Purpose:Cancer outcome studies frequently utilize registry data, which provide large-scale population-level information. However, these registries often lack detailed clinical information regarding comorbidities, lifestyle factors, and in-hospital treatments. The Central Denmark Cancer Cohort (CDCC) was established to address these limitations by linking medical and administrative registry data with clinical electronic medical records (EMR), to facilitate research to better understand the clinical course of cancer and its complications. Patients and Methods:The CDCC includes all patients with incident cancer, except non-melanoma skin cancer, diagnosed in the Central Denmark Region between 2012 and 2021, with complete follow-up through December 31, 2021. The CDCC was identified from the Danish Cancer Registry and linked via the Civil Personal Registration number to the Central Denmark Region Clinical Information System (CDRCIS) and to national registries, including the Danish National Patient Registry, National Prescription Registry, and Register of Laboratory Results for Research. We extracted data on demographics, lifestyle factors, comorbidities, treatments, and survival outcomes and assessed the availability of these data. Results:The CDCC included 68,028 patients with a median age of 68 years (interquartile range: 59-76 years); 47.2% were female. The most common cancers were prostate cancer (10,024 patients), breast cancer (9,100 patients), and non-small cell lung carcinoma (7,264 patients). At diagnosis, 98.0% of patients had laboratory test results available, 87.5% received at least one in-hospital medication, and 86.9% had at least one characteristic documented in CDRCIS. During median follow-up of 2.6 years, 37.8% of patients died and five-year survival was 59.0% (95% confidence interval: 58.6-59.4%). Data completeness varied by cancer type. Conclusion:The CDCC integrates clinical, lifestyle, and laboratory data with cancer registry information. By capturing factors typically unavailable in registry-based research, this platform offers a unique foundation for longitudinal studies on the clinical course of cancer.

Patients face an increased risk of cardiovascular disease shortly after a cancer diagnosis, but evidence on long-term risk among cancer survivors remains limited. In this study the authors sought to estimate the risk of cardiovascular disease in cancer survivors previously treated with systemic cancer therapy. Using Danish population-based registries, we identified individuals who had received systemic cancer treatment and were free of both cancer and treatment 3 years after diagnosis (index date). For each cancer survivor, 5 cancer-free individuals from the general population were randomly selected, matched by birth year, sex, and calendar year. Participants were followed from the index date for up to 5 years. HRs were estimated using Cox regression, adjusted for potential confounders. Compared with 457,035 matched individuals, the 91,407 cancer survivors had an increased risk of heart failure or cardiomyopathy (HR: 1.08; 95% CI: 1.02-1.15), venous thromboembolism (HR: 1.50; 95% CI: 1.41-1.61), pericarditis, endocarditis, or myocarditis (HR: 1.30; 95% CI: 1.11-1.52), and kidney failure (HR: 1.17; 95% CI: 1.10-1.25), but not of ischemic heart disease, stroke, or atrial fibrillation. Estimates varied substantially by cancer type and treatment agent. For example, venous thromboembolism risk was consistently increased across nearly all cancer types, whereas hypertension risk was elevated for none. Ischemic heart disease risk was increased only among lung cancer survivors. Stroke was associated with platinum compounds but not with other systemic treatments. Several cardiovascular disease risks were elevated among cancer survivors, with substantial variation by cancer type and treatment.

Importance:Emerging evidence suggests that cholesterol plays a role in breast cancer (BC) metabolism, raising the possibility that cholesterol-lowering medications, such as statins, may improve BC prognosis. Objective:To evaluate the association between postdiagnosis statin initiation and BC mortality using an emulated target trial approach. Design, Setting, and Participants:This observational cohort study using a target trial framework included 96 924 women diagnosed with stage I to III BC from 2000 to 2021 from Nationwide Danish registries, including the Danish Breast Cancer Group's clinical database and the Danish National Prescription Registry. Women with prior invasive BC or prediagnosis use of cholesterol-lowering medication were excluded. Eligible patients were duplicated into a cloned cohort and assigned to 1 of 2 treatment strategies: statin initiation within 36 months postdiagnosis or no statin initiation. Patients were followed up until deviation from the assigned strategy, emigration, death, 10 years of follow-up, or October 5, 2022. Exposures:Initiation of any statin within 36 months after BC diagnosis. Main Outcomes and Measures:The primary outcome was BC mortality. Secondary outcomes included all-cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using inverse probability of censoring weighted (IPCW) Cox regression models with a robust variance estimator. Results:A total of 66 952 patients with BC were enrolled in the emulated target trial (17 152 [27.6%] were aged 50-59 years); 4851 (7.2%) initiated statins within 36 months after diagnosis. Over 606 266 person-years of follow-up, 9130 patients died from BC and 19 679 from any cause. The 10-year risk of breast cancer mortality was 11.8% among statin initiators and 13.5% among noninitiators, corresponding to a risk difference of 1.7% (95% CI, 0.5% to 3.0%). A similar difference was observed for all-cause mortality (23.3% vs 24.5%; risk difference, 1.2%; 95% CI, -0.1% to 2.5%). IPCW analysis yielded an HR of 0.90 (95% CI, 0.85 to 0.95) for BC mortality and 0.92 (95% CI, 0.85 to 1.00) for all-cause mortality among statin initiators vs noninitiators. Conclusions and Relevance:In this cohort study, among 66 952 women with early BC, postdiagnosis statin initiation was associated with a modest reduction in BC and all-cause mortality. These findings support further investigation into the potential role of statins as an adjunct to standard adjuvant BC treatment.

BACKGROUND:Patients face an increased risk of cardiovascular disease shortly after a cancer diagnosis, but evidence on long-term risk among cancer survivors remains limited. OBJECTIVES:In this study the authors sought to estimate the risk of cardiovascular disease in cancer survivors previously treated with systemic cancer therapy. METHODS:Using Danish population-based registries, we identified individuals who had received systemic cancer treatment and were free of both cancer and treatment 3 years after diagnosis (index date). For each cancer survivor, 5 cancer-free individuals from the general population were randomly selected, matched by birth year, sex, and calendar year. Participants were followed from the index date for up to 5 years. HRs were estimated using Cox regression, adjusted for potential confounders. RESULTS:Compared with 457,035 matched individuals, the 91,407 cancer survivors had an increased risk of heart failure or cardiomyopathy (HR: 1.08; 95% CI: 1.02-1.15), venous thromboembolism (HR: 1.50; 95% CI: 1.41-1.61), pericarditis, endocarditis, or myocarditis (HR: 1.30; 95% CI: 1.11-1.52), and kidney failure (HR: 1.17; 95% CI: 1.10-1.25), but not of ischemic heart disease, stroke, or atrial fibrillation. Estimates varied substantially by cancer type and treatment agent. For example, venous thromboembolism risk was consistently increased across nearly all cancer types, whereas hypertension risk was elevated for none. Ischemic heart disease risk was increased only among lung cancer survivors. Stroke was associated with platinum compounds but not with other systemic treatments. CONCLUSIONS:Several cardiovascular disease risks were elevated among cancer survivors, with substantial variation by cancer type and treatment.

Metastatic prostate cancer is incurable, and new therapeutic targets and drugs are urgently needed. Viral infections are associated with several cancer types, but a link between viruses and prostate oncogenesis has not been established. Only recently, an association between human cytomegalovirus (CMV) seropositivity and increased risk of prostate cancer mortality was demonstrated. Here, we show that CMV infection is common in the normal prostate epithelium and in prostate tumor tissue, with 70-92% of tumors being infected. Additionally, we report that commonly studied prostate cancer cell lines are CMV infected. Loss-of-function experiments demonstrate that CMV promotes cell survival, proliferation, and androgen receptor signaling, identifying it as a therapeutic target in castration-sensitive and castration-resistant prostate cancer. Several anti-CMV pharmaceutical compounds in clinical use inhibited cell expansion in prostate cancer models both in vitro and in vivo. We conclude that CMV is common in prostate cancer, promotes core prostate cancer cell programs, and can be inhibited by well-tolerated drugs. These findings motivate investigation into potential clinical benefits of CMV inhibition in the treatment of prostate cancer.

Background: Guidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE). Objectives: We aimed to validate a new cancer-associated thrombosis (CAT) risk score in a population-based healthcare setting. Methods: We used healthcare registry data and electronic medical records from the Central Denmark Region to calculate the new CAT risk score and the guideline- recommended Khorana score in patients with a first-time cancer diagnosis who initiated systemic cancer therapy. Patients were followed for 6 months after initiation of therapy. The outcome was any VTE identified through hospital discharge diagnoses. Discrimination was assessed using C statistics. Results: We included 12 471 patients from 2012 to 2020. Of these, 416 (3.3%) developed VTE. The C statistic was 0.71(95% CI, 0.68-0.74) for the new CAT score and 0.66(95% CI, 0.63-0.70) for the Khorana score. The 6-month cumulative VTE incidence was 5.0% in 6175 patients classified as high risk by the new CAT score compared with 1.7% in 6296 patients classified as low risk. The 6-month cumulative VTE incidence was 5.2% in 4263 patients classified as high risk by the Khorana score compared with 2.4% in 8208 patients classified as low risk. Conclusion: The new CAT score had a discriminatory ability similar to that reported in the derivation study. The C statistic was numerically higher than that of the Khorana score. Our findings support the implementation of the new CAT score to identify ambulatory patients with cancer who are at high risk of VTE.