Dataset Information

Vascular fingerprint tool to identify patients with testicular cancer treated with cisplatin-based chemotherapy at high risk of early cardiovascular events.

ABSTRACT:

Background

Patients with testicular cancer treated with chemotherapy have an increased risk of developing early cardiovascular events. Identification of patients with testicular cancer at a high risk of these events enables the development of preventative strategies. This study validates the vascular fingerprint tool to identify these patients.

Patients and methods

We carried out a multicenter prospective study in patients with metastatic testicular cancer [International Germ Cell Cancer Collaborative Group (IGCCCG) good or intermediate risk; retroperitoneal mass <5 cm]. In eligible patients, the vascular fingerprint was assessed before the start of cisplatin-based chemotherapy, which consists of five risk factors, namely, smoking, overweight (body mass index >25 kg/m²), hypertension (blood pressure >140/90 mmHg), dyslipidemia (fasting cholesterol >5.1 mmol/l or low-density lipoprotein-cholesterol >2.5 mmol/l), and diabetes mellitus (fasting glucose ≥7.0 mmol/l). The presence of three or more risk factors was defined as high-risk vascular fingerprints. A log-rank test was carried out with a cardiovascular event within 1 year after the start of chemotherapy as the primary endpoint.

Results

A total of 196 patients with metastatic testicular cancer were included; 15 patients (8%) developed a cardiovascular event: 4 (2%) arterial events and 11 (6%) venous thrombotic events. Overall, 189 vascular fingerprint scores were available. Patients with a high-risk vascular fingerprint (62/189) had a higher risk of developing a cardiovascular event (hazard ratio 3.27, 95% confidence interval 1.16-9.18; log-rank: P = 0.017). Histological diagnosis, prognosis group, cumulative chemotherapy dose, and retroperitoneal mass size did not differ between patients with or without a cardiovascular event. All patients with an arterial event had a high-risk vascular fingerprint compared with 5/11 patients with a venous event. Overweight was more prevalent in patients with cardiovascular events (87% versus 59%; P = 0.037).

Conclusions

The vascular fingerprint is a validated tool to identify patients with testicular cancer at a high risk of developing early cardiovascular events. This tool can be used to develop preventative strategies with anticoagulant treatment.

SUBMITTER: Meuleman AT

PROVIDER: S-EPMC11298865 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Vascular fingerprint tool to identify patients with testicular cancer treated with cisplatin-based chemotherapy at high risk of early cardiovascular events.

Meuleman A T AT Volders E L D ELD Lubberts S S Kerst J M JM Wymenga A N M ANM Aarts M J B MJB Goncalves M B MB Lefrandt J D JD Steursma G G Meijer J J Nuver J J Gietema J A JA

ESMO open 20240713 7

<h4>Background</h4>Patients with testicular cancer treated with chemotherapy have an increased risk of developing early cardiovascular events. Identification of patients with testicular cancer at a high risk of these events enables the development of preventative strategies. This study validates the vascular fingerprint tool to identify these patients.<h4>Patients and methods</h4>We carried out a multicenter prospective study in patients with metastatic testicular cancer [International Germ Cell ...[more]

PMID: 38996520

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Project description:PurposeBleomycin, etoposide, and cisplatin combination chemotherapy (BEP) improves the survival of patients with testicular cancer, but is associated with potentially life-threatening toxicities like pneumonitis and thromboembolic events. This study explored the effects of physical exercise in patients with testicular cancer during or after BEP-chemotherapy on pulmonary and vascular endothelial toxicity.MethodsIn this post hoc analysis of a multicenter randomized clinical trial (NCT01642680), patients with metastatic testicular cancer scheduled to receive BEP-chemotherapy were randomized to a 24-week exercise intervention, initiated during (group A) or after BEP-chemotherapy (group B). Endpoints were pulmonary function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), lung transfer-coefficient and transfer factor for carbon monoxide (KCO, DLCO) and markers of vascular endothelial dysfunction (von Willebrand factor (vWF) and factor VIII).ResultsThirty patients were included. Post-chemotherapy, patients declined less in FVC, FEV1 and DLCO in group A compared to group B. Post-chemotherapy, vWF and factor VIII were significantly lower in group A compared to group B. After completion of exercise, started either during BEP-chemotherapy or thereafter, no between-group differences were found. At 1-year post-intervention, significant between-group differences were found in favour of group A in DLCO and KCO.ConclusionsPatients who exercised during BEP-chemotherapy better preserved FVC, FEV1 and DLCO, measured directly post-chemotherapy and 1-year post-intervention (DLCO, KCO). This coincided with less increase in vWF and factor VIII measured directly post-chemotherapy. These data support a beneficial role of a physical exercise intervention during BEP-chemotherapy on pulmonary and vascular damage in patients with testicular cancer.Trial registryOptimal Timing of Physical Activity in Cancer Treatment (ACT) Registry URL: https://clinicaltrials.gov/ct2/show/NCT01642680 .Trial registration numberNCT01642680.

Project description:BackgroundCisplatin-based chemotherapy increases the risk of cardiovascular and renal disease.ObjectivesWe aimed to define the time course, pathophysiology, and approaches to prevent cardiovascular disease associated with cisplatin-based chemotherapy.MethodsTwo cohorts of patients with a history of testicular cancer (n = 53) were recruited. Cohort 1 consisted of 27 men undergoing treatment with: 1) surveillance; 2) 1 to 2 cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (low-intensity cisplatin); or 3) 3 to 4 cycles of BEP (high-intensity cisplatin). Endothelial function (percentage flow-mediated dilatation) and cardiovascular biomarkers were assessed at 6 visits over 9 months. Cohort 2 consisted of 26 men previously treated 1 to 7 years ago with surveillance or 3 to 4 cycles BEP. Vasomotor and fibrinolytic responses to bradykinin, acetylcholine, and sodium nitroprusside were evaluated using forearm venous occlusion plethysmography.ResultsIn cohort 1, the percentage flow-mediated dilatation decreased 24 h after the first cisplatin dose in patients managed with 3 to 4 cycles BEP (10.9 ± 0.9 vs. 16.7 ± 1.6; p < 0.01) but was unchanged from baseline thereafter. Six weeks after starting 3 to 4 cycles BEP, there were increased serum cholesterol levels (7.2 ± 0.5 mmol/l vs. 5.5 ± 0.2 mmol/l; p = 0.01), hemoglobin A1c (41.8 ± 2.0 mmol/l vs. 35.5 ± 1.2 mmol/l; p < 0.001), von Willebrand factor antigen (62.4 ± 5.4 mmol/l vs. 45.2 ± 2.8 mmol/l; p = 0.048) and cystatin C (0.91 ± 0.07 mmol/l vs. 0.65 ± 0.09 mmol/l; p < 0.01). In cohort 2, intra-arterial bradykinin, acetylcholine, and sodium nitroprusside caused dose-dependent vasodilation (p < 0.0001). Vasomotor responses, endogenous fibrinolytic factor release, and cardiovascular biomarkers were not different in patients managed with 3 to 4 cycles of BEP versus surveillance.ConclusionsCisplatin-based chemotherapy induces acute and transient endothelial dysfunction, dyslipidemia, hyperglycemia, and nephrotoxicity in the early phases of treatment. Cardiovascular and renal protective strategies should target the early perichemotherapy period. (Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer [VECTOR], NCT03557177; Intermediate and Long Term Vascular Effects of Cisplatin in Patients With Testicular Cancer [INTELLECT], NCT03557164).

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Dataset Information

Vascular fingerprint tool to identify patients with testicular cancer treated with cisplatin-based chemotherapy at high risk of early cardiovascular events.

Background

Patients and methods

Results

Conclusions

Publications

Vascular fingerprint tool to identify patients with testicular cancer treated with cisplatin-based chemotherapy at high risk of early cardiovascular events.

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