Long term pulmonary function after treatment for testicular cancer

Stelwagen, J. (2017) Long term pulmonary function after treatment for testicular cancer. thesis, Medicine.

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Abstract

BACKGROUNDS: Following the introduction of platinum-based chemotherapy in the late 1970s, testicular cancer (TC) survival rates increased exceedingly. These survival rates in combination with an increasing incidence led to a rise in the number of TC survivors and therefore treatment-related adverse effects emerged as an important concern. Vascular damage has been shown to play a role in the development of adverse effects and might also be of importance in long term pulmonary function. Prevalence of pulmonary function disorders more than 20 years after treatment have never been assessed and its pathophysiological mechanisms are still poorly understood. AIMS: (i) To describe pulmonary function in very long-term TC survivors and compare prevalence of pulmonary function disorders in relation to TC treatment. (ii) To investigate correlation between markers for vascular damage and pulmonary function, (iii) to investigate correlation between renal function and pulmonary function. METHODS: We performed a cross-sectional cohort study in which patients treated with orchiectomy only or chemotherapy for TC more than 20 years ago (1977–1996) and age-matched controls were invited for a single study visit. Pulmonary function was assessed in TC survivors (spirometry, bodyplethysmography and diffusion capacity for carbon monoxide (DLCO)). Reference values of the general population were used from literature to calculate Z-scores. Furthermore, markers for vascular damage (i.e. biochemical markers, advanced glycation end-products, intima media thickness and pulse wave velocity) and renal function (24-hour urine collection) were assessed and correlation between these markers and pulmonary function was investigated. Disease- and treatment details and –in a part of the patients- pulmonary function tests before start of TC treatment were available from medical history. Cardiovascular risk factors (i.e. BMI, hypertension and history of smoking) were assessed during the study visit. RESULTS: Pulmonary function was assessed in 88 TC survivors. TC survivors did not show an increased incidence in restrictive lung disease (3%), but prevalence of reduced diffusion capacity (DLCO) was significantly higher in patients treated with chemotherapy (21%) compared to treatment with orchiectomy only (4%) (OR 6.1, P = 0.04). There was a significant decrease in DLCO during treatment but this showed a complete recovery to pre-chemotherapy DLCO after a median follow-up of 27 years. Prevalence of pulmonary function disorders at time of follow-up was positively correlated to the vascular damage markers t-PA (OR 1.2 (95% CI: 1.07-1.41)) and fibrinogen (OR 2.8 (95% CI: 1.19-6.80)). Furthermore advanced glycation end products (AGEs) were also correlated to the occurrence of reduced DLCO (OR 5.8 (95% CI: 1.1-30.4)). Other vascular damage markers and renal function did not correlate with pulmonary function. CONCLUSION: After successful completion of the treatment, TC survivors who were treated with chemotherapy had a higher risk developing decreased DLCO which was also correlated to some biochemical markers for vascular damage and to AGEs. This might be due to vascular damage related to the administration of cisplatin. The prevalence found of restrictive lung disease show discrepancy with literature and might suggest continuation of recovery in pulmonary function. More patients who received orchiectomy only are needed in order to reliably investigate the difference between pulmonary function dependant on treatment strategy.

Item Type:	Thesis (Thesis)
Supervisor name:	Supervisors: and Gietema, Prof. Dr. J.A. and Lubberts, drs. S. and Institution: University Medical Centre Groningen and Department: Medical Oncology and Research line: Testicular Cancer
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:51
Last Modified:	25 Jun 2020 10:51
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1234

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