Five Fractions Ultrahypofractionated Whole Breast Radiotherapy and Simultaneous Integrated Boost to the Tumor Bed, for Breast Cancer Patients With Unfavorable Characteristics
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 458
- 试验地点
- 1
- 主要终点
- Local Relapse Free Survival (LRFS)
研究概览
简要总结
This is a prospective, randomized, single-center, non-inferiority interventional clinical trial comparing whole breast irradiation (WBI) to a total dose of 26 Gy in 5 fractions with simultaneous integrated boost (SIB) to the tumor bed to a total dose of 30 Gy, and WBI to a total dose of 40.05 Gy in 15 fractions with SIB to the tumor bed to a total dose of 48 Gy (standard treatment), for young or unfavorable breast cancer patients.
详细描述
The project refers to a study on patients with T1-T3 Nx-N3 breast cancer, aged under 40 years or with unfavorable histology (lobular carcinoma, multifocal tumor, or histological subtypes Luminal B Her2 positive, Hormonal Receptors negative Her 2 positive, Triple Negative Breast Cancer-TNBC-) treated with breast-conserving surgery (BCS) and radiotherapy to the whole breast (+/- lymph node areas) to a total dose of 26 Gy in 5 fractions, with simultaneous boost (SIB) to the tumor bed to the total dose of 30 Gy, that will be compared with the current departmental standard of moderately hypofractionated radiotherapy to the whole breast, to 40.05 Gy in 15 fractions, with SIB to the tumor bed to a total dose of 48 Gy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histological diagnosis of breast cancer
- •Patients younger than 40 years regardless of histological subtype, or patients between 40 and 70 years with lobular carcinoma, histological subtypes Luminal B Her2 positive, or with hormone receptors negative and Her2 positive (ErbB2), or triple negative (TNBC)
- •Signed informed consent
- •Clinical stage T1-T3, Nx-N3
- •Negative surgical margins (≥ 0.2 cm)
- •Clinical M0 in the previous 3 months
- •PS (ECOG) ≤2
- •No previous thoracic radiotherapy
- •Fertile women using contraceptive methods started during oncological treatment
排除标准
- •Patients with favorable characteristics (Luminal A, Luminal B Her2 negative, ≥ 40 years) undergoing partial irradiation
- •Patients who have undergone mastectomy
- •Multicentric tumors
- •Positive or close surgical margins (<0.2 cm)
- •BRCA1/2 positive (only if known)
- •Serious systemic diseases
- •Mental or other disorders that may prevent the patient from signing the informed consent
- •Previous invasive tumor, except skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (for example carcinoma in situ of the oral cavity or bladder)
- •Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
- •Evidence of distant metastases (M1)
- •Contraindication to treatment systemic
- •Pregnant women
- •Non-compliance with the dose limits established in the treatment plan
研究组 & 干预措施
Arm 1- Five fractions radiotherapy
Patients in the study (randomized to arm 1) will be treated to the whole breast to a total dose (TD) of 26 Gy in 5 fractions, with simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed. For each patient, an IMRT (intensity modulated radiotherapy) treatment plan will be created to ensure adequate coverage of the treatment volumes and the tolerability of the Organs At Risk (OAR). Specific, already validated dose-volume constraints will be applied for the evaluation of OARs. The dose-volume histogram (DVH) for the Gross Tumor Volume (GTV), Clinical Target Volume (CTV), PTV, and OAR will be calculated in order to achieve the best optimization in terms of tolerability and efficacy.
干预措施: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed (Radiation)
Arm 2- Fifteen fractions radiotherapy
Patients randomized to arm 2 will be treated according to the standard protocol of our department, delivering adjuvant whole breast irradiation (WBI) to a total dose (TD) of 40.05 Gy in 15 fractions, with simultaneous integrated boost (SIB) to the tumor bed to a TD of 48 Gy.
干预措施: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed (Radiation)
结局指标
主要结局
Local Relapse Free Survival (LRFS)
时间窗: 5 years
o demonstrate the non-inferiority of local control (local relapse free survival - LRFS) of the study treatment (delivered in five fractions) compared to the department's standard WBI treatment (delivered in 15 fractions).
次要结局
- Acute toxicity(3 months)
- Late toxicity(5 years)
- Overall Survival (OS)(From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years)
- Local Control(5 years)
- Ipsilateral Breast Tumor Recurrence (IBTR)(5 years)
- Regional Relapse-Free Survival (RRFS)(From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years)
- Distant Metastasis-Free Survival (DMFS)(From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years)
- Disease-Free Survival (DFS)(From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years)
- Breast Cancer Specific Survival (BCSS)(From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years)
- Cosmesis(5 years)
- Local relapse interim analysis(42 months)
- Modeling of organ movement(15 days)
- Radiomics(5 years)
- Acute toxicity interim analysis(3 months)
- Late toxicity interim analysis(42 months)
- Incidence of Treatment-Emergent Adverse Events as assessed with breast tumor specific quality of life questionnaires(5 years)
- Predictive factors for disease progression(5 years)
- Predictive factors for death(5 years)
- Predictive factors for toxicity(5 years)
- Acute toxicity(1 month)
研究者
Andrei Fodor, MD
Principal Investigator
IRCCS San Raffaele