Hypofractionated Image-Guided Radiotherapy (IGRT) With Organ Motion Mitigation and Urethral Sparing for Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 444
- 试验地点
- 2
- 主要终点
- Treatment-related grade 3 gastrointestinal or genitourinary toxicity adverse events as assessed by NCI v3.0.
研究概览
简要总结
The present study evaluates the safety, feasibility, quality-of-life effects, PSA kinetics, and clinical outcomes of definitive dose-escalated external beam radiotherapy for localized adenocarcinoma of the prostate.
Eligible patients will have biopsy-proven localized prostate adenocarcinoma without radiographic evidence of regional or distant metastases and without MRI evidence of radiographic T3/T4 disease. Patients may have low-risk, intermediate-risk, or selected high-risk disease. Previous or concomitant hormonal therapy is allowed but is not required, provided prior hormonal therapy was not given for more than 6 months before protocol therapy.
Patients enrolled in the study will receive image-guided volumetric modulated arc radiotherapy (IGRT-VMAT) to 45 Gy in five fractions of 9 Gy each, delivered on five consecutive treatment days unless a clinically or operationally justified interruption is required. Treatment will use organ-motion mitigation, urethral localization, online target tracking, urethral sparing, and treatment-planning quality assurance procedures designed to support normal tissue sparing and accurate radiation delivery. A rectal balloon with air filling will be used for prostate immobilization and anatomical reproducibility, and a urethral catheter loaded with beacon transponders will be used for set-up reproducibility and online tracking.
Patients will be followed at approximately 1 month after treatment, then at approximately 3, 6, 9, and 12 months, and every 6 months thereafter through 60 months. Patients will be followed for a minimum of 5 years. Follow-up assessments will include physician-graded gastrointestinal and genitourinary toxicity using NCI CTCAE v4.0, patient-reported urinary, bowel, and sexual quality-of-life outcomes using validated instruments including EPIC, IPSS, and IIEF questionnaires, and serum PSA testing. Biochemical relapse-free survival will be assessed using the Phoenix definition, and recurrence patterns will be summarized from clinically indicated imaging.
详细描述
This is a prospective, single-arm phase II study of definitive ultra-hypofractionated image-guided radiotherapy for localized prostate adenocarcinoma. The study is designed to evaluate the acute and late safety profile, feasibility, patient-reported quality-of-life outcomes, PSA kinetics, biochemical relapse-free survival, and clinical outcomes of dose-escalated IGRT-VMAT using organ-motion mitigation and urethral sparing.
Patients will receive 45 Gy in 5 fractions of 9 Gy each. Treatment planning will use CT/MRI-based target and organ-at-risk delineation. The protocol incorporates a rectal balloon for prostate stabilization and anatomical reproducibility, a urethral catheter loaded with beacon transponders for urethral localization and online motion tracking, and inverse dose-painting to reduce urethral dose when compatible with target coverage and disease anatomy. Erectile-related structures, including the neurovascular bundles, urogenital diaphragm, and penile bulb, may be contoured and recorded for quality-of-life and dosimetric analyses.
The primary safety assessments are treatment-related Grade 3 or higher gastrointestinal or genitourinary toxicity occurring from the first protocol fraction through 90 days after treatment completion, and treatment-related late Grade 2 or higher gastrointestinal or genitourinary toxicity occurring more than 90 days through 5 years after completion of radiotherapy. Late Grade 3 or higher gastrointestinal or genitourinary toxicity will be summarized separately. Clinically meaningful deterioration from baseline in urinary, bowel, and sexual patient-reported outcomes will be evaluated as a key safety and quality-of-life assessment.
Secondary assessments include PSA kinetics, biochemical relapse-free survival using the Phoenix definition, quality-of-life changes measured by EPIC, IPSS, and IIEF instruments, erectile and sexual function preservation, associations between clinical or dosimetric factors and outcomes, hormonal therapy exposure, and patterns of recurrence on clinically indicated imaging.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •Signed study-specific informed consent.
- •Histologic confirmation of adenocarcinoma of the prostate by biopsy.
- •Localized low-risk, intermediate-risk, or selected high-risk adenocarcinoma of the prostate. Selected high-risk disease is limited to patients with no MRI evidence of radiographic T3/T4 disease and no radiographic regional or distant metastases.
- •No direct evidence of regional or distant metastases after appropriate staging studies.
- •Previous or concomitant hormonal therapy is allowed but not required. - Previous hormonal therapy must not have been given for more than 6 months before protocol therapy.
- •Age ≥40 years.
- •Performance status 0-
- •IPSS score ≤20; alpha blockers are allowed.
- •CT- or ultrasound-based prostate volume estimate ≤150 grams.
- •Participants meeting any of the following criteria are ineligible:
- •Metastatic prostate cancer on imaging studies.
- •MRI evidence of radiographic T3 or T4 disease.
- •Previous pelvic radiotherapy.
- •Previous surgery for prostate cancer.
- •Previous hormonal therapy given for more than 6 months before protocol therapy.
- •History of Crohn's disease or ulcerative colitis.
- •Significant obstructive urinary symptoms, defined as IPSS >
- •Significant psychiatric illness that would interfere with protocol participation.
- •Severe active comorbidity that, in the investigator's judgment, would preclude safe protocol therapy or required follow-up.
排除标准
- •Metastatic disease from prostate cancer on imaging studies MRI evidence of radiographic T3, T4;
- •Previous pelvic radiotherapy;
- •Previous surgery for prostate cancer;
- •Previous hormonal therapy given for more than 6 months prior to therapy;
- •History of Crohn's Disease or Ulcerative Colitis;
- •Previous significant obstructive symptoms;
- •Significant psychiatric illness;
- •Severe, active co-morbidity as defined in section 3.
研究组 & 干预措施
Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy
Participants will receive definitive dose-escalated image-guided volumetric modulated arc radiotherapy for localized prostate adenocarcinoma. Radiotherapy will be delivered to 45 Gy in 5 fractions of 9 Gy each over 5 consecutive days, using organ-motion mitigation, urethral localization, online target tracking, urethral sparing, rectal balloon stabilization, and protocol-specified treatment planning and quality assurance procedures.
干预措施: Ultra-hypofractionated IGRT-VMAT with organ-motion mitigation and urethral sparing (Radiation)
Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy
Participants will receive definitive dose-escalated image-guided volumetric modulated arc radiotherapy for localized prostate adenocarcinoma. Radiotherapy will be delivered to 45 Gy in 5 fractions of 9 Gy each over 5 consecutive days, using organ-motion mitigation, urethral localization, online target tracking, urethral sparing, rectal balloon stabilization, and protocol-specified treatment planning and quality assurance procedures.
干预措施: Rectal balloon with air filling (Device)
Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy
Participants will receive definitive dose-escalated image-guided volumetric modulated arc radiotherapy for localized prostate adenocarcinoma. Radiotherapy will be delivered to 45 Gy in 5 fractions of 9 Gy each over 5 consecutive days, using organ-motion mitigation, urethral localization, online target tracking, urethral sparing, rectal balloon stabilization, and protocol-specified treatment planning and quality assurance procedures.
干预措施: Urethral catheter loaded with beacon transponders (Device)
结局指标
主要结局
Treatment-related grade 3 gastrointestinal or genitourinary toxicity adverse events as assessed by NCI v3.0.
时间窗: 5 years
Expanded Prostate Cancer Index Composite (EPIC) Questionnaire to measure quality of life.
时间窗: 5 years
International Index of Erectile Function (IIEF) Questionnaire to measure quality of life.
时间窗: 5 years
International Prostate Symptom Score (IPSS) Questionnaire to measure quality of life.
时间窗: 5 years
Changes in PSA biochemical parameter measurements (Phoenix Definition).
时间窗: 5 years
Acute treatment-related Grade ≥3 gastrointestinal or genitourinary toxicity
时间窗: From first protocol fraction through 90 days after completion of radiotherapy
Incidence of treatment-related Grade 3 or higher gastrointestinal or genitourinary adverse events, graded using NCI CTCAE version 4.0.
Late treatment-related Grade ≥2 gastrointestinal or genitourinary toxicity
时间窗: More than 90 days through 60 months after completion of radiotherapy
Incidence of treatment-related late Grade 2 or higher gastrointestinal or genitourinary adverse events, graded using NCI CTCAE version 4.0. Late Grade 3 or higher toxicity will be summarized separately.
次要结局
- Change from baseline in urinary quality of life(Baseline; approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months)
- Change from baseline in bowel quality of life(Baseline; approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months)
- Change from baseline in sexual function(Baseline; approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months)
- PSA kinetics after radiotherapy(Approximately 1, 3, 6, 9, and 12 months; then every 6 months through 60 months)
- Biochemical relapse-free survival(Through 60 months or longer after completion of radiotherapy)
- Patterns of recurrence(Through 60 months or longer after completion)
- Correlation of clinical and dosimetric variables with toxicity and quality-of-life outcomes (EPIC-26)(Through 60 months after completion of radiotherapy)
研究者
Carlo Greco, MD
Director Department of Radiation Oncology
Fundacao Champalimaud