Ultra Hypofractionnated Radiotherapy With HDR Brachytherapy Boost.

Официальное название

ULTRA-HYPO Fractionated (UHF) Compared to Moderate-HYPO Fractionated (MHF) Prostate IGRT With HDR Brachytherapy BOOST : A Phase 1-2 Study.

Обзор

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.

Подробное описание

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.

Вмешательства

• Лучевая терапия grade 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 rep

Первичные конечные точки

• GU toxicity analysis (CTCAE) [Срок оценки: at baseline, prior treatment]
• GU toxicity analysis (CTCAE) [Срок оценки: at 3 months post-therapy]
• GU toxicity analysis (CTCAE) [Срок оценки: at 6 months post-therapy]
• GU toxicity analysis (CTCAE) [Срок оценки: at 1 year post-therapy]
• GU toxicity analysis (CTCAE) [Срок оценки: at 2 years post-therapy]
• GU toxicity analysis (CTCAE) [Срок оценки: at 3 years post-therapy]
• GU toxicity analysis (CTCAE) [Срок оценки: at 4 years post-therapy]
• GU toxicity analysis (CTCAE) [Срок оценки: at 5 years post-therapy]
• GI toxicity analysis (CTCAE) [Срок оценки: at baseline, prior treatment]
• GI toxicity analysis (CTCAE) [Срок оценки: at 3 months post-therapy]

Вторичные конечные точки (2)

• Clinical outcomes [Срок оценки: at 5 years]
• Clinical outcomes [Срок оценки: at 10 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• CHUdeQuebec — Québec

Публикации

• Crook JM, Gomez-Iturriaga A, Wallace K, Ma C, Fung S, Alibhai S, Jewett M, Fleshner N. Comparison of health-related quality of life 5 years after SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial. J Clin Oncol. 2011 Feb 1;29(4):362-8. doi: 10.1200/JCO.2010.31.7305. Epub 2010 Dec 13. PMID 21149658
• Bachand F, Martin AG, Beaulieu L, Harel F, Vigneault E. An eight-year experience of HDR brachytherapy boost for localized prostate cancer: biopsy and PSA outcome. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):679-84. doi: 10.1016/j.ijrobp.2008.05.003. Epub 2008 Oct 27. PMID 18963537
• Grimm P, Billiet I, Bostwick D, Dicker AP, Frank S, Immerzeel J, Keyes M, Kupelian P, Lee WR, Machtens S, Mayadev J, Moran BJ, Merrick G, Millar J, Roach M, Stock R, Shinohara K, Scholz M, Weber E, Zietman A, Zelefsky M, Wong J, Wentworth S, Vera R, Langley S. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer PMID 22239226
• Morris WJ, Keyes M, Palma D, Spadinger I, McKenzie MR, Agranovich A, Pickles T, Liu M, Kwan W, Wu J, Berthelet E, Pai H. Population-based study of biochemical and survival outcomes after permanent 125I brachytherapy for low- and intermediate-risk prostate cancer. Urology. 2009 Apr;73(4):860-5; discussion 865-7. doi: 10.1016/j.urology.2008.07.064. Epub 2009 Jan 24. PMID 19168203
• Morris WJ, Keyes M, Spadinger I, Kwan W, Liu M, McKenzie M, Pai H, Pickles T, Tyldesley S. Population-based 10-year oncologic outcomes after low-dose-rate brachytherapy for low-risk and intermediate-risk prostate cancer. Cancer. 2013 Apr 15;119(8):1537-46. doi: 10.1002/cncr.27911. Epub 2012 Dec 26. PMID 23280183
• Morton G, Loblaw A, Cheung P, Szumacher E, Chahal M, Danjoux C, Chung HT, Deabreu A, Mamedov A, Zhang L, Sankreacha R, Vigneault E, Springer C. Is single fraction 15 Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer? Radiother Oncol. 2011 Sep;100(3):463-7. doi: 10.1016/j.radonc.2011.08.022. Epub 2011 Sep 14. PMID 21924511
• Wright JL, Izard JP, Lin DW. Surgical management of prostate cancer. Hematol Oncol Clin North Am. 2013 Dec;27(6):1111-35, vii. doi: 10.1016/j.hoc.2013.08.010. PMID 24188255
• Stone NN, Stock RG, Cesaretti JA, Unger P. Local control following permanent prostate brachytherapy: effect of high biologically effective dose on biopsy results and oncologic outcomes. Int J Radiat Oncol Biol Phys. 2010 Feb 1;76(2):355-60. doi: 10.1016/j.ijrobp.2009.01.078. Epub 2009 Jul 23. PMID 19632069

Идентификаторы

NCT: NCT05786742 · HYPO-5

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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