The RELAX trial is an open-label, multicenter, non-inferiority, randomized, phase 3 clinical trial. Multiple randomized trials have demonstrated the safety of omitting complete axillary-lymph-node dissection in patients with invasive breast cancer and limited sentinel lymph node metastases. However, the necessity and optimal extent of regional nodal irradiation remains uncertain. The aim of this study is to evaluate whether level I-II axillary irradiation is non-inferior to whole regional nodal irradiation in terms of disease-free survival in clinically node-negative breast cancer patients with 1-2 sentinel lymph node macro-metastases.
PRIMARY OBJIECTIVE: To evaluate whether level I-II axillary irradiation is non-inferior to whole regional nodal irradiation in terms of disease-free survival in clinically node-negative breast cancer patients with 1-2 sentinel lymph node macro-metastases. SECONDARY OBJECTIVES: I. to estimate the difference of overall survival; II. to estimate the difference of ipsilateral regional recurrence; III. to estimate the difference of ipsilateral local regional recurrence; IV. to estimate the difference of distant recurrence; V. to estimate the difference of radiation related toxicities and quality of life. Outline: Patients are randomized in a 1:1 ratio to two treatment arms. Arm A (Level I-II axillary irradiation): Radiation is delivered to the breast after breast conserving surgery(BCS) or chest wall after mastectomy, level I-II axillary lymph nodes. Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant. Arm B (Entire regional nodal irradiation): Radiation is delivered to the breast after BCS or chest wall after mastectomy, whole axillary lymph nodes (levels I-III) and supraclavicular lymph nodes. IMN is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,608
Radiation is delivered to the breast after BCS or chest wall after mastectomy, whole axillary lymph nodes (levels I-III) and supraclavicular lymph nodes. Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant. Both hypofractionated and conventional fractionated radiation therapy are permitted: the conventional fractionated regimen is 50 Gy in 25 fractions of 2 Gy; the hypofractionated schedule is 42.56 Gy in 16 fractions of 2.66 Gy after mastectomy, or 40.05 Gy in 15 fractions of 2.67 Gy after breast-conserving surgery. Tumor bed after breast-conserving surgery is at the discretion of the treating physician, boost doses will be 10\~16 Gy in 5\~8 fractions of 2 Gy or 10.68\~16.2 Gy in 4\~6 fractions of 2.67 Gy.
Radiation is delivered to the breast after BCS or chest wall after mastectomy and low axillary lymph nodes (levels I-II). Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant. Both hypofractionated and conventional fractionated radiation therapy are permitted: the conventional fractionated regimen is 50 Gy in 25 fractions of 2 Gy; the hypofractionated schedule is 42.56 Gy in 16 fractions of 2.66 Gy after mastectomy, or 40.05 Gy in 15 fractions of 2.67 Gy after breast-conserving surgery. Tumor bed after breast-conserving surgery is at the discretion of the treating physician, boost doses will be 10\~16 Gy in 5\~8 fractions of 2 Gy or 10.68\~16.2 Gy in 4\~6 fractions of 2.67 Gy.
Oncology Department, Guizhou Provincial People's Hospital
Guiyang, Guizhou, China
NOT_YET_RECRUITINGThe Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
NOT_YET_RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
NOT_YET_RECRUITINGDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
NOT_YET_RECRUITINGDepartment of Radiation and Medical Oncology，Zhongnan Hospital of Wuhan University
Wuhan, Hubei, China
NOT_YET_RECRUITINGChangde Hospital, Xiangya school of Medicine, Central South University (The first people's hospital of Changde city)
Changde, Hunan, China
NOT_YET_RECRUITINGHunan cancer hospital/The affiliated cancer hospital of xiangya school of medicine,Central South university
Changsha, Hunan, China
NOT_YET_RECRUITINGDepartment of Radiation and Medical Oncology, Affiliated Zhongshan Hospital of Dalian University
Dalian, Liaoning, China
NOT_YET_RECRUITINGCancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital)
Jinan, Shandong, China
NOT_YET_RECRUITINGFudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITING...and 5 more locations
Disease Free Survival (DFS)
Defined as time from randomization until to local, regional, or distant recurrence, or any death, or secondary primary cancer.
Time frame: 5 years
Overall survival (OS)
Defined as the time from randomization to death from any cause.
Time frame: 5 years
Regional Recurrence (RR)
Defined as the time from randomization to the date of the first ipsilateral axillary, supraclavicular, or internal mammary nodal recurrence.
Time frame: 5 years
Local Regional Recurrence (LRR)
Defined as the time from randomization to the date of the first ipsilateral breast, chest wall, axillary, supraclavicular, or internal mammary nodal recurrence.
Time frame: 5 years
Distance Recurrence (DR)
Defined as the time from randomization to the date of the first distant breast cancer recurrence.
Time frame: 5 years
Safety outcomes
The frequency and severity of acute and late radiation-related adverse events are assessed and graded based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. For some events that CTCAE grading are not available, RTOG/the European Organization for Research and Treatment of Cancer (EORTC) late radiation morbidity scale and LENT-SOMA criteria are used.
Time frame: 5 years
Patient-reported outcomes
Assessment of treatment-related symptoms, health-related quality of life via three questionnaires, including the EORTC Quality of Life Questionnaire (EORTC-QLQ-C30; version 3), breast cancer module (QLQ-BR23) and upper limb function via the Quick Disabilities of the Arm, Shoulder and Hand (q-DASH) questionnaire.
Time frame: 5 years
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