Prostate Cancer
Conditions
Keywords
Stereotactic Body Radiotherapy, Late Toxicity, RILA, Predictive Biomarker, Prostate cancer
Brief summary
This monocentric interventional study investigates whether the Radio-induced Lymphocyte Apoptosis (RILA) assay can predict the occurrence of late radiation-induced toxicities in patients with localized prostate cancer treated with stereotactic body radiotherapy (SBRT). Eligible patients will undergo a peripheral blood sample collection for the RILA test prior to SBRT. Toxicities will be assessed using CTCAE v5.0 criteria, and quality of life will be evaluated with EORTC QLQ-PR25, QLQ-C30, and IPSS questionnaires over a 60-month follow-up. The results aim to optimize patient selection for SBRT and reduce the risk of severe late side effects.
Detailed description
PROSTERA is a prospective, single-arm, monocentric interventional study (RIPH-2) designed to evaluate the prognostic performance of the Radio-induced Lymphocyte Apoptosis (RILA) assay to predict late radiation-induced toxicities in patients with localized prostate cancer treated with stereotactic body radiotherapy (SBRT). The primary objective is to determine whether pre-treatment RILA (percentage of apoptotic T-lymphocytes measured ex-vivo after controlled irradiation) is predictive of clinically meaningful late toxicities graded ≥2 according to CTCAE v5.0 within 24 months after SBRT. Secondary objectives include PSA kinetics, patient-reported outcomes (EORTC QLQ-PR25, QLQ-C30 and IPSS), dosimetric correlations, and estimation of diagnostic performance metrics (AUC, sensitivity, specificity) of the RILA assay. A single peripheral blood sample (2 mL) is collected at the time of CT simulation (inclusion visit). Samples are transported to the designated laboratory (LIRS/RunResearch) and processed according to the RILA SOP: cells are placed in culture (RPMI 1640 + 20% FBS, dilution 1:10) within 4 hours of collection, incubated 16-24 hours, then irradiated ex-vivo (8 Gy; conformational irradiation using institutional accelerator) and incubated for an additional 48 hours. After post-irradiation incubation cells are stained for CD4/CD8 and propidium iodide and analysed by flow cytometry (FACS) on 10,000 events in triplicate to derive the percentage of apoptotic CD4+ and CD8+ T-cells. All assay timings and plate/aliquot identifiers are recorded in laboratory logs. The collected sample is entirely consumed for the assay (no sample retention). Eligible participants are adult males with localized prostate adenocarcinoma meeting the protocol inclusion criteria (e.g. clinical stage T1-T2, Gleason score 6-7, PSA \<15 ng/mL as per protocol), able to provide written informed consent and compliant with follow-up procedures. Key exclusions include prior pelvic radiotherapy, metastatic disease, inability to consent, and other criteria listed in the protocol. Enrollment will be consecutive to limit selection bias. All participants receive SBRT delivered according to institutional conformational technique (protocol-specified dose constraints and organ-at-risk delineation per RTOG recommendations; typical stereotactic schedule described in the protocol). Imaging data (centering CT and any low-dose CT), treatment plans and dose-volume histograms (DVH) will be collected and stored in the electronic CRF for dose-toxicity correlation analyses. Safety and patient-reported outcomes will be recorded during routine follow-up visits at baseline (pre-SBRT) and at 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months post-radiotherapy; CTCAE v5.0 will be used for toxicity grading and the EORTC QLQ-PR25, QLQ-C30 and IPSS questionnaires for quality-of-life and urinary symptom assessment. PSA will be measured at the same scheduled timepoints. No additional study-specific clinic visits are required beyond standard care. The planned sample size is 220 subjects (calculated to achieve the desired precision for the RILA AUC estimate; \ 166 evaluable subjects minimally required), with an anticipated inclusion period of 24 months and maximum individual follow-up of 61 months (total study duration ≈ 88 months). Data will be recorded in a pseudonymized electronic CRF and source documents will remain available in patient medical records. The study will be conducted under the applicable ethical and regulatory framework (CPP approval, MR-001, GDPR).
Interventions
DIAGNOSTIC_TESTRadio-induced Lymphocyte Apoptosis (RILA) Assay
peripheral blood sample processed via the RILA assay to quantify apoptotic CD8+/CD4+ T cells following ex vivo irradiation.
RADIATIONStereotactic body radiotherapy (SBRT)
SBRT delivered to the prostate with image guidance, respecting dose constraints for organs at risk;
Sponsors
Clinique Sainte Clotilde
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male, aged 60 years or older, presenting with localized prostate cancer of low or intermediate risk (T1-T2 stage, Gleason score 6-7, and PSA \<15 ng/mL) without metastatic disease, and for whom radiotherapy is indicated. * Patient affiliated with, or beneficiary of, the French national health insurance system. * French-speaking patient. * Patient who has been informed about the study and has provided written informed consent.
Exclusion criteria
* Patient unable to read, write, or understand French. * Vulnerable patient as defined in Article L1121-6 of the French Public Health Code. * Adult under legal guardianship, curatorship, or judicial protection. * Patient unable to personally provide informed consent as per Article L1121-8 of the French Public Health Code, or adult protected by law. * Patient already enrolled in an interventional study that could influence the outcomes of the present study. * Patient with a history of prostate and/or digestive surgery. * Refusal to sign the written informed consent at inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of one or more late radiation-induced complications | 24 months post-stereotactic radiotherapy | Number of participants presenting one or more late radiation-induced complications, assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical and biological variables of patients | At baseline and during follow-up (up to 60 months post-radiotherapy) | Evaluation of clinical and biological variables (e.g., blood counts, PSA, comorbidities) collected during follow-up. Unit of Measure: Values according to each variable (e.g., PSA ng/mL, blood counts G/L, yes/no for comorbidities) |
| Mortality rate of T-CD8+/-CD4+ lymphocytes | After in vitro culture and irradiation at 8 Gy | Percentage of T-CD8+/-CD4+ lymphocytes mortality measured by flow cytometry after in vitro culture of blood samples and irradiation at 8 Gy. |
| Quality of life - EORTC QLQ-C30 | Baseline, 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months post-radiotherapy | Scores reported according to the validated scale (0-100). Higher scores = worse symptoms, better functioning for functional/global health. Unit of Measure: Score (0-100) |
| Urinary symptoms - International Prostate Symptom Score (IPSS) | Baseline, 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months post-radiotherapy | Validated 0-35 scale, where higher scores = worse urinary symptoms. Unit of Measure: Score (0-35) |
| Treatment tolerance - Number of participants with adverse events | Baseline, 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months post-radiotherapy | Graded according to CTCAE v5.0 (Grades 1-5). |
| Quality of life - EORTC QLQ-PR25 | Baseline, 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months post-radiotherapy | Scores reported according to the validated scale (0-100). Higher scores = worse symptoms/problems, better functioning for functional scales. Score (0-100) |
Contacts
CONTACTManon LEPRINCE, Clinical Research Associate
PRINCIPAL_INVESTIGATORMickael DR Begue, Doctor
Clinique Sainte Clotilde
Outcome results
None listed