A Prospective Phase II Randomized Controlled Trial Comparing Ultra-Hypofractionated and Moderately Hypofractionated Proton Radiotherapy Following Breast-Conserving Surgery in Early-Stage Breast Cancer（UPH-BC）
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 312
- Locations
- 1
- Primary Endpoint
- Cosmetic Outcomes
Study Overview
Brief Summary
Breast-conserving surgery (BCS) followed by whole-breast irradiation (WBI) remains the standard therapeutic approach for early-stage breast cancer. Long-term follow-up data from the FAST trial (10-year analysis) demonstrated that the 28.5 Gy/5-fraction regimen exhibited comparable adverse effects to the conventional 50 Gy/25-fraction regimen, with no statistically significant differences in photographic cosmetic assessments at 2 and 5 years post-treatment. The FAST-Forward trial demonstrated comparable 5-year ipsilateral breast tumor recurrence rates (IBTR) and incidence of radiation-related toxicities between ultra-hypofractionated whole-breast irradiation (UH-WBI; 26 Gy in 5 fractions over 1 week) and moderately hypofractionated whole-breast irradiation (MH-WBI; 40 Gy in 15 fractions over 3 weeks). Additionally, no statistically significant difference in cosmetic outcomes was observed between the two regimens at the 2-year follow-up.
Proton radiotherapy enables precise dose delivery to tumor targets while minimizing radiation exposure to surrounding normal tissues, thereby reducing treatment-related toxicities. However, current clinical protocols predominantly employ conventional fractionation for proton therapy, with a paucity of robust evidence evaluating the efficacy and safety of ultra-hypofractionated proton radiotherapy in breast cancer patients. This prospective randomized controlled trial aims to establish high-level scientific evidence for the clinical application of ultra-hypofractionated proton radiotherapy following BCS, ensuring non-inferiority in oncologic control, toxicity profiles, and cosmetic preservation compared to standard regimens.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 40 years
- •Pathologically (cytologically or histologically) confirmed unilateral primary invasive breast carcinoma
- •Breast conserving surgery + sentinel lymph node biopsy/axillary lymph node dissection, pathological stage pT1-2N0M0，negative margins (≥ 2 mm)
- •No distant metastasis confirmed by CT, MRI, bone scan, and PET/CT
- •No prior radiation therapy to the ipsilateral chest or breast
- •ECOG 0 ~ 2 or KPS ≥ 70
Exclusion Criteria
- •Without pathology diagnosis
- •Positive margins or close margins (< 2mm)
- •Lymph nodes or distant metastasis
- •Bilateral breast cancer or patients with a history of contralateral breast cancer
- •Prior radiation therapy to the ipsilateral chest or breast
- •Pregnancy (confirmed by serum or urine β-HCG test) or lactation
Arms & Interventions
moderate hypofractionated proton radiotherapy
Whole Breast Irradiation, at 40 Gy(RBE) in 15 fractions, tumor bed SIB to 48Gy(RBE)
Intervention: moderate hypofractionated proton radiotherapy (Radiation)
ultra-hypofractionated proton radiotherapy
Whole breast radiotherapy, 26 Gy(RBE) in 5 fractions，tumor bed boost with 10Gy(RBE) in 2 fractions.
Intervention: ultra-hypofractionated proton radiotherapy (Radiation)
Outcomes
Primary Outcomes
Cosmetic Outcomes
Time Frame: 2 years
Cosmetic outcomes will be assessed at 2 years after radiotherapy. Changes in breast appearance compared to baseline will be evaluated using the Breast Cancer Treatment Outcome Scale (BCTOS), independently completed by the patient, the treating physician, and a trained research assistant at each follow-up visit. Standardized photographs of the treated breast will be taken at each assessment time point and analyzed using BCCT.core software for objective cosmetic scoring.
Secondary Outcomes
- Acute and late toxicities(5 years)
- Locoregional recurrence (LRR)(5 years)
- Disease-free survival (DFS)(5 years)
- Overall survival (OS)(5 years)
Investigators
Qing Zhang,MD
Principal Investigator
Shanghai Proton and Heavy Ion Center