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Longitudinal Evaluation of Intestinal, Haematological and Urinary Toxicity From Pelvic Irradiation for Prostate Cancer

ABSTRACT: The prophylactic irradiation of pelvic lymph-nodes by means of Whole-Pelvis Radiotherapy (WPRT) in the treatment of prostate cancer (PCa) is aimed at the timely eradication of microscopic lymph-nodal metastases. Nevertheless, even though delivered by means of modern Intensity-Modulated Radiotherapy (IMRT) techniques, WPRT may result in intestinal, hematologic and urinary toxicity (IT, HT, UT, respectively) severely affecting patients’ daily health-related quality-of-life (HRQoL) within the so-called and inadequately investigated Pelvic Radiation Disease. The aim of this study is to develop sophisticated predictive models of IMRT-WPRT induced patient-reported HT, IT and UT in PCa. The possible correlation between several clinical factors and radiation doses received by various pelvic structures (i.e. pelvic bones subvolumes, intestinal loops, sigmoid, rectum and bladder) and risk and severity of patient-reported IT, UT and HT will be analyzed and robust multi-variable models will be developed and internally validated. A secondary end-point will be the identification of specific symptoms affecting patients’ HRQoL during irradiation and in the long term, overall and in different therapeutic settings (radical, adjuvant and salvage). Lastly, possible correlation between HT and UT/IT will be investigated.

DISEASE(S): Prostatic Neoplasms,Prostate Cancer

PROVIDER: 2217512 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Prostate cancer (PCa) is the second most prevalent malignancy in Western countries and the fifth leading cause of cancer-related death in men. The risk factors for PCa include obesity, age, and family history. Visceral fat has been linked to PCa risk, which has prompted researchers to investigate the influence of body composition and fat distribution on PCa prognosis. This study investigated the correlation between the composition of pelvic adipose tissue (PAT) and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, we prepared a periprostatic adipose tissue (PPAT)-conditioned medium (CM) to determine the influence of the PPAT secretome on the pathophysiology of PCa. This study included 60 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, and magnetic resonance imaging scans were analyzed, and body compositions were calculated to identify the correlations between adipose tissue volume and clinical PCa aggressiveness. CM was prepared using PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its influence was investigated using the PCa cell lines C4-2 and LNCaP and the prostate epithelial cell line PZ-HPV-7. Cell proliferation assays and RNA sequencing were performed. The initial prostate-specific antigen level was significantly correlated with pelvic and perirectal adipose tissue volumes. PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cells proliferated was significantly slower when cultured in PPAT-CM compared with when cultured in control- and PVAT-CM. RNA sequencing revealed that immune responses and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells. The cytokines or other secreted factors in PPAT-CM induced PCa cell apoptosis. This in vitro study revealed that the PPAT secretome inhibits PCa cells proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

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Longitudinal Evaluation of Intestinal, Haematological and Urinary Toxicity From Pelvic Irradiation for Prostate Cancer

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