Brachytherapy, Hypofractionation, Localized Prostate Carcinoma, Prostate Cancer, Radiotherapy, Radiotherapy Side Effect
Conditions
Keywords
hypo fractionation, brachytherapy, Ultra Hypo fractionation
Brief summary
Phase 1-2 study, comparing ultra-hypofractionnated (UH) to a moderately hypofractionnated (MH) radiation therapy, with image guided HDR prostate brachytherapy. Using iso-equivalent doses, a non-inferiority analysis will be done in order to prove UH non-inferior to MH, toxicity wise. Acceptability, tolerability, acute and late toxicity will be reported. MRI visible dominant intra-prostatic lesion will be outlines and variability between radiation oncologists and radiologists will be reported. As secondary objective, biochemical and clinical failure free survival will be reported at 5 & 10 years.
Detailed description
Phase 1 : consists in a feasibility study (First 28 patients). Phase 2 : monocentric prospective comparative cohort study. Recruitment : * Centre intégré de cancérologie du CHU de Québec-Université Laval. * Recruitment period: December 2015 to June 2023 Brachytherapy : * Implantation under general or spinal anesthesia * Foley catheter insertion in bladder. * TRUS prostate localisation. * Prostate volume measurement. * Gold fiducial markers (3) insertion. * Prostate brachytherapy catheters (14 à 21) insertion. * Cystoscopy for bladder and urethra integrity control. * Re-insertion of foley catheter after cystoscopy. Planning imaging: TRUS or CT scan (has needed). Structures delineation by radiation oncologist (brachytherapist). * Prostate * Seminale vesicles * Rectum * Colon sigmoïde * Bladder * Urethra * Penile bulb Dosimetric optimisation * Oncentra Prostate v. 4.2.2 d'Elekta brachytherapy (Veenendaal, The Netherlands) * Oncentra Brachy version 4.6 (if under CT scan). Treatment (brachytherapy dose delivery). * 15 Gy in one fraction * Direct interstitial dose monitoring (20 patients or more). Fiber-optic dosimeter inserted in prostate brachytherpy catheter for live dose delivery mesurements. Foley ablation under full bladder, same day or day after therapy. Radiotherapy: * Via IMRT, VMAT or SBRT technics. * Dose : 25 Gy in 5 fractions administered over a 7 days period. 2 to 3 fractions separated by 2 days, weekend break. * PTV includes prostate and the first centimeter of seminal vesicle. Simulation * one week post brachytherapy * standard has described in the department procedure manual. * maximal CT scan slice thickness : 2-3mm. * uretro-graphy done to identify urogenital sphincter. Multiparametric MRI * If no counter-indication and available, * a T2 tridimensional sequence for prostate delineation * slice thickness : 1 mm. * a diffusion weighted sequence will be done. * a DTI with tractography can be done optionally. * contrast media (gadolinium) is optional. Physique * Linac energy (between 6 MV to 18 MV). * ARC therapy technique will be used * planification softwares: Éclipse, Pinnacle or Raystation. * Portal (kV-kV) imagery will be used for marker match. * CBCT will be done at each fraction delivered. Clinical and dosimetric data will be collected prior treatment. Primary objectives : * Toxicity analysis will be quantitatively evaluated using CTCAE (v5) at 1, 2 and 5 years post-therapy, and has needed at FU visits. Kaplan-Meier statistical analysis will be used to report toxicity evolution through time. * median IPSS scores will be reported at 3, 6, 12 months and yearly (1, 2, 3, 4 et 5) post-therapy. IPSS median time to baseline return will be calculated. * IPSS urinary scores, sexual function (SHIM) and GI toxicity (CTCAE-v5) and quality of life questionnaires ( EPIC-26) will be given at 3, 6 months and yearly thereafter (1, 2, 3, 4 et 5) post-treatment. Secondary objectives : Biochemical disease-free survival has per Phoenix definition (by American Society of Radiation Oncology - ASTRO) recommendation will be reported using Kaplan-Meier analysis.
Interventions
RADIATIONgrade and compare reported side effects between groups
Compare experimental ultra hypo fractionation (25 Gy in 5 daily fractions administered starting mid week and ending mid following week) to our standard fractionation (either 37,5 Gy given in 15 daily fractions, or 36 Gy in 12 daily fractions). * Toxicity analysis will be quantitatively evaluated using CTCAE (v5) at 1, 2 and 5 years post-therapy, and has needed at FU visits. Kaplan-Meier statistical analysis will be used to report toxicity evolution through time. * median IPSS scores will be reported at 3, 6, 12 months and yearly (1, 2, 3, 4 et 5) post-therapy. IPSS median time to baseline return will be calculated. * IPSS urinary scores, sexual function (SHIM) and GI toxicity (CTCAE-v5) and quality of life questionnaires ( EPIC-26) will be given at 3, 6 months and yearly thereafter (1, 2, 3, 4 et 5) post-treatment.
Sponsors
CHU de Quebec-Universite Laval
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective comparative cohort study with non inferiority analysis UH-IMRT combined to 15 Gy HDR Brachytherapy will considerably reduce the treatment fraction delivered while maintaining b-DFS and Side-effects at comparable levels to our actual reported prostate cancer patient population, without lymph nodes involvement (risk being less than 15%). We believe that this therapeutic regime will show to be non-inferior to our actual standard therapeutic regime
Eligibility
Sex/Gender
MALE
Age
18 Years to 95 Years
Healthy volunteers
Yes
Inclusion criteria
* Biopsy proven Prostate adenocarcinoma * Stage T1c, T2 (Annex 2) * Stage Nx or N0 * Stage Mx or M0 * PSA \< 20ng/ml * Gleason Score 6 or 7 * Having the ability to sing a written consent
Exclusion criteria
* Age \< 18ans * Clinical Stage T3 or T4 * Stage N1 * Stage M1 * PSA \> 20 * Gleason Score 8 to 10 * IPSS Score \> 20 alpha-blocking medication. * Prior pelvic radiotherapy. * History of active collagenosis (Lupus, Sclerodermia, Dermatomyosis) * Past history of Inflammatory Bowell Disease * Bilateral hip prosthesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| sexual function analysis (SHIM) | baseline, prior treatment | median SHIM scores will be reported at baseline prior treatment |
| quality of life questionnaires analysis (EPIC26) | baseline, prior treatment | median EPIC26 scores will be reported post-therapy and compare between arms at baseline, prior treatment |
| GU toxicity analysis (CTCAE) | at baseline, prior treatment | quantitatively evaluated using CTCAE (v5) and compare between arms |
| GI toxicity analysis (CTCAE) | at baseline, prior treatment | quantitatively evaluated using CTCAE (v5) and compare between arms |
| urinary toxicity analysis (IPSS) | at baseline, prior treatment | median IPSS scores will be reported post-therapy and compare between arms at baseline, prior treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical outcomes | at 5 years | Biochemical disease-free survival has per Phoenix definition (by American Society of Radiation Oncology - ASTRO) will be reported using Kaplan-Meier analysis, as well for disease free survival, metastasis free survival and overall survival. |
Countries
Canada
Contacts
Primary ContactAndre-Guy Martin
Backup ContactJosee Allard
Outcome results
None listed