Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Paal, K.
The impact of radiotherapy on cellular senescence
and chronic inflammation
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2024. pp. 120
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Langsenlehner Tanja
- Renner Wilfried
- Altmetrics:
- Abstract:
- Background: Ageing is a process leading to a gradual loss of function on cell, tissue and organ level. Age-related processes can be accelerated by a wide range of extrinsic and intrinsic stimuli. Cancer-directed therapies, including radiation therapy, can lead to the activation of chronic inflammatory processes, leading to the shrinkage of physiologic reserve, and therefore to the premature onset of age-related signs and symptoms. The assessment of the manifestations of ageing process can be conducted by the measurement of biomarkers of ageing in the blood, evaluations of the health status with the tools of comprehensive geriatric assessment as well as with the estimation of cellular senescence by the means of measurement of the telomere erosion on the chromosomes. Since the considerable percentage of cancer patients are elderly individuals, the investigation of the influence of cancer therapy on the ageing process gains more and more attention in science. Methods: A total of 314 patients treated with definitive radiation therapy (RT) for prostate cancer at the Department of Therapeutic Radiology and Oncology, Medical University of Graz were enrolled into our observational prospective study and underwent a comprehensive health status evaluation with the tools of geriatric assessment (GA) as well as the assessment of inflammatory parameters and measurement of leucocyte telomere length prior to the start of treatment and at two follow-ups 3 and 15 months after the completion of radiation. Blood sampling and measurement of biomarkers of ageing was also conducted at the end of RT course. The alterations of clinical, biochemical and molecular domains of ageing were evaluated with non-parametric tests. Additionally, correlations between pretherapeutic GA results and ageing-related biomarkers were analysed. Results: During the observation time, a significant decline was observed in patients’ social situation (p<0.001), mood state (p<0.001), nutritional status (p<0.001), and in instrumental activities of daily living (p=0.005). The ability to perform the basic activities of daily living and comorbidity burden did not change from the baseline to the second follow-up (p>0.05). Furthermore, we could observe an improvement in cognitive function (p=0.004) and patients’ mobility (p=0.032) between the pretherapeutic status and one of the reassessments. The results of biochemical markers of ageing showed a significant increase of fibrinogen (p<0.001), neutrophile to lymphocyte ratio (p<0.001), and platelet to lymphocyte ratio (p<0.001) between the baseline and at least one of the follow-up examinations. The results of the albumin and cholesterol levels in blood indicate a lowering of the metabolic reserve during the RT course (p<0.001) with a significant ability to recover after completed radiation therapy (p<0.001). Telomere length analysis showed a significant reduction in the relative telomere length 15 months after completion of radiotherapy compared to baseline (p=0.048) and the end of the radiotherapy series (p=0.040) Furthermore, several correlations between the clinical GA results and biochemical and molecular parameters of ageing could be detected. Conclusions: The alterations observed in our study cohort suggest a negative influence of curative radiation therapy on the majority of health components measured in our assessments. The prolonged elevation of the inflammatory parameters and the decrease of albumin and cholesterol levels during the longer observation period suggest that even small field RT can activate the chronic inflammatory process. The changes in relative telomere length imply that radiotherapy influences aging processes at the cellular level. In addition, the correlations detected between clinical and biochemical age-related parameters could be utilized in clinical practice for the identification of biologically older patients and for decision-making in cancer therapy.