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Vascular damage and pulmonary function in very long-term survivors of testicular cancer (TC) treated with cisplatin-based chemotherapy (CT)

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Presenters

Johannes Stelwagen

Citation

Annals of Oncology (2018) 29 (suppl_8): viii303-viii331. 10.1093/annonc/mdy283

Authors

J. Stelwagen1, S. Lubberts1, L.C. Steggink1, G. Steursma1, L.M. Kruyt1, J.W. Donkerbroek1, A.M. van Roon2, A.I. van Gessel2, S.C. van de Zande2, C. Meijer1, J.B. Wempe3, C.H. Gräfin zu Eulenburg4, J. Nuver1, A.M.E. Walenkamp1, J.D. Lefrandt2, J.A. Gietema1

Author affiliations

  • 1 Medical Oncology, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 2 Internal Medicine, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 3 Pulmonology, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 4 Epidemiology, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
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Resources

Background

Late effects are a source of long term cardiovascular and pulmonary morbidity in testicular cancer (TC) survivors. The objective was to assess vascular damage and pulmonary function in TC survivors more than 20 years after cisplatin-bleomycin combination CT and compare this to age-matched patients treated for TC with surgery only (SU) as well as healthy male controls (CO).

Methods

Aortic stiffness was measured by the gold standard of aortic pulse-wave velocity (aPWV) from the carotid to femoral artery. aPWV is considered an accurate predictor of cardiovascular risk. Additional blood markers for vascular damage were assessed, including factor VIII, v-WF and fibrinogen. Pulmonary function including Diffusion Capacity Carbon Monoxide (DLCO) was assessed according to international guidelines using spirometry, body-plethysmography and the single breath-holding method parameters.

Results

After a mean follow-up duration of 28 years (range: 20-42), aPWV and DLCO was assessed in 118 TC survivors (63 CT patients and 55 SU patients) and 56 controls. aPWV (m/s) was higher in the CT group as compared to the SU and CO group (geometric mean 8.49 vs 7.69 and 7.64 respectively, P = 0.005). DLCO (% predicted) was significantly reduced in CT patients compared to SU patients (87% vs 94%, P = 0.02).A significant reduction in DLCO (defined as < 80% of predicted) occurred in 27% and 13% for CT and SU patients, respectively (X2; P = 0.055). In the CT patient group, aPWV and DLCO were associated (r = 0.3, P = 0.03). Furthermore, in the CT patient group, DLCO and endothelial activation markers were associated (vWF r=-0.30, P = 0.02; F-VIII r=-0.31, P = 0.01; fibrinogen r=-0.27, P = 0.03).

Conclusions

TC survivors treated with cisplatin-bleomycin combination chemotherapy have an increased aortic stiffness and reduced DLCO more than 20 years after treatment. This implicates an increased risk of cardiovascular morbidity and impaired pulmonary function. Association between markers for vascular damage and reduced DLCO suggests a role of vascular damage in the etiology of pulmonary dysfunction for TC survivors.

Clinical trial identification

NCT02572934.

Legal entity responsible for the study

University Medical Center Groningen, The Netherlands (PI: Prof. Dr. J.A. Gietema).

Funding

Dutch Cancer Society, Grant no. RUG2011-5267.

Editorial Acknowledgement

Disclosure

J.A. Gietema: Research funding to institute: Roche, Abbvie, Siemens. All other authors have declared no conflicts of interest.

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