Personalization of Breast Radiotherapy According to Loco-regional Recurrence Risk and Toxicity Probability
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 854
- 试验地点
- 1
- 主要终点
- Rate of patients without any grade 2 or more fibrosis, nor radio-induced sarcoma
研究概览
简要总结
Our objective is based on a personalized approach of adjuvant breast radiotherapy by selecting patients according to tumor recurrence and toxicity risk.
详细描述
Breast cancer is the most common cancer in women in the world and remains a major public health burden with 25% of all cancer cases and 15% of all cancer deaths among females. The Incidence has increased with the introduction of mammography screening and continues to rise, mainly due to population aging; meanwhile, breast cancer survival has significantly improved over the past decades.
Adjuvant radiotherapy (RT) is an essential component of the treatment. After breast surgery for invasive carcinoma, RT is commonly used and delivered without considering the different tumor subtypes, unless the node involvement risk, because it decreases the rate of local recurrence and by this way, specific mortality. The " one size fits all " approach is widely applied, with two main options: breast or chest wall only radiotherapy or breast or chest wall plus nodes radiotherapy. Rare are the centers that discuss IMRT use, external partial breast irradiation, adaptive breast necessity, etc….
- Breast cancer and loco-regional recurrence risk Ten-year cancer specific survival exceeds 70%, with 89% survival for local and 62% for regional disease. The risk of recurrence is high during the first two years after the initial diagnosis for patients with hormonal receptor (HR)-negative breast cancer, but rapidly decreases below the recurrence risk of HR-positive tumors.
Loco-regional recurrence (LRR) occurs in 5-15% of cases treated with breast conservative surgery (BCS) plus adjuvant radiotherapy (RT) or mastectomy and is considered an independent poor prognostic factor6. The management of LRR requires a multidisciplinary approach. Total mastectomy is the standard of care for isolated LRR after BCS. However, secondary BCS ± RT is an alternative approach that could be discussed case by case.
Parameters to predict the risk of recurrence are those included in the NHS UK updated PREDICT score such as age, node status, tumor grade, proliferation index, Her2 and hormone receptor expression. 2. Adjuvant breast radiotherapy and subcutaneous toxicity probability Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as fibrosis, retraction or telangiectasia with poor cosmetic outcome can have a negative impact on quality of life following breast cancer and a marked effect on subsequent psychological outcome. Multiple factors are known to increase the risk of radiation toxicity including individual radiosensitivity9. While the toxicity risks for patients are well-established, determining an individual's normal tissue radiosensitivity is rarely possible before treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •General criteria (for all cohorts):
- •Women ≥ 18 years old.
- •Invasive breast cancer treated by conservative or radical surgery.
- •Conservative breast cancer surgery or radical mastectomy.
- •Indication of breast irradiation.
- •Extension evaluation of disease will be proven negative (M0).
- •Negative pregnancy test (blood or urine at the choice of investigator), to be carried out within 7 days of registration, for women of childbearing age only.
- •Effective contraception for women of childbearing age
- •Must be geographically accessible for follow-up.
- •Written and dated informed consent.
- •Affiliated to the French national social security system.
- •Cohort A and B:
- •- Low risk of recurrence (all of the criteria)
- •SBR (Scarff Bloom et Richardson grade) grade ≤ 2 (low grade)
- •ER+ and / or PR+ (hormone-receptor positive)
- •Ki67 ≤10%
- •pN- with T3-4 and grade 3 and internal tumor will be considered at high risk of recurrence and will be proposed node irradiation (and will be switched to COHORT C or D).
- •Cohort C and D:
- •- High risk of recurrence (pN+ and at least one of all) adapted from the UK PREDICT
- •ER- and PR-
- •HER2 amplified
- •SBR grade ≥ 3
- •KI67 > 10%
- •Cohort A and C:
- •Low risk of breast toxicities identified by the NovaGray RILA Breast® test
- •Cohort B and D:
- •- High risk of breast toxicities identified by the NovaGray RILA Breast® test
排除标准
- •1. Patients with distant metastases.
- •2. Patients with breast DCIS (ductal carcinoma in situ)
- •Concomitant bilateral breast cancer
- •Previous breast radiotherapy
- •Patients with previous or concomitant other (not breast cancer) malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least five years.
- •6. Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.
- •7. Patients known to be HIV positive (no specific tests are required to determine the eligibility).
- •8. Patients known as hypersensitive to radiation
- •Patients treated with systemic investigational drugs during the present study (Observational cohorts are accepted if the collection of data does not interfere with the current trial)
- •Pregnant or breast-feeding women
- •Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study
- •Person deprived of their liberty or under protective custody or guardianship
研究组 & 干预措施
COHORT A
In this cohort, the patients with low risk of recurrence and a low risk of breast toxicity
干预措施: COHORT A (Radiation)
COHORT B
For this cohort, patients with low risk of recurrence and a high risk of breast toxicity, will receive breast radiotherapy according to the investigator's decision among:
- External partial : 40 Gy in 15 fractions to the partial breast only (tumorectomy bed).
- Exclusive Brachytherapy: 30.1 Gy in 7 fractions or 32.0 Gy in 8 fractions of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days.
- Whole Breast Normo fractionated with Fixed Field Intensity Modulated radiotherapy(IMRT) Technique: 50 Gy in 25 daily fractions over 5 weeks +/- Sequential (+ 16 Gy/8fr) or SIB (simultaneous integrated boost) (60 Gy/25 fr) treatment for boost if applicable.
干预措施: COHORT B (Radiation)
COHORT C
For this cohort, patients with high risk of recurrence and a low risk of breast toxicity, will receive whole breast and nodes Hypofractionated VMAT and a localized simultaneous boost according to the HypoG01 schema protocol:
VMAT Technique, 42.3 Gy in 18 fractions on all target volume on 3.5 weeks +/- SIB boost if need (52.2Gy in 18 fractions).
干预措施: COHORT C (Radiation)
COHORT D
For this cohort, patients with high risk of recurrence and a high risk of breast toxicity, will receive breast radiotherapy based on available clinical trials:
- Whole Breast and Nodes Hypofractionated VMAT with adaptive treatment (margin reduction): HypoG01 Schema with VMAT Technique, 42.3 Gy in 18 fractions on all target volume over 3.5 weeks +/- SIB boost if need (52.2Gy in 18 fr) In case of patient refusal or technique unavailable, a standard treatment available in the center for this indication will be delivered.
干预措施: COHORT D (Radiation)
结局指标
主要结局
Rate of patients without any grade 2 or more fibrosis, nor radio-induced sarcoma
时间窗: at 10 years
Toxicity free survival is defined as the interval between date of inclusion and the occurrence of fibrosis grade 2 or more or radio-induced sarcoma. Patients without event at the analysis will be censored at the date of last follow-up.
次要结局
- Acute toxicity(from the start of RT to 12 weeks post RT)
- Relapse-free survival (RFS) rate(at 3, 5, 10 years)
- Late toxicity(from 12 weeks post RT to 3, 5 and 10 years post RT)
- Local recurrence rate (LRR)(at 3, 5, 10 years)
- Radiation-induced Breast Sarcoma prevalence(at 10 years)
- Overall survival (OS) rate(at 3, 5, 10 years:)