Prostate Adenocarcinoma, Prostate Cancer, Prostatic Neoplasms
Conditions
Keywords
Radiotherapy, Microbiome, Metabolome
Brief summary
Radiotherapy (RT) of the abdomen and/or pelvis is known to cause acute and late gastrointestinal (GI) toxicities. While radiation dose and volume are known risk factors for developing such side effects, recent evidence suggests patterns of disturbance in the composition of the GI microbiota - so called dysbiosis - may also promote the host's susceptibility to GI toxicities through impaired intestinal barrier function and inflammation. The IMPRINT-study aims to expand the current knowledge on the role of intestinal bacteria and their metabolites involved in the pathophysiology of radiation-induced GI toxicities by longitudinally examining the microbiota composition (feces), the associated metabolome (blood, feces and urine) and bacterial extracellular vesicles (BEVs) (blood and feces).
Detailed description
The IMPRINT-study is a prospective biomarker study assessing the impact of different treatment field sizes and associated radiation doses on the patient's microbiome and metabolome, whereby the link with radiation-induced GI toxicities will be emphasized. Blood, urine and fecal samples will be longitudinally collected at 4 different time points: (1) shortly before, (2) during and (3) shortly after RT treatment, as well as (4) one-month post-RT. To our knowledge, this is the first clinical research project relating the impact of multiple radiation parameters on fecal-, urine- and blood-based biomarkers to risk of GI toxicities in a homogeneously defined study population.
Interventions
OTHERCollection of human biofluids
Feces, blood and urine: (1) shortly before, (2) during and (3) shortly after RT treatment, as well as (4) one-month post-RT
OTHERPatient reported outcome measures
EORTC QLQ-C30, PR25: (1) shortly before and (2) shortly after RT treatment, as well as (3) one-month post-RT
Sponsors
University Hospital, Ghent
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven (initial) adenocarcinoma of the prostate * Localized (confined to primary site) and/or regional (spread to regional pelvic lymph nodes) disease stage at diagnosis * Age ≥ 18 years * RT is an integral part of the treatment - primary, adjuvant or salvage * WHO performance status 0-2 * Administration of androgen deprivation therapy (ADT) before RT * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * Signed informed consent form (ICF) according to ICH/GCP and national/regional regulations
Exclusion criteria
* Other primary tumor (except for non-melanoma skin cancer) diagnosed \< 5 years before enrollment * Diagnosis of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) * Administration of systemic therapy during RT other that ADT * Subjected to antibiotic treatment or medically imposed dietary restrictions \< 1 month prior to enrollment * Body mass index (BMI) \> 35 * Administration of pelvic RT \< 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microbiome profiles as assessed by fecal samples | Up to 3.5 months after inclusion | Characterization of dynamic changes in the intestinal microbiota composition using 16S rRNA sequencing technology |
| Metabolome profiles as assessed by fecal, blood and urine samples | Up to 3.5 months after inclusion | Characterization of dynamic changes in the concentration of all small molecules (metabolites) in feces, blood and urine using ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of GI and Genitourinary (GU) toxicities | Up to 3.5 months after inclusion | GI and GU toxicities as per Common Terminology for Adverse Events (CTCAE) v4.0 |
| Concentration of BEVs in fecal and blood samples | Up to 3.5 months after inclusion | BEVs in fecal and blood samples will be separated and analyzed through the orthogonal implementation of ultrafiltration, size-exclusion chromatography (SEC) and density-gradient centrifugation, followed by biochemical characterization |
| Patient reported QOL as per EORTC-QLQ PR25 | Up to 3.5 months after inclusion | Validated questionnaire assessing the health-related QOL of prostate cancer patients |
| Patient reported QOL as per EORTC-QLQ C30 | Up to 3.5 months after inclusion | Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients |
| Discovery of potential predictive biomarkers for the development of RT-induced GI toxicities | Up to 3.5 months after inclusion | The identified microbiota and metabolite signatures will be investigated for association with incidence and severity of GI toxicities |
Countries
Belgium
Outcome results
None listed