Breast Cancer
Conditions
Keywords
Adjuvant Radiotherapy, regional nodal irradiation, internal mammary node irradiation, ultrahypofractionated radiation therapy, hypofractionated radiation therapy
Brief summary
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.
Detailed description
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).
Interventions
RADIATIONUltra-hypofractionated Regional Nodal Irradiation
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.
RADIATIONModerate Hypofractionated Regional Nodal Irradiation
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.
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Upon confirmation of eligibility and after obtaining informed consent, participants will be randomly assigned in a 1:1 ratio to either Arm A (Ultra-Hypofractionated regimen) or Arm B (Moderate hypofractionated regimen). To ensure a balance of key prognostic factors, randomization will be performed using a stratified block design, with stratification by pathologic nodal status (pN1 vs. pN2-3), and participating centers.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide a signed and dated informed consent form (ICF) before the initiation of any trial-specific procedures. 2. Age ≥ 18 years. 3. Histologically confirmed invasive breast cancer. 4. Have received breast-conserving surgery or mastectomy with axillary staging, including sentinel lymph node biopsy, targeted axillary dissection and/or axillary lymph node dissection. 5. Tumor stage is classified as T1, T2, or T3, as defined by the AJCC Cancer Staging Manual, 8th Edition. 6. Meeting at least one of the following conditions: 1. Pathological nodal status of pN2 or pN3a; 2. Pathological nodal status of pN1 with one or more of the following high-risk factors: (I), Age \< 40 years. (II), Tumor location in the central or inner quadrant. (III), Estrogen Receptor (ER) negative. (IV), Presence of lymphovascular invasion (LVI). (V), Histological grade III. (VI), Patients presenting with clinical stage cN2-3a before neoadjuvant treatment. 7. Pathologically negative surgical margins, defined as "no ink on tumor." 8. Karnofsky Performance Status (KPS) score ≥ 80. 9. Documented biomarker status for Estrogen Receptor (ER), Progesterone Receptor (PR), HER2, and Ki-67. 10. Sufficient wound healing from surgery, with no signs of active infection at the intended radiation site.
Exclusion criteria
1. Nodal stage is classified as N3b or N3c, as defined by the AJCC Cancer Staging Manual, 8th Edition. 2. Has undergone or is planning immediate breast reconstruction with a permanent implant or tissue expander. 3. Evidence of distant metastatic disease. 4. Diagnosis of synchronous bilateral invasive breast cancer or a history of prior invasive cancer in either breast. 5. History of prior radiation therapy to the chest, axillary, or supraclavicular regions. 6. Known active collagen vascular diseases, particularly systemic lupus erythematosus or scleroderma, which are contraindications to radiotherapy. 7. Presence of any severe, uncontrolled co-morbidity or medical condition that, in the investigator's judgment, would render the participant unsuitable for the study, compromise protocol compliance, or confound the interpretation of study results. 8. History of any other malignancy within the 5 years before enrollment, with the exception of adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix. 9. Participants who are pregnant or lactating at the time of study enrollment. (Note: In accordance with the standards of each participating institution, women of childbearing age are required to undergo pregnancy testing within 2 weeks prior to randomization.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Breast Cancer Recurrence-Free Survival (IBC-RFS) | 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Radiation-Induced Toxicity | From start of radiotherapy through 90 days after completion of radiotherapy | 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. |
| Late Radiation-Induced Toxicity | From 90 days after completion of radiotherapy to 10 years | 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 |
| Overall Survival (OS) | 10 years | Time from randomization to death from any cause. |
| Locoregional Recurrence-Free Survival (LRRFS) | 10 years | Time from randomization to the first ipsilateral breast, chest wall, or regional nodal recurrence. |
| Distant Metastasis-Free Survival (DMFS) | 10 years | Time from randomization to the first evidence of distant metastasis. |
| Disease-Free Survival (DFS) | 10 years | 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. |
Countries
China
Contacts
CONTACTLu Cao, PhD, MD
CONTACTJia-Yi Chen, PhD, MD
PRINCIPAL_INVESTIGATORJia-Yi Chen, PhD, MD
Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
PRINCIPAL_INVESTIGATORLu Cao, PhD, MD
Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed