Breast Cancer, Radiotherapy
Conditions
Keywords
Breast Cancer, Sentinel Node Macrometastases, Regional Nodal Irradiation, Level I-II Axillary Irradiation
Brief summary
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.
Detailed description
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.
Interventions
RADIATIONEntire 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. 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.
RADIATIONLevel I-II axillary irradiation
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.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female ≥ 18 years of age; 2. Newly diagnosed primary invasive breast cancer; 3. Clinically stage T1-3N0M0; 4. Patients received surgery as first treatment,and have undergone breast conserving-surgery or mastectomy (with or without breast reconstruction) with negative margins; 5. Have one or two macrometastases (\>2 mm) at sentinel lymph node biopsy,and without further axillary lymph node dissection; 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; 7. Will receive endocrine therapy for at least 5 years for estrogen receptor (ER) and/or progesterone receptor (PR) positive patients; will receive anti-HER2 (human epidermal growth factor receptor 2) therapy for 1 year for HER2 positive patients; 8. Radiation therapy must begin no later than 12 weeks after the last dose of adjuvant chemotherapy or the last breast cancer surgery if no adjuvant chemotherapy; 9. Patients have adequate organ function; 10. Acquirement of informed consent.
Exclusion criteria
1. Patients have received neoadjuvant systemic therapy; 2. Clinical stage T4 or IV (metastatic) breast cancer, or presence of regional metastases before surgery; 3. History of any prior ipsilateral or contralateral invasive breast cancer, history of other malignancies except for appropriately treated skin basal cell carcinoma and cervical carcinoma in situ; 4. History of previous radiotherapy towards the ipsilateral chest/lymph nodes. 5. The ipsilateral axillary lymph node dissection or other previous axillary surgery; 6. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, or psychiatric disease), inability to tolerate radiotherapy or systemic therapy if indicated; 7. Current pregnancy and/or lactation; 8. Inability or unwillingness to comply with protocol requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | 5 years | Defined as time from randomization until to local, regional, or distant recurrence, or any death, or secondary primary cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 5 years | Defined as the time from randomization to death from any cause. |
| Regional Recurrence (RR) | 5 years | Defined as the time from randomization to the date of the first ipsilateral axillary, supraclavicular, or internal mammary nodal recurrence. |
| Local Regional Recurrence (LRR) | 5 years | Defined as the time from randomization to the date of the first ipsilateral breast, chest wall, axillary, supraclavicular, or internal mammary nodal recurrence. |
| Distance Recurrence (DR) | 5 years | Defined as the time from randomization to the date of the first distant breast cancer recurrence. |
| Safety outcomes | 5 years | 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. |
| Patient-reported outcomes | 5 years | 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. |
Countries
China
Contacts
CONTACTXiaoli Yu, MD, PhD
CONTACTLi Zhang, M.D.
PRINCIPAL_INVESTIGATORXiaoli Yu, MD, PhD
Fudan University
PRINCIPAL_INVESTIGATORZhaozhi Yang, MD, PhD
Fudan University
Outcome results
None listed