Cardiovascular Risk Factors and Disease After Male Germ Cell Cancer

Abstract

PURPOSE To analyze the risk of cardiovascular disease (CVD) after treatment of male germ cell cancer (GCC). METHODS Clinical data were extracted from the Danish Testicular Cancer database. For each patient, 10 men matched on date of birth were identified in the Danish normal population by risk-set sampling. Cardiovascular risk factors, CVD, and associated deaths were identified in Danish registries. The association between treatment and outcomes was analyzed by separate Cox models for each outcome. Cancer treatment was included as a time-varying covariate. RESULTS We included 5,185 patients with GCC and 51,850 men in the normal population. Median follow-up was 15.8 years. Treatment with bleomycin-etoposide-cisplatin (BEP; n = 1,819) was associated with increased risks of hypertension and hypercholesterolemia. Hazard ratios (HRs) of CVD < 1 year after initiation of BEP treatment were as follows: myocardial infarction (HR, 6.3; 95% CI, 2.9 to 13.9), cerebrovascular accident (HR, 6.0; 95% CI, 2.6 to 14.1), and venous thromboembolism (HR, 24.7; 95% CI, 14.0 to 43.6). One year after BEP treatment, the risk of CVD decreased to normal levels, but after 10 years, increasing risks were found for myocardial infarction (HR, 1.4; 95% CI, 1.0 to 2.0) and cardiovascular death (HR, 1.6; 95% CI, 1.0 to 2.5). Radiotherapy (n = 780) increased the risk of diabetes at long-term follow-up (HR, 1.4; 95% CI, 1.0 to 2.0) but not that of other outcomes. With surveillance (n = 3,332), cardiovascular risk factors, CVD, and cardiovascular death data were comparable to that of the normal population. CONCLUSION Treatment with BEP was associated with highly increased risks of CVD < 1 year after treatment start and mildly increased risks after 10 years of follow-up. Radiotherapy increased the risk of diabetes but not incident CVD. The risk of CVD in patients followed in a surveillance program was comparable to that of the normal population.

Revised manuscript R2, clean version are serum levels of 25-hydroxy vitamin D reduced following orchiectomy in testicular cancer patients?

“…The over-all cure rate is more than 90 % and most of the patients with GCT will enjoy a long life-expectancy despite the diagnosis of cancer [ 2 ]. Therefore, physicians caring for GCT patients are increasingly looking for long-term consequences of treatment, mainly second malignant neoplasms, cardiovascular disease and endocrinological disorders [ 3 – 5 ]. Recently, dysregulation of the vitamin D metabolism secondary to cancer-related loss of one testicle has come into the focus [ 6 ].…”

Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

“…An increased risk of myocardial infarction (hazard ratio (HR): 6.3 (95% CI: 2.9-13.9)), cerebrovascular morbidity (HR: 6.0 (95% CI: 2.6-14.1)), and venous thromboembolism (HR 24.7 (95% CI: 14.0-43.6)) was identified in patients shortly after treatment with cisplatinbased chemotherapy. Although it decreased to levels of the general population within one year after treatment, the risk of myocardial infarction and cardiovascular disease-related death increased again 10 years after treatment-HR: 1.4 (CI: 1.0-2.0) and HR: 1.6 (CI: 1.0-2.5), respectively [40]. Other works show a 1.5-to 5.7-fold increase in the risk of cardiovascular disease in patients treated with chemotherapy compared to those treated with orchiectomy only [41][42][43].…”

Esomeprazole enhances the effect of ionizing radiation to improve tumor control

“…NCT01069081). For example, a recent study presented at the 2020 American Society of Clinical Oncology (ASCO) reported that administration of PPIs with chemotherapy to triple-negative breast cancer (TNBC) patients was associated with significant pathologic complete response (pCR) rate without adding toxicity (clinical trial # NCT02595372) [ 47 ]. Although the doses of PPI required to achieve plasma concentration of about 100 μM for radiosensitizing activity is higher than the standard antacid dose, it is safely achievable in cancer patients.…”