Image Guided Intensity Modulated External Beam Radiochemotherapy and MRI Based Adaptive BRAchytherapy in Locally Advanced CErvical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- overall survival
研究概览
简要总结
The research group on adaptive image-guided radiotherapy for locally advanced cervical carcinoma completed the protocol for the EMBRACE II study in October 2018. This study will be carried out in the next few years at the University Clinic for Radiotherapy at the Medical University of Vienna and other international partner institutes. EMBRACE II builds on the findings of the current EMBRACE study. These are already implemented in everyday clinical practice in order to further improve the accuracy of the entire therapy of cervical carcinomas, using state-of-the-art techniques of tele- and brachytherapy. The aim of the EMBRACE II study is to maintain and enhance the excellent local tumor control as well as the nodal and systemic control for all tumor stages while minimizing the adverse reaction rates for all affected organs (rectum, sigmoid, urinary bladder, and vagina) to increase the quality of life of patients with cervical carcinomas.
详细描述
The standard treatment of locally advanced cervical cancer is radio-chemotherapy including external beam radiotherapy (EBRT), brachytherapy (BT) and concomitant chemotherapy with weekly Cisplatin. Image Guided Adaptive Brachytherapy (IGABT), with repetitive MRI regarded as gold standard, is increasingly recognized as the new paradigm replacing 2D BT and spreading throughout the world. This spread is at present predominantly in Europe, North America and in many places in Asia. The Gyn GEC ESTRO Recommendations I-IV have been used as the conceptual frame for these developments during the last decade and are now embedded into the new ICRU/GEC ESTRO report 88 (International Commission on Radiation and Units) which is being published in 2015.
Beside increasing mono-institutional clinical experience - also reported in literature - there is increasing clinical evidence and analyses from multi-institutional studies, in particular RetroEMBRACE (n=731) and EMBRACE (n>1350) about dose volume effects and outcome. The mature RetroEMBRACE clinical outcome data and dose volume effect analysis for disease outcome show an improved excellent local and pelvic control and survival and significant dose volume effects for IGABT. Overall treatment time was found to have significant impact on local control, and in addition, volume effects of EBRT were found (IMRT vs. 3D CRT) with impact on morbidity and quality of life. Furthermore, dose effects of chemotherapy (≥5 cycles) were found to have impact on survival in advanced disease. Comprehensive analyses from both large patient cohorts reveal further relevant treatment parameters with major impact on disease outcome, morbidity and quality of life. In the international community the results from the EMBRACE studies are regarded as benchmark for future clinical research in this field. Based on the large success of the RetroEMBRACE and EMBRACE studies, the EMBRACE study and research group decided to continue the clinical research work and to initiate a consecutive EMBRACE II study with interventions derived from the evidence collected within the EMBRACE studies.
INTERVENTIONS, AIMS AND HYPOTHESES
The EMBRACE II interventions address local, nodal and systemic treatment as well as exposure of organs at risk:
- Increased use of IC/IS (intracavitary/interstitial) technique in BT
- Reduction of vaginal source loading
- Systematic utilisation of IMRT
- Utilisation of daily IGRT (set-up according to bony structures)
- EBRT target concept related to the primary tumour; concepts for organ at risk (OAR) contouring
- EBRT dose prescription and reporting
- Adaptation of EBRT nodal elective CTV according to risk of nodal and systemic recurrence
- Systematic application of simultaneous chemotherapy
- Reduction of overall treatment time
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
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Cancer of the uterine cervix considered suitable for curative treatment with definitive radio-(chemo)therapy including MRI guided BT
- •Positive biopsy showing squamous-cell carcinoma, adenocarcinoma or adeno-squamous cell carcinoma of the uterine cervix.
- •Staging according to FIGO and TNM guidelines
- •MRI of pelvis at diagnosis is performed
- •MRI, CT or PET-CT of the retroperitoneal space and abdomen at diagnosis is performed
- •MRI with the applicator in place at the time of (first) BT will be performed
- •Para-aortic metastatic nodes below L1-L2 are allowed
- •Patient informed consent
排除标准
- •Other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin
- •Small cell neuroendocrine cancer, melanoma and other rare cancers in the cervix
- •Metastatic disease above and beyond the retroperitoneal para-aortic L1-L2 interspace
- •Previous pelvic or abdominal radiotherapy
- •Previous total or partial hysterectomy
- •Combination of preoperative radiotherapy with surgery
- •Patients receiving BT only
- •Patients receiving EBRT only
- •Patients receiving neo-adjuvant chemotherapy or other forms of antineoplastic treatment apart from weekly concomitant cisplatin (40 mg/2). However, adjuvant chemotherapy in the form of 4 courses of 3 weekly Carboplatin (AUC 5) and Paclitaxel (155 mg/m2) is allowed according to departmental policy.
- •Contra indications to MRI
- •Contra indications to BT
研究组 & 干预措施
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: Increased use of IC/IS technique in BT (Radiation)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: Reduction of vaginal source loading (Radiation)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: EBRT target concept related to the primary tumor (CTV-T) and internal motion; concepts for OAR contouring (Radiation)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: Systematic utilisation of IMRT (Radiation)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: Utilisation of daily IGRT (set-up according to bony structures) (Radiation)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: EBRT dose prescription and reporting (Radiation)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: Adaptation of EBRT nodal elective CTV according to risk of nodal and systemic recurrence (Radiation)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: Systemic application of simultaneous chemotherapy (Drug)
Standard arm
General and specific aims of EMBRACEII as well as the multiple quantitative hypotheses are based on technical data, dose volume parameters and clinical results of the prospective observational study EMBRACEI (NCT00920920, 3 year data 2015) and the retrospective RetroEMBRACE (3/5 year data 2015). The performance of EMBRACE II interventions and clinical outcome in terms of disease- (local, nodal, systemic control, OS, CSS) and morbidity-outcome (various organs and endpoints) is thus based on recent clinical evidence with radiochemotherapy and image guided adaptive brachytherapy. The expected effect of EMBRACE II interventions on clinical outcome is estimated from comparative analyses of interventions in subgroups of Retro-/EMBRACE (partly published). Based on the Retro-/EMBRACE benchmark, the estimated outcome including a confidence interval is quantified for each clinical endpoint in the overall cohort as well as different subgroups for an overall expected patient number of 1000.
干预措施: Reduction of overall treatment time (Other)
结局指标
主要结局
overall survival
时间窗: 5 years
local control
时间窗: 5 years
health-related quality of life: social functioning
时间窗: 5 years
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire. Scores ranging from 0 to 100, higher scores indicating better functioning.
nodal control
时间窗: 5 years
systemic control
时间窗: 5 years
health-related quality of life: role functioning
时间窗: 5 years
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire. Scores ranging from 0 to 100, higher scores indicating better functioning.
overall morbidity
时间窗: 5 years
health-related quality of life: physical functioning
时间窗: 5 years
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire. Scores ranging from 0 to 100, higher scores indicating better functioning.
次要结局
- cancer specific survival(5 years)
- disease specific survival(5 years)
研究者
Richard Pötter
Principal investigator
Medical University of Vienna