Occurrence of Comorbidities before and after Soft Tissue Sarcoma Diagnosis

Background. Data is limited on the burden of common comorbidities, such as cardiovascular disease (CVD), respiratory disease and diabetes, or comorbidities related to cancer and its treatment, such as anemia and depression, in patients with soft tissue sarcoma (STS). Patients and Methods. From the Dutch Pathology Registry linked to the PHARMO database (including data on drug use and hospitalizations), 533 patients with STS were selected during 2000–2007 and matched 1 : 10 to cancer-free controls. The occurrences of comorbidities were assessed in the 12 months before and after STS diagnosis. Results. STS patients were 2–4 times more likely to have comorbidities at diagnosis compared with cancer-free controls. The incidence of CVD, anemia, and depression after STS diagnosis differed significantly from cancer-free controls and decreased during followup from 40–124 per 1,000 person-years (py) during the first six months to 11–38 per 1,000 py more than 12 months after diagnosis. The incidence of respiratory disease and diabetes among STS patients remained stable during followup (5–21 per 1,000 py) and did not differ significantly from cancer-free controls. Conclusions. STS patients were more likely to have comorbidities before cancer diagnosis and to develop CVD, anemia, and depression after diagnosis compared to cancer-free controls

The influence of BRAF and KRAS mutation status on the association between aspirin use and survival after colon cancer diagnosis

Background: Use of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis. Methods: A random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined. Data on aspirin use (80 mg) were obtained from the PHARMO Database Network. Parametric survival models with exponential (Poisson) distribution were used. Results: Aspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60 (95% CI 0.44-0.83). In contrast, aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% CI 0.57-2.16). P-value for interaction was non-significant. KRAS mutational status did not differentiate in the association between aspirin use and survival. Conclusion: Low-dose aspirin use after colon cancer diagnosis was associated with improved survival in BRAF wild-type tumors only. However, the large confidence interval of the rate ratio for the use of aspirin in patients with BRAF mutation does not rule out a possible benefit. These results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future

Myocardial infarction, ischaemic stroke and pulmonary embolism before and after breast cancer hospitalisation. A population-based study.

We studied the occurrence of myocardial infarction (MI), ischaemic stroke (IS) and pulmonary embolism (PE) before and after breast cancer hospitalisation compared with cancer-free controls. For this, women with a first breast cancer hospitalisation during 2000-2007 were selected from the PHARMO Record Linkage System, including drug use and hospitalisations of three million inhabitants in the Netherlands, and matched 1:10 by age to cancer-free women. The occurrence of MI, IS and PE were assessed in the 12 months before and after breast cancer hospitalisation. The study included 11,473 breast cancer patients, with a mean (± SD) age of 59 (± 14) years. Breast cancer patients were two to three times as likely as their cancer-free controls to have had a hospitalisation for PE, MI or IS in the 12 months before diagnosis, though prevalence was <1% in all groups. Breast cancer patients experienced an extreme high risk of PE in the first six months after diagnosis (hazard ratio [HR] 23.5, 95% confidence interval [CI] 11.1-49.7 compared to controls), which declined gradually to a four times increased risk (HR 3.6, 95%CI 2.4-5.5) more than 12 months after breast cancer hospitalisation. However, incidence was low: less than five events per 1,000 person years during all time periods. For MI and IS we did not observe significant increased HRs after breast cancer hospitalisation compared to controls. Breast cancer patients seem to have a higher risk profile to develop MI and IS, and receive treatment that increases the risk of PE compared to cancer-free controls, although the frequency of hospitalisations was low

Half of breast cancer patients discontinue tamoxifen and any endocrine treatment before the end of the recommended treatment period of 5 years: a population-based analysis

Observational studies on long-term endocrine treatment among breast cancer patients have presented discontinuation rates on tamoxifen, but lack information on the continuance of any endocrine treatment [both tamoxifen and aromatase inhibitors (AIs)] within the same cohort. In this study we determined switching rates from tamoxifen to AIs, discontinuation rates of tamoxifen only, discontinuation rates of any endocrine treatment and determinants of first treatment switch and treatment discontinuation. Patients with early stage breast cancer (stage I-IIIa) starting on tamoxifen were selected from the linked Eindhoven Cancer Registry-PHARMO RLS cohort in the period 1998-2006. Continuous use (allowing a 60 days gap between refills) of tamoxifen only and any endocrine treatment were determined after various follow-up periods: 1, 2, 3, 4, and 5 years. Time to first switch from tamoxifen to an AI was assessed. Cox regression was used to identify determinants of first treatment switch, discontinuation of tamoxifen, and discontinuation of any endocrine treatment. A total of 1,451 new early stage breast cancer patients started on tamoxifen. Of those, 380 had a treatment switch to an AI during follow-up. Of the patients followed for 5 years, 40% continuously used tamoxifen, which was 49% for any endocrine treatment. Older age (older than 70 versus 50-69 years) was independently associated with increased discontinuation of tamoxifen and any endocrine therapy. Patients with two or more concomitant diseases (versus no comorbidity) showed an increased likelihood to stop any endocrine treatment or switch treatment from tamoxifen to an AI. In conclusion, up to half of the breast cancer patients starting tamoxifen continued 5 years of endocrine treatment. Identification of patients at risk of discontinuation will assist in the development of interventions to improve treatment continuation comparable to that of patients included in clinical trials

Pharmaceutically treated anxiety but not depression prior to cancer diagnosis predicts the onset of cardiovascular disease among breast cancer survivors

Purpose: To examine the associations between pharmaceutically treated anxiety and depression present in the year prior to breast cancer diagnosis and the risk of incident cardiovascular disease (CVD), while controlling for traditional cardiovascular risk factors and clinical characteristics in a population-based observational study. Methods: Adult 1-year breast cancer survivors (n = 7227), diagnosed between 01-01-1999 and 12-31-2010, with no history of CVD, were selected from the Netherlands Cancer Registry. Drug dispensing data were derived from the PHARMO Database Network and used as proxy for CVD, anxiety, and depression. By multivariable Cox regression analysis, we examined the risk associated with pharmaceutically treated anxiety and depression for developing CVD after cancer diagnosis, adjusting for age, pharmaceutically treated hypertension, hypercholesterolemia, and diabetes mellitus in the year prior to cancer diagnosis, tumor stage, and cancer treatment. Results: During the 13-year follow-up period, 193 (3%) breast cancer survivors developed CVD. Women pharmaceutically treated for anxiety in the year prior to their cancer diagnosis had a 48% increased hazard for CVD [HR = 1.48; 95% CI 1.05-1.08] after full adjustment. This association was restricted to breast cancer survivors who were 65 years or younger. Depression was not associated with CVD risk [HR = 0.89; 95% CI 0.52-1.53]. Older age [HR = 1.06; 95% CI 1.05-1.08], hypertension [HR = 1.80; 95% CI 1.32-2.46], and hypercholesterolemia [HR = 1.63; 95% CI 1.15-2.33] were associated with an increased hazard for incident CVD, whereas hormone therapy [HR = 0.59; 95% CI 0.42-0.83] was protective. Conclusion: Anxiety present in the year prior to breast cancer diagnosis increases the risk of incident CVD in 1-year breast cancer survivors, after adjustment for depression, traditional cardiovascular risk factors, and clinical characteristic

Prescriber Compliance With Liver Monitoring Guidelines for Pazopanib in the Postapproval Setting : Results From a Distributed Research Network

OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. METHODS: Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network. Measures of prescriber compliance were designed using the original pazopanib label guidelines for liver monitoring. RESULTS: Results from the VA (n = 288) and oncology databases (n = 283) indicate that prescriber liver chemistry monitoring was less than 100%: 73% to 74% compliance with baseline testing and 37% to 39% compliance with testing every 4 weeks. Compliance was highest near drug initiation and decreased over time. Among patients who should have had weekly testing, the compliance was 56% in both databases. The more serious elevations examined, including combinations of liver enzyme elevations meeting the laboratory definition of Hy's law were infrequent but always led to appropriate discontinuation of pazopanib. Only 4 patients were identified for analysis in the Dutch database; none had recorded baseline testing. CONCLUSIONS: In this population-based study, prescriber compliance was reasonable near pazopanib initiation but low during subsequent weeks of treatment. This study provides information from real-world community practice settings and offers feedback to regulators on the effectiveness of label monitoring guidelines.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal