Molecular Subtype-Guided Postoperative Radiotherapy for Phyllodes Tumor of the Breast: A Randomized Controlled Trial

N/ANot Yet RecruitingNCT07657169

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University160 enrolled

Overview

Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm, and the role of postoperative radiotherapy (PORT) remains controversial. Our team has previously established a molecular subtyping system for PT, classifying patients into four subtypes. Among them, the malignant novel 1/2 (MN1/MN2) subtypes exhibit extremely high risk of local recurrence, and retrospective data suggest that PORT may significantly improve local control in these subtypes. This study aims to evaluate the efficacy and safety of molecular subtype-guided postoperative radiotherapy (PORT) in patients with MN-subtype phyllodes tumor of the breast. This prospective, multicenter, open-label, randomized controlled trial plans to enroll 160 patients with molecularly confirmed MN1 or MN2 subtype who have undergone R0 resection. Patients will be randomized in a 1:1 ratio to either the PORT group or the observation-only group, with stratification by negative margin width (\<1 cm vs. ≥1 cm) and molecular subtype (MN1 vs. MN2). The primary endpoint is 2-year local recurrence-free survival (LRFS). Secondary endpoints include distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), and the incidence of acute and late radiotherapy-related toxicities. By using an innovative molecular subtyping system to precisely select the target population, this study seeks to assess the benefit and safety of PORT in MN-subtype phyllodes tumors. The results are expected to provide the highest level of evidence for this specific subgroup, advance treatment strategies toward "molecular subtype-guided precision radiotherapy," improve patient outcomes, and inform future clinical guidelines.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

160

Interventions

Postoperative Radiotherapy (PORT)RADIATION

Radiotherapy delivered after R0 resection. For breast-conserving surgery: whole-breast irradiation (50 Gy in 25 fractions, 2 Gy/fraction, 5 fractions/week) followed by sequential tumor bed boost (10-16 Gy in 5-8 fractions, 2 Gy/fraction). For mastectomy: chest wall irradiation (50 Gy in 25 fractions). Techniques allowed: IMRT, VMAT, or TOMO. No routine regional nodal irradiation unless pathologically confirmed nodal involvement. Target volume and organ-at-risk constraints as per protocol (e.g., ipsilateral lung Dmean \<15 Gy, heart Dmean \<5 Gy for left-sided tumors). Acute and late toxicities assessed by CTCAE v5.0.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Female patients aged ≥18 years and ≤75 years. 2. Histologically confirmed breast phyllodes tumor (PT) by the central laboratory, with molecular classification as MN1 or MN2 subtype via transcriptome sequencing or IHC; 3. Primary or ipsilateral local recurrence following R0 resection (negative margins) before enrollment; 4. Pathologically confirmed borderline or malignant PT; 5. No evidence of distant metastasis (M0); 6. ECOG performance status 0-1; 7. Signed informed consent before treatment; 8. Expected randomization and study entry within 8-12 weeks (no later than 16 weeks) after surgery. Exclusion Criteria: 1. Previous radiation to the same-side breast or chest; 2. women, or those of childbearing potential refusing effective contraception; Pregnancy, lactation, or refusal of contraception by fertile subjects; 3. Grade III-IV bone marrow suppression: WBC≤1.9\*109/L，ANC≤0.9\*109/L，PLT≤49\*109/L，AST, ALT≥2\*ULN; 4. Significant diarrhea, severe active infection, uncontrolled systemic disease, interstitial lung disease, active connective tissue disease, or LVEF \< 50%; 5. Significant diarrhea, severe active infection, uncontrolled systemic disease, interstitial lung disease, active connective tissue disease, or LVEF \< 50%; 6. Prior or planned systemic anti-tumor therapy (chemotherapy, targeted therapy, immunotherapy, or investigational agents) during the study; 7. Participation in other clinical trials that precludes study inclusion; 8. Any other condition that, in the opinion of the investigator, renders the patient unsuitable for the trial.

Locations (4)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

The Second Hospital of Shandong University

Jinan, Shandong, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Outcomes

Primary Outcomes

2-year Local Recurrence-Free Survival (LRFS)

Time from randomization to the first documented locoregional recurrence (ipsilateral breast/chest wall or regional lymph nodes) confirmed by imaging and/or pathology, or death from any cause, whichever occurs first. Patients alive without locoregional recurrence are censored at the date of last known follow-up.

Time frame: From randomization up to 2 years post-randomization (primary analysis at 2 years)

Secondary Outcomes

Distant Metastasis-Free Survival (DMFS)

Time frame: From randomization up to 5 years (primary analysis for secondary endpoints will be performed at 2 years, with extended follow-up up to 5 years)

Disease-Free Survival (DFS)

Time frame: From randomization up to 5 years (primary analysis of secondary endpoints at 2 years, with extended follow-up to 5 years)

Overall Survival (OS)

Time frame: From randomization up to 5 years

Incidence of Acute and Late Radiotherapy-Related Toxicities

Proportion of patients experiencing adverse events (AEs) assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Acute toxicity is defined as events occurring within 90 days after start of radiotherapy; late toxicity as events occurring \>90 days after start of radiotherapy. Includes radiation dermatitis, radiation pneumonitis, cardiac toxicity, rib fracture, breast/chest wall fibrosis, and secondary malignancies.

Time frame: From start of radiotherapy up to 5 years post-randomization (acute: within 90 days; late: from 90 days to 5 years)