For patients with breast cancer, regional nodal irradiation (RNI) can significantly reduce the risks of recurrence and mortality. Moderate hypofractionated regimens (40 to 42.5 Gy in 15 to 16 fractions over 3 weeks) is the established standard of care for RNI. Nevertheless, for the majority of patients, a three - week treatment duration is still regarded as lengthy. Although the ultra-hypofractionated regimen (26 Gy in 5 fractions over 1 week) has been proven non-inferior to the moderate hypofractionated regimen for whole breast irradiation, unambiguous evidence supporting its use in comprehensive RNI remains lacking, especially in high risk patients requiring internal mammary node irradiation (IMNI). This prospective, non-inferiority trial is designed to address this evidence gap by evaluating whether a one-week, ultra-hypofractionated regimen (26 Gy in 5 fractions) is non-inferior to the three-week regimen (40 Gy in 15 fractions) for comprehensive RNI, including IMNI.
The study intervention is RNI delivered using modern techniques, including Intensity-Modulated Radiation Therapy (IMRT), Volumetric Modulated Arc Therapy (VMAT) or Intensity-Modulated Proton Therapy (IMPT). Technical parameters for treatment delivery, such as target delineation and OARs dose constraints, will be standardized across both arms. The investigational component is the randomized comparison of the ultra-hypofractionated regimen (26 Gy in 5 fractions over one week) and the moderate hypofractionated regimen (40 Gy in 15 fractions over three weeks).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,950
26 Gy in 5 fractions over 1 week (5.2 Gy per fraction, once daily). Treatment targets include ipsilateral supraclavicular, infraclavicular, internal mammary regions, chest wall or whole breast, and any portion of the undissected axilla at risk. Sequential tumor bed boost of 10.4 Gy in 2 fractions (5.2 Gy per fraction) for patients after breast-conserving surgery.
40.05 Gy in 15 fractions over 3 weeks (2.67 Gy per fraction, once daily). Treatment targets include ipsilateral supraclavicular, infraclavicular, internal mammary regions, chest wall or whole breast, and any portion of the undissected axilla at risk. Simultaneous Integrated Boost of 48 Gy in 15 fractions (3.2 Gy per fraction) for patients after breast-conserving surgery.
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, China
Invasive Breast Cancer Recurrence-Free Survival (IBC-RFS)
IBC-RFS, defined as time from randomization until any first invasive ipsilateral breast, chest wall, regional, or distant recurrence, or death from breast cancer. Data for patients who are alive and free of an event at the time of final analysis or are lost to follow-up will be censored at the date of last contact.
Time frame: 5 years
Acute Radiation-Induced Toxicity
Incidence of any grade 1 or higher acute radiation-induced toxicity occurring from the start of radiotherapy through 90 days after completion of radiotherapy, graded per CTCAE v5.0, RTOG Acute Radiation Morbidity Scoring Criteria and LENT/SOMA Scoring Scale.
Time frame: From start of radiotherapy through 90 days after completion of radiotherapy
Late Radiation-Induced Toxicity
Incidence of any grade 1 or higher radiation-induced toxicity event occurring \>90 days after radiotherapy completion, graded using CTCAE v5.0, RTOG/EORTC Late Radiation Morbidity Scoring Schema, and LENT/SOMA Scoring Scale
Time frame: From 90 days after completion of radiotherapy to 10 years
Overall Survival (OS)
Time from randomization to death from any cause.
Time frame: 10 years
Locoregional Recurrence-Free Survival (LRRFS)
Time from randomization to the first ipsilateral breast, chest wall, or regional nodal recurrence.
Time frame: 10 years
Distant Metastasis-Free Survival (DMFS)
Time from randomization to the first evidence of distant metastasis.
Time frame: 10 years
Disease-Free Survival (DFS)
Time from randomization to first occurrence of ipsilateral breast cancer recurrence (invasive or DCIS), locoregional recurrence (chest wall or regional lymph nodes), distant metastasis, contralateral invasive breast cancer, or death from any cause.
Time frame: 10 years
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