were observed for neutrophils., Comment: Pre-cancer WBC count was associated with risk of VTE in cancer patients, but not in cancer-free subjects. Our findings suggest that leukocytes may play a causal role in cancer-related VTE rather than only reflecting the low-grade inflammation associated with cancer.