Vascular aging in long-term survivors of testicular cancer more than 20 years after treatment with cisplatin-based chemotherapy

Stelwagen, J.; Lubberts, Sjoukje; Steggink, Lars C; Steursma, Gerrie; Kruyt, Lara M.; Donkerbroek, Jan Willem; Roon, Arie M. van; Gessel, Anne I. van; Zande, Saskia Corine van de; Meijer, Coby; Eulenburg, Christine; Oosting, Sjoukje F.; Nuver, Janine; Walenkamp, Annemiek; Jong, Igle J. de; Lefrandt, Joop D.; Gietema, Jourik A.

doi:10.1038/s41416-020-01049-3

Cited by 21 publications

(11 citation statements)

References 36 publications

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“…Other late risks following BEP include the development of hypertension, hyperlipidemia, diabetes mellitus, and metabolic syndrome [ 1 , 2 ]. Late adverse vascular effects of platinum drugs have been attributed to platinum-related disruptions of vascular endothelial cells [ 3 ] resulting in a proinflammatory state, leading to atherosclerosis (occurring months to years after exposure), and “accelerated vascular aging” [ 5 ].…”

Section: Short Communicationmentioning

confidence: 99%

Cisplatin, environmental metals, and cardiovascular disease: an urgent need to understand underlying mechanisms

et al. 2021

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Significantly increased risks of cardiovascular disease occur in testicular cancer survivors given cisplatin-based chemotherapy. The postulated mechanism of platinum-based chemotherapy’s vascular toxicity has been thought secondary to its different early- and late- effects on vascular injury, endothelial dysfunction, and induction of a hypercoagulable state. We highlight for the first time the similarities between platinum-associated vascular adverse events and the vascular toxicity associated with other xenobiotic-metal contaminants. The vascular toxicity seen in large epidemiologic studies of testicular cancer survivors may in part be similar and mechanistically linked to the risk seen in environmental heavy metal contaminants linked to cardiovascular disease. Future research should be directed to better understand the magnitude of the adverse cardiovascular effects of platinum and to elucidate the underlying mechanisms of action.

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Section: Short Communicationmentioning

confidence: 99%

Cisplatin, environmental metals, and cardiovascular disease: an urgent need to understand underlying mechanisms

et al. 2021

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“…TC survivors have an enhanced risk of developing early cardiovascular disease [45]. This "accelerated vascular aging" could be a factor in the decreased cognitive performance shown in our study.…”

Section: Discussionmentioning

confidence: 54%

Cognitive Impairment in Long-Term Survivors of Testicular Cancer More Than 20 Years after Treatment

Stelwagen

Meuleman

Lubberts

et al. 2021

Cancers

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Background: Impaired 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. Methods: In 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). Results: We 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). Conclusions: Long-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 Registration: NCT02572934.

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“…In addition to increased risk of metabolic syndrome in chemotherapy patients, there is mounting evidence of early or accelerated vascular aging, leading to increased arterial stiffness, thought to be secondary to direct cisplatin-related vascular damage. 58 At present, there is no clear management strategy for decreasing the risk of chemotherapy-induced early vascular aging. 58 Metabolic syndrome occurs in the general population and is a major risk factor for CVD.…”

Section: Management Recommendationsmentioning

confidence: 99%

Testicular cancer survivorship: Long-term toxicity and management

Shrem

Wood

Hamilton

et al. 2022

CUAJ

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Vascular aging in long-term survivors of testicular cancer more than 20 years after treatment with cisplatin-based chemotherapy

Cited by 21 publications

References 36 publications

Cisplatin, environmental metals, and cardiovascular disease: an urgent need to understand underlying mechanisms

Cisplatin, environmental metals, and cardiovascular disease: an urgent need to understand underlying mechanisms

Cognitive Impairment in Long-Term Survivors of Testicular Cancer More Than 20 Years after Treatment

Testicular cancer survivorship: Long-term toxicity and management

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