AbstractThe capacity to diagnose and stage prostate cancer (PC) is restricted and generally based on pre-treatment assessments such as the prostate-specific antigen (PSA), TNM stages, and the pathologic Gleason score. However, existing pre-treatment tools cannot be used to predict acute RT-induced toxicity. Therefore, new protein biomarkers are required in RT oncology to improve decision-making, treatment and therapy monitoring for PC patients.
This prospective study aimed to assess the magnitude and frequency (increase/decrease) of changes in cytokine expression in patients receiving androgen deprivation therapy (ADT) and intensity-modulated radiotherapy (IMRT) for PC and to link these changes to clinicopathological characteristics and acute RT-induced toxicity. Principal findings include the following:
Firstly, IHC expression levels of TNF-α, TGF-β1 and IL-6 were significantly reduced with increased GSs and a significant correlation was only found between TNF-α expression levels and GSs.
Secondly, a statistically significant correlation was found between the amount of pre-RT plasma levels and the staining intensity of the corresponding prostatic needle-biopsy specimens.
Thirdly, profibrotic cytokine TGF-β1 levels were elevated at the end of RT over baseline. In addition, IL-6 increased after 3 months completion of RT when compared with baseline and end of RT blood plasma samples.
Fourthly, elevated levels of TNF-α and IL-6 were associated with the higher probability of acute genitourinary and gastrointestinal toxicity.
Finally, the levels of profibrotic TGF-β1 decreased as the severity of genitourinary and gastrointestinal increased.
This dissertation provides the evidence of the overexpression of cytokines in prostatic needle-biopsy specimens and influence of androgen deprivation therapy (ADT) and radiotherapy (RT) on the changes in cytokine levels in blood plasma before and after curative treatments. In addition, our study also provides the evidence of the association of cytokines levels in blood and acute RT-induced toxicity.
|Date of Award||2018|
|Supervisor||Sohal Sukhwinder Singh (Supervisor)|