TARGIT-C(Consolidation) Prospective Phase IV Study of Intraoperative Radiotherapy (IORT) in Patients With Small Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 387
- 试验地点
- 4
- 主要终点
- Local relapse
研究概览
简要总结
This prospective, multicentric single arm phase IV study is based on the protocol of the international TARGIT-A and TARGIT-E study.
Patients ≥ 50 years with small, low-risk breast cancer who are operated but not irradiated show local relapse rates around 6% after 5 years. With adjuvant whole breast radiotherapy (WBRT) the local relapse rate drops to under 1% after 5 years under Tamoxifen (4).
It has been demonstrated (6, 9, 10) that the efficacy of radiation of the tumor bed only in a selected group can be non-inferior to WBRT.
The TARGIT C study should confirm the efficacy of a single dose of intraoperative radiotherapy (IORT) in a well selected group of patients with small breast cancer and absence of risk factors. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines.
Endpoints are the local relapse rate (within 2 cm of the tumor bed), ipsilateral relapse, cancer-specific and overall survival and contralateral breast cancer as well as documentation of quality of life and cosmetic outcome.
The expected local relapse rates are 0.825/1.375% after 3/5 years, respectively. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 1.55/2.4/4% after 1/3/5 years. Power calculations result in 387 patients with a calculated dropout and loss to follow-up rate of 10%, an alpha of 0.05 and a beta of 0.10. There will be only a pre-pathology stratum.
It is a pragmatic trial in which each participating centre has the option to modify entry criteria and criteria for WBRT according to this core protocol after consultation with the steering committee and local ethics committee (e.g. size, free margins). Only centers with access to the Intrabeam® system (Carl Zeiss) can recruit patients into the trial.
详细描述
- Introduction
Randomized studies provide evidence that concerning the overall survival breast conserving surgery (BCS) combined with postoperative radiotherapy is equally effective as modified mastectomy (1, 2, 3). Postoperative radiation decreases the local relapse rate (1, 2) highly significantly in comparison to BCS alone (3). The recent metaanalysis of the Early Breast Cancer Trialists Collaborative Group (EBCTCG (3)) show that the avoidance of 4 local relapses after 5 years can prevent one death in 15 years (4 to 1 rule).
Several studies in the past demonstrated that complete omission of radiotherapy failed in terms of local tumor control. Fyles et al. (4) showed local relapse rates of 8% within a low risk group of patients with tumors of pathological stage T1/T2 and >50 years of age treated with BCS and antihormonal treatment (AHT). By adding postoperative whole breast radiation (WBRT) the rate of local relapse was reduced to 1% after 5 years. This effect was also seen in elderly patients with small tumors. Hughes et al. (5) observed low local relapse rates of 4% for patients treated with AHT only after BCS vs. 1% for patients with additional WBRT after 4 years, evaluating a low-risk group of patients with tumors < 2 cm and > 70 years of age. Apparently, all patients benefit from postoperative WBRT. However, due to the fact that 90% of all local relapses after breast conserving therapy are localized very close to the primary tumor, it might be possible to treat a selected group of patients with a relatively low risk of local recurrence with tumor bed irradiation only. Polgar et al. (6) provided evidence of the non-inferiority of accelerated partial breast irradiation (APBI) in comparison to WBRT in a small randomized trial. Very recently the TARGIT-A data (9, 10) reported a non-inferior efficacy of tumor bed irradiation with single dose intraoperative radiation (Intrabeam System, Carl Zeiss Oberkochen) compared to WBRT regarding local relapse.
By using the Intrabeam System, the intraoperative radiotherapy (IORT) can be given during surgery with protection of the surrounding tissue while applying a biologically highly effective dose to the tissue adjacent to the tumor.
Advantages of IORT are its high precision regarding beam application, its possibility of protection of the skin and the prevention of tumor cell proliferation during the time interval between breast conserving surgery and adjuvant WBRT as well as during fractionated WBRT.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •histologically verified invasive-ductal breast cancer
- •hormone receptor positive (if known)
- •cT1 or small cT2 (≤ 3.5 cm) cN0 cM0
- •≥ 50 years of age
- •informed consent
- •compliance
排除标准
- •extensive intraductal component (EIC)
- •negative hormone receptor status
- •multifocality /-centricity (mammography, breast ultrasound)
- •lymph vessel invasion (L1)
- •clinical signs of distant metastases or clinically suspicious lymph nodes
- •other histology
- •< 50 years
- •missing informed consent or non-compliance
- •bilateral breast cancer at the time of diagnosis
- •known BCRA1/2 gene mutations (genetic testing not required)
- •any exclusion criterion in the local centre´s treatment policy
研究组 & 干预措施
Intraoperative radiotherapy (IORT)
IORT (20Gy) as intervention will be given during breast conserving surgery. If risk factors (Tumor > 3.5 cm, lobular cancer, resection margin < 2 mm*, L1, pN+ mulitfocal/multicentric, EIC, negative hormone receptors) are present, external beam radiotherapy will be added.
* In case of positive margins (<2 mm resection margin) a re-resection should be done
干预措施: Intraoperative radiotherapy (IORT) (Radiation)
结局指标
主要结局
Local relapse
时间窗: 5 years
Local relapse rate within 2 cm of the tumor bed
次要结局
- Toxicity (CTC, LENT SOMA)(5 years)
- General QoL and breast specific QoL (EORTC QLQ C30 + BR23)(5 years)
- Ipsi- or contralateral breast cancer(5 years)
- Survival(5 years)
研究者
Elena Sperk, MD
Head, Clinical Trials Unit, Department of Radiation Oncology Mannheim
Universitätsmedizin Mannheim