Trimodal therapy (TMT) consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy is a therapeutic alternative in patients with Muscle-Infiltrating Bladder Cancer who are inoperable or refuse surgery. One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during and between radiotherapy sessions. Standard radiotherapy techniques require large planning target volume margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities. Adaptive radiotherapy allows for the generation of a treatment fraction personalized to a patient's anatomical modification with margin reduction and improves the dosimetric quality of the delivered plans. The hypothesis is that this improvement results in radiation-induced toxicity improvement.
In 2023, the incidence of muscle-infiltrating bladder cancer (MIBC) in France was 14062 cases, 81% of which were in men. The standard treatment for MIBC is cystectomy preceded by neoadjuvant chemotherapy. Trimodal therapy (TMT), consisting of transurethral resection of bladder tumors (TURBT) followed by radiotherapy (RT) and chemotherapy (CT), has emerged as a valuable therapeutic de-escalation alternative in patients who are inoperable or refuse surgery with its physical and psychological sequelae. TMT provides survival outcomes identical to cystectomy in selected patients and allows for bladder preservation in successful cases. TMT is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder who failed intravesical therapy. One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during radiotherapy sessions (intra-fractional movement) and between sessions (inter-fractional movement). To take into account these movements, standard radiotherapy techniques require large planning target volume (PTV) margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities up to 42% and 17% respectively. Adaptive radiotherapy (ART) allows for the generation of a treatment fraction personalized to a patient's anatomical modification. While it was until recently only performed "offline", i.e. between two radiotherapy sessions, it is now possible to perform a daily customization of the radiotherapy session ("online") for a given patient to ensure optimal coverage of the target with minimized margins. ART allows PTV margins reduction for MIBC and improves therefore the dosimetric quality of the delivered plans. The hypothesis is that the dosimetric improvement induced by ART results in radiation-induced toxicity improvement.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Patient will be treated by concomitant: * adaptive radiotherapy 5 days a week for 4 weeks with hypofractionated irradiation 55 Gy / 20 fractions +/- pelvic inclusion 44 Gy/20 fractions (SIB). * chemotherapy if not contraindicated : * Cisplatin : 20 mg/m2/day on day 1 to day 4 and day 22 to day 25 (or 80 mg/m2 during week 1 and 4 of radiotherapy) Or * Gemcitabine: 80 to 100 mg/m2/week Or * Mitomycin C: 12 mg/m2 on day 1 only + 5FU infusion 500 mg/m2/day during 5 days on week 1 and 4 of radiotherapy (alternatively : capecitabine taken twice daily at a dose of 825 per square meter per day on the days of radiotherapy)
Patient will be treated by concomitant: * standard 5 days a week for 4 weeks with hypofractionated irradiation 55 Gy / 20 fractions +/- pelvic inclusion 44 Gy/20 fractions (SIB). * chemotherapy if not contraindicated : * Cisplatin : 20 mg/m2/day on day 1 to day 4 and day 22 to day 25 (or 80 mg/m2 during week 1 and 4 of radiotherapy) Or * Gemcitabine: 80 to 100 mg/m2/week Or * Mitomycin C: 12 mg/m2 on day 1 only + 5FU infusion 500 mg/m2/day during 5 days on week 1 and 4 of radiotherapy (alternatively : capecitabine taken twice daily at a dose of 825 per square meter per day on the days of radiotherapy)
Centre Georges François Leclerc
Dijon, Côte d'or, France
Institut du Cancer de Montpellier
Montpellier, Herault, France
Centre Eugène Marquis
Rennes, Ille et Vilaine, France
Institut de Cancérologie de l'Ouest
Saint-Herblain, Loire Atlantique, France
Centre Oscar Lambret
Lille, Nord, France
Centre de radiothérapie Bayard
Villeurbanne, Rhone, France
Centre Henri Becquerel
Rouen, Seine Maritime, France
Institut Sainte Catherine
Avignon, Var, France
Centre de radiothérapie Saint-Louis
Toulon, Var, France
Hôpital Tenon
Paris, Île-de-France Region, France
...and 1 more locations
evaluation of the technique of adaptive radiotherapy in terms of acute Gastro-Intestinal toxicity.
rate of patients without acute diarrhea grade ≥2
Time frame: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy
Evaluation of all acute toxicities
description of all acute toxicities according to Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0)
Time frame: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy
Evaluation of all late toxicities
description of all late toxicities according to Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0)
Time frame: from 3 months after the last day of Radiotherapy to 5 years after the last day of Radiotherapy
evaluation of quality of life specific to the cancer disease
Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer - Quality Life Questionnaire (EORTC QLQ-C30)
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life and of the measurements specific to the treatment of bladder cancer with muscle invasion
Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer - Quality Life Questionnaire - Bladder Cancer (EORTC QLQ-BLM30)
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life for patient ≥ 70 years old in order to establish a minimum standardized geriatric assessment
Quality of life will be evaluated using Geriatric COre DatasEt oncogeriatric (GCODE) for patient ≥ 70 years old
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
evaluation of quality of life for patient ≥ 70 years old (Specific to elderly people with cancer)
Quality of life will be evaluated using European Organisation for Research and Treatment of Cancer - Quality Life Questionnaire-Elderly (EORTC QLQ- ELD30) for patient ≥ 70 years old
Time frame: at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.
assessment of disease free survival
time interval from randomization to first carcinologic event as local or distant relapse or death
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of cystectomy free survival
the time interval from randomization to cystectomy
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of overall survival
the time interval from randomization to death from any cause
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of local control rate
The presence of non-muscle-invasive or muscle-invasive bladder cancers evaluate by cystoscopy
Time frame: At 3 and 5 years after the last day of Radiotherapy
assessment of the dosimetric results
Dosimetric results in terms of treatment volume coverage and Organ At Risk protection
Time frame: during tthe radiotherapy for both arms
evaluation of the impact of the adaptive process on fractions execution
Evaluation of duration of the treatment fractions (in minutes) in the two arms. Evaluation of the percentage of fractions fully delivered and the duration of physician/physicist mobilization for the adaptive process
Time frame: during tthe radiotherapy for both arms
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