A Phase III Randomized Trial of Partial Versus Whole Breast Radiotherapy in Clinically Node-Negative Early Breast Cancer Omitting Sentinel Lymph Node Biopsy (APROOB Trial)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 520
- 试验地点
- 1
- 主要终点
- 5-Year Recurrence-Free Survival Rate
研究概览
简要总结
This is a multicenter, randomized, phase III non-inferiority trial in women aged 40 years or older with clinically node-negative (cN0), pathologically pT1 (≤2 cm), grade 1-2, lymphovascular invasion (LVI)-negative invasive breast cancer treated with breast-conserving surgery (BCS) in whom sentinel lymph node biopsy (SLNB) was omitted (pNx). Eligible patients are randomized 1:1 to partial breast irradiation (PBI) or whole breast irradiation (WBI). The primary aim is to determine whether PBI is non-inferior to WBI with respect to the 5-year recurrence-free survival (RFS) rate. Secondary aims include comparison of axillary recurrence, overall survival, locoregional recurrence, treatment-related toxicity, and quality of life between arms.
详细描述
Background and rationale. PBI has shown oncologic outcomes comparable to WBI in low-risk early breast cancer in several randomized trials (e.g., IMPORT LOW, RAPID, GEC-ESTRO, Florence). Separately, SLNB omission has demonstrated oncologic safety in clinically node-negative patients (e.g., SOUND, INSEMA, BOOG). However, the long-term oncologic safety of combining SLNB omission with PBI has not been established. Because pathologic nodal status is unknown in SLNB-omitted patients, occult nodal micrometastasis cannot be fully excluded despite cN0 status, and the reduced treatment volume of PBI relative to WBI may theoretically increase the risk of axillary or regional nodal recurrence. The strict eligibility criteria (negative axillary ultrasound, pT1, grade 1-2, LVI-negative, single lesion, negative margins) are intended to limit the absolute magnitude of this residual risk.
Design. Eligible, consented patients are centrally randomized 1:1 to WBI or PBI, with block randomization stratified by age (<50 vs ≥50 years), tumor size (≤1 cm vs >1 cm), and hormone receptor status (HR+/HER2- vs other).
Quality assurance. For the first 3 patients enrolled at each participating institution, central review is performed on CT simulation images, CTV/PTV/OAR contours, axillary level I-III contours, treatment plans with dose-volume histograms (DVH), and dose/fractionation data. Central review verifies ESTRO-consistent target definition, OAR contouring adequacy, protocol-compliant dose prescription, PTV coverage and OAR dose constraints, axillary level I-III dosimetry, and confirms that high-tangent technique or regional nodal irradiation (RNI) is not used.
Follow-up schedule. V1 (end of RT); V2 (3 weeks post-RT); V3 (6 months); V4 (12 months); V5 (annually, years 2-4); V6 (5 years). Annual mammography and breast ultrasound are performed; additional imaging is performed if recurrence is suspected. Extended follow-up to 10 years is planned for long-term oncologic safety and late toxicity (breast cancer-specific survival, overall survival, late locoregional recurrence, late radiation toxicity)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female ≥40 years with histologically confirmed unilateral invasive breast cancer.
- •No suspicious nodal metastasis on preoperative axillary ultrasound (cN0).
- •Single lesion in the affected breast on preoperative breast ultrasound and mammography.
- •Treated with breast-conserving surgery with pathologically negative margins for the invasive tumor.
- •Sentinel lymph node biopsy not performed at surgery (pNx).
- •Maximum diameter of invasive tumor ≤2 cm on final pathology (pT1).
- •Histologic grade 1 or
- •Signed informed consent prior to enrollment.
排除标准
- •History of malignancy other than breast cancer within 5 years (except adequately treated non-melanoma skin cancer, or carcinoma in situ excluding breast carcinoma in situ).
- •Preoperative diagnosis of carcinoma in situ without axillary nodal sampling, subsequently diagnosed as invasive breast cancer on final pathology with SLNB omitted.
- •Lymphovascular invasion present (LVI+).
- •Multifocal or multicentric tumor in the same breast confirmed radiologically or pathologically.
- •Bilateral or inflammatory breast cancer.
- •Prior radiotherapy to the breast or thorax.
- •Confirmed pathogenic or likely pathogenic variant in a hereditary breast cancer gene (including BRCA1/2).
- •Recurrent breast cancer.
研究组 & 干预措施
Whole Breast Irradiation (WBI)
Whole breast irradiation using 3D conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT).
干预措施: Whole Breast Irradiation (Radiation)
Partial Breast Irradiation (PBI)
Partial breast irradiation targeting the tumor bed with margin, using 3D-CRT or IMRT, sparing the remainder of the breast.
干预措施: Partial Breast Irradiation (Radiation)
结局指标
主要结局
5-Year Recurrence-Free Survival Rate
时间窗: 5 years from randomization
Proportion of patients free from a first RFS event at 5 years. An RFS event is defined as the first occurrence of ipsilateral invasive breast recurrence, ipsilateral regional nodal recurrence (including axillary), distant metastasis, or breast cancer death. Measured from date of randomization to first event.
次要结局
- 5-Year Axillary Recurrence Rate(5 years from randomization)
- 5-year locoregional recurrence rate(5 years from randomization)
- 5-Year Overall Survival(5 years from randomization.)
研究者
Haeyoung Kim
Professor
Samsung Medical Center