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

NCT07657169 | Not Yet Recruiting

• 1 other identifier: SYSKY-2026-390-02
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Radiotherapy, Adjuvant; Prognosis; Molecular Typing; Phyllodes Breast Tumor

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (4)

• Distant Metastasis-Free Survival (DMFS)

  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)

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

• Overall Survival (OS)

  From randomization up to 5 years

• Incidence of Acute and Late Radiotherapy-Related Toxicities

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

Study Arms (2)

Postoperative Radiotherapy (PORT)

EXPERIMENTAL

Patients receive postoperative radiotherapy starting within 8-12 weeks (max 16 weeks) after R0 resection. For breast-conserving surgery: whole-breast irradiation (50 Gy/25 fractions) plus sequential tumor bed boost (10-16 Gy/5-8 fractions). For mastectomy: chest wall irradiation (50 Gy/25 fractions). No routine regional nodal irradiation unless pathologically positive. Acute and late toxicities monitored per CTCAE v5.0.

Radiation: Postoperative Radiotherapy (PORT)

Observation

NO INTERVENTION

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.

Postoperative Radiotherapy (PORT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged ≥18 years and ≤75 years.
• Histologically confirmed breast phyllodes tumor (PT) by the central laboratory, with molecular classification as MN1 or MN2 subtype via transcriptome sequencing or IHC;
• Primary or ipsilateral local recurrence following R0 resection (negative margins) before enrollment;
• Pathologically confirmed borderline or malignant PT;
• No evidence of distant metastasis (M0);
• ECOG performance status 0-1;
• Signed informed consent before treatment;
• Expected randomization and study entry within 8-12 weeks (no later than 16 weeks) after surgery.

You may not qualify if:

• Previous radiation to the same-side breast or chest;
• women, or those of childbearing potential refusing effective contraception; Pregnancy, lactation, or refusal of contraception by fertile subjects;
• Grade III-IV bone marrow suppression: WBC≤1.9\*109/L，ANC≤0.9\*109/L，PLT≤49\*109/L，AST, ALT≥2\*ULN;
• Significant diarrhea, severe active infection, uncontrolled systemic disease, interstitial lung disease, active connective tissue disease, or LVEF \< 50%;
• Significant diarrhea, severe active infection, uncontrolled systemic disease, interstitial lung disease, active connective tissue disease, or LVEF \< 50%;
• Prior or planned systemic anti-tumor therapy (chemotherapy, targeted therapy, immunotherapy, or investigational agents) during the study;
• Any other condition that, in the opinion of the investigator, renders the patient unsuitable for the trial.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (4)

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

Guangzhou, Guangdong, 510120, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518000, China

Location

The Second Hospital of Shandong University

Jinan, Shandong, 250033, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266003, China

Location

Related Publications (9)

• Zheng WH, Long ZQ, Kou J, Sun JY, Li FY, Zhang LL, He ZY. Postoperative radiation therapy in localized breast malignant phyllodes tumors: RPA-derived risk model identifies high-benefit subgroups with local control improvement. Breast. 2025 Dec;84:104617. doi: 10.1016/j.breast.2025.104617. Epub 2025 Oct 22.

  PMID: 41135329 BACKGROUND

• Kim YJ, Kim K. Radiation therapy for malignant phyllodes tumor of the breast: An analysis of SEER data. Breast. 2017 Apr;32:26-32. doi: 10.1016/j.breast.2016.12.006. Epub 2016 Dec 22.

  PMID: 28013032 BACKGROUND

• Ma B, Li X, Zhuang Z, Han M, Zhang Y, Ye F, Bi Z, Deng W, Zhang J, Yang Y, Nie Y. Effects of radiotherapy in borderline and malignant phyllodes tumors after R0 resection: a propensity score analysis. Ther Adv Med Oncol. 2025 Oct 27;17:17588359251387556. doi: 10.1177/17588359251387556. eCollection 2025.

  PMID: 41179117 BACKGROUND

• Varghese SS, Sasidharan B, Manipadam MT, Paul MJ, Backianathan S. Radiotherapy in Phyllodes Tumour. J Clin Diagn Res. 2017 Jan;11(1):XC01-XC03. doi: 10.7860/JCDR/2017/24591.9167. Epub 2017 Jan 1.

  PMID: 28274029 BACKGROUND

• Zhao W, Tian Q, Zhao A, Wang B, Yang J, Wang L, Zhang L, Dong D, Chen L, Yang J. The role of adjuvant radiotherapy in patients with malignant phyllodes tumor of the breast: a propensity-score matching analysis. Breast Cancer. 2021 Jan;28(1):110-118. doi: 10.1007/s12282-020-01135-7. Epub 2020 Aug 3.

  PMID: 32748225 BACKGROUND

• Barth RJ Jr, Wells WA, Mitchell SE, Cole BF. A prospective, multi-institutional study of adjuvant radiotherapy after resection of malignant phyllodes tumors. Ann Surg Oncol. 2009 Aug;16(8):2288-94. doi: 10.1245/s10434-009-0489-2. Epub 2009 May 8.

  PMID: 19424757 BACKGROUND

• Donato AR, Goncalves R, Maesaka JY, Aguiar FN, Soares JM Jr, Ruiz CA, Filassi JR, Baracat EC. Phyllodes tumors of the breast: A comprehensive review of diagnosis, treatment, and follow-up. Clinics (Sao Paulo). 2025 Mar 14;80:100617. doi: 10.1016/j.clinsp.2025.100617. eCollection 2025.

  PMID: 40088524 BACKGROUND

• Zhang H, Tang S, Biskup E, Zhang Y, Yong L, Chen L, Cai F. Long-term Survival After Diverse Therapeutic Modalities in Malignant Phyllodes Tumors of the Breast. Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221121086. doi: 10.1177/15330338221121086.

  PMID: 36000314 BACKGROUND

• Gradishar WJ, Moran MS, Abraham J, Abramson V, Aft R, Agnese D, Allison KH, Anderson B, Bailey J, Burstein HJ, Chen N, Chew H, Dang C, Elias AD, Giordano SH, Goetz MP, Jankowitz RC, Javid SH, Krishnamurthy J, Leitch AM, Lyons J, McCloskey S, McShane M, Mortimer J, Patel SA, Rosenberger LH, Rugo HS, Santa-Maria C, Schneider BP, Smith ML, Soliman H, Stringer-Reasor EM, Telli ML, Wei M, Wisinski KB, Yeung KT, Young JS, Schonfeld R, Kumar R. Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024 Jul;22(5):331-357. doi: 10.6004/jnccn.2024.0035.

  PMID: 39019058 BACKGROUND

MeSH Terms

Conditions

Phyllodes Tumor

Condition Hierarchy (Ancestors)

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Yan Nie

CONTACT

+86 020-81332587; nieyan7@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 18, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)