Effects of Radiotherapy in Borderline and Malignant Phyllodes Tumors After R0 Resection

Effects of Radiotherapy on Recurrence and Survival in Borderline and Malignant Phyllodes Tumors After R0 Resection: a Propensity Score Analysis

Breast phyllodes tumors (PT) are rare fibroepithelial neoplasms originating from stromal tissue and account for less than 1% of all breast tumors. The World Health Organization (WHO) classifies PT into benign, borderline, and malignant subtypes based on pathological features such as mitotic activity, cellular atypia, tumor margin invasion, and stromal composition 1. The presence of malignant heterologous elements characterizes the tumor as malignant 2. Surgery is the primary treatment. However, even after R0 resection, borderline phyllodes tumors (BoPT) and malignant phyllodes tumors (MPT) patients remain face a high risk of local recurrence, with rates of 15%-20% and 25%-30%, respectively. Moreover, metastases occur almost merely in MPT, with a distant metastasis rate reaching 22%.

Adjuvant radiotherapy has attracted attention for its potential to improve local control and reduce recurrence, but the role after R0 resection in PT patients remains unclear. Radiotherapy significantly reduces local recurrence rates in BoPT and MPT but shows no substantial benefit in benign cases. However, a meta-analysis by Yu et al. found that this effect is limited to MPT. Additionally, the effect of radiotherapy on survival rates in PT remains controversial. Most existing studies are retrospective and face limitations such as small sample sizes. The rarity of PT and conflicting evidence of impact of radiotherapy necessitate further study. While prospective trials are difficult due to limited cases, well-designed retrospective studies can offer valuable insights. In this study, the investigators also analyzed prognostic factors and identified subgroups to provide a clinical reference for the application of postoperative radiotherapy in BoPT and MPT patients.

Study Overview

• Status: Completed
• Conditions: Prognosis; Radiotherapy, Adjuvant; Phyllodes Breast Tumor
• Intervention / Treatment: Radiation: Adjuvant Radiotherapy; Procedure: R0 resection

• Study Type: Observational
• Enrollment (Actual): 480

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China, 510050
      • Sun Yat-sen University Cancer Center
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Third Hospital of Nanchang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients pathologically diagnosed with BoPT and MPT who underwent surgery at three medical institutions in China: Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Sun Yat-sen University Cancer Center, and the Third Affiliated Hospital of Nanchang University.

Description

Inclusion Criteria:

• patients who were initially diagnosed with BoPT or MPT and underwent R0 resection surgery

Exclusion Criteria:

• patients who had their initial surgery at other hospitals without accurate baseline data
• patients who received radiotherapy before surgery
• those presenting with initial distant metastasis before treatment
• patients lost to follow-up after treatment
• patients with a history of or concurrent breast cancer or precancerous lesions in the ipsilateral breast or with breast cancer in the contralateral breast

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Phyllodes tumors patients who received radiotherapy afte R0 resection	Radiation: Adjuvant Radiotherapy; Postoperative Radiotherapy with 3D-CRT and IMRT Techniques Following R0 Resection in BoPT and MPT Patients; Procedure: R0 resection; Patients who received R0 resection (complete resection without tumor margin)
Phyllodes tumors patients who received R0 resection alone	Procedure: R0 resection; Patients who received R0 resection (complete resection without tumor margin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year Local Recurrence-free Survival	The time period from the initial R0 resection to either the detection of local recurrence or the final follow-up.	Five years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year Overall Survival	The time from the first R0 resection to either all-cause mortality or the last follow-up.	Five years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Belkacemi Y, Bousquet G, Marsiglia H, Ray-Coquard I, Magne N, Malard Y, Lacroix M, Gutierrez C, Senkus E, Christie D, Drumea K, Lagneau E, Kadish SP, Scandolaro L, Azria D, Ozsahin M. Phyllodes tumor of the breast. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):492-500. doi: 10.1016/j.ijrobp.2007.06.059. Epub 2007 Oct 10.
• Macdonald OK, Lee CM, Tward JD, Chappel CD, Gaffney DK. Malignant phyllodes tumor of the female breast: association of primary therapy with cause-specific survival from the Surveillance, Epidemiology, and End Results (SEER) program. Cancer. 2006 Nov 1;107(9):2127-33. doi: 10.1002/cncr.22228.
• Pandey M, Mathew A, Kattoor J, Abraham EK, Mathew BS, Rajan B, Nair KM. Malignant phyllodes tumor. Breast J. 2001 Nov-Dec;7(6):411-6. doi: 10.1046/j.1524-4741.2001.07606.x.
• Boutrus RR, Khair S, Abdelazim Y, Nasr S, Ibraheem MH, Farahat A, El Sebaie M. Phyllodes tumors of the breast: Adjuvant radiation therapy revisited. Breast. 2021 Aug;58:1-5. doi: 10.1016/j.breast.2021.03.013. Epub 2021 Apr 7.
• Yu CY, Huang TW, Tam KW. Management of phyllodes tumor: A systematic review and meta-analysis of real-world evidence. Int J Surg. 2022 Nov;107:106969. doi: 10.1016/j.ijsu.2022.106969. Epub 2022 Oct 31.
• Li J, Tsang JY, Chen C, Chan SK, Cheung SY, Wu C, Kwong A, Hu J, Hu H, Zhou D, Tse GM. Predicting Outcome in Mammary Phyllodes Tumors: Relevance of Clinicopathological Features. Ann Surg Oncol. 2019 Sep;26(9):2747-2758. doi: 10.1245/s10434-019-07445-1. Epub 2019 May 20.
• Pezner RD, Schultheiss TE, Paz IB. Malignant phyllodes tumor of the breast: local control rates with surgery alone. Int J Radiat Oncol Biol Phys. 2008 Jul 1;71(3):710-3. doi: 10.1016/j.ijrobp.2007.10.051. Epub 2008 Jan 30.
• Moffat CJ, Pinder SE, Dixon AR, Elston CW, Blamey RW, Ellis IO. Phyllodes tumours of the breast: a clinicopathological review of thirty-two cases. Histopathology. 1995 Sep;27(3):205-18. doi: 10.1111/j.1365-2559.1995.tb00212.x.
• Md Nasir ND, Koh VCY, Cree IA, Ruiz BII, Del Aguila J, Armon S, Fox SB, Lakhani SR, Tan PH. Phyllodes tumour evidence gaps mapped from the 5th edition of the WHO classification of tumours of the breast. Histopathology. 2023 Apr;82(5):704-712. doi: 10.1111/his.14856. Epub 2023 Jan 30.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2024
• Primary Completion (Actual): January 2, 2025
• Study Completion (Actual): January 2, 2025

Study Registration Dates

• First Submitted: January 10, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Breast Diseases; Sarcoma; Neoplasms, Connective and Soft Tissue; Breast Neoplasms; Phyllodes Tumor
• Other Study ID Numbers: SYSKY-2024-1127-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: no plan to make individual participant data available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No