Vascular aging in long-term survivors of testicular cancer more than 20 years after treatment with cisplatin-based chemotherapy.
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ABSTRACT: Background
Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. The objective was to assess vascular damage in very long-term TCS.Methods
TCS (treated with chemotherapy or orchiectomy only) and age-matched healthy controls were invited. Study assessment included vascular stiffness with ultrasound measurement of carotid-femoral pulse wave velocity (cf-PWV).Results
We included 127 TCS consisting of a chemotherapy group (70 patients) and an orchiectomy group (57 patients) along with 70 controls. Median follow-up was 28 years (range: 20-42). The cf-PWV (m/s) was higher in TCS than in controls (geometrical mean 8.05 (SD 1.23) vs. 7.60 (SD 1.21), p = 0.04). The cf-PWV was higher in the chemotherapy group than in the orchiectomy group (geometrical mean 8.39 (SD 1.22) vs. 7.61 (SD 1.21), p < 0.01). In the chemotherapy group cf-PWV increased more rapidly as a function of age compared to controls (regression coefficient b 7.59 × 10-3 vs. 4.04 × 10-3; p = 0.03).Conclusion
Very long-term TCS treated with cisplatin-based chemotherapy show increased vascular damage compatible with "accelerated vascular aging" and continue to be at risk for cardiovascular morbidity, thus supporting the need for intensive cardiovascular risk management.Clinical trial registration
The clinical trial registration number is NCT02572934.
SUBMITTER: Stelwagen J
PROVIDER: S-EPMC7686327 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundImpaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls.MethodsIn this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)-with a follow-up duration ≥ 20 years-and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs).ResultsWe included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20-42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score -0.85; 95% CI -1.39 to -0.33) compared to controls (mean 0.67; 95% CI -0.21 to 1.57, p < 0.01). In univariate analysis, the presence of hypogonadism (β -1.50, p < 0.01), high c-PWV (β -0.35, p = 0.09), and high AGEs (β -1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β -1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p < 0.01).ConclusionsLong-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment.Trial registrationNCT02572934.
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Project description:Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects. Other long-term adverse outcomes include neuro- and ototoxicity, pulmonary complications, nephrotoxicity, hypogonadism, infertility, and avascular necrosis. Future research efforts should focus on delineation of the genetic underpinning of these long-term toxicities to understand their biologic basis and etiopathogenetic pathways, with the goal of developing targeted prevention and intervention strategies to optimize risk-based care and minimize chronic morbidities. In the interim, health care providers should advise TCS to adhere to national guidelines for the management of cardiovascular disease risk factors, as well as to adopt behaviors consistent with a healthy lifestyle, including smoking cessation, a balanced diet, and a moderate to vigorous intensity exercise program. TCS should also follow national guidelines for cancer screening as currently applied to the general population.
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Project description:PurposeCancer survivors express anxiety that chemotherapy exposure may lead to transmissible genetic damage in posttreatment children. Preclinical models suggest that chemotherapy exposure may result in considerable genomic alterations in postexposure progeny. Epidemiologic studies have not demonstrated a significant increase in congenital abnormalities in posttreatment children of cancer survivors, but the inherited genome-wide effect of chemotherapy exposure in humans is unknown.Experimental designTwo testicular cancer survivors cured with chemotherapy who had children pre- and postexposure without sperm banking were identified. Familial germline whole genome sequencing (WGS) was performed for these families, and analytic methods were utilized to identify de novo alterations, including mutations, recombinations, and structural rearrangements in the pre- and postexposure offspring.ResultsNo increase in de novo germline mutations in postexposure children compared with their preexposure siblings was found. Furthermore, there were no increased short insertion/deletions, recombination frequency, or structural rearrangements in these postexposure children.ConclusionsIn two families of male cancer survivors, there was no transmissible genomic impact of significant mutagenic exposure in postexposure children. This study may provide possible reassuring evidence for patients undergoing chemotherapy who are unable to have pretreatment sperm cryopreservation. Expanded cohorts that utilize WGS to identify environmental exposure effects on the inherited genome may inform the generalizability of these results. Clin Cancer Res; 22(9); 2183-9. ©2015 AACR.
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Project description:BackgroundPatients 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 methodsWe 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.ResultsA 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).ConclusionsThe 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.
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Project description:BACKGROUND:Treatment for cancer may lead to development of cognitive difficulties in cancer survivors. This study aimed to evaluate long-term cognitive functioning (CogF) in germ-cell tumor (GCT) survivors. SUBJECTS, MATERIALS, AND METHODS:GCT survivors (n = 155) from the National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function at a median of 10 years of follow-up (range: 5-32). The study group consisted of survivors receiving a cisplatin-based chemotherapy, radiotherapy to the retroperitoneal lymph nodes, or both, whereas the control group included survivors treated with orchiectomy only. RESULTS:Of the total survivors, 138 received treatment beyond orchiectomy and 17 controls had orchiectomy alone. Any treatment resulted in significantly greater cognitive difficulties on the overall cognitive function score. Treatment with radiotherapy was associated with cognitive declines in overall cognitive functioning and in subscales for perceived cognitive impairment and cognitive impairment perceived by others (both p < .05). The burden of chemotherapy plus radiotherapy or radiotherapy versus controls resulted in the impairment in all cognitive functioning domains (all p < .05). Overall long-term cognitive impairment was independent of age in the multivariable analysis. CONCLUSION:This prospective study shows that GCT survivors suffer from a long-term CogF impairment. These results may help guide clinicians' decisions in treatment and follow-up of GCTs. IMPLICATIONS FOR PRACTICE:In this study, long-term survivors of germ-cell tumors have reported cognitive impairment after curative treatment with radiotherapy and chemotherapy compared with controls who had treatment with orchiectomy only. These data provide an argument against the use of adjuvant radiotherapy for stage I seminoma. Unnecessary overtreatment with chemotherapy and additional radiotherapy after chemotherapy should be avoided.
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