Neoadjuvant Radiation in Locally Advanced Breast Cancer

Effect of Neoadjuvant Radiation and Prediction of Response to Treatment in Locally Advanced Breast Cancer

The purpose of this study is to evaluate the efficacy and safety of neoadjuvant radiation therapy in improving local-regional control and facilitating surgical conversion in patients with inoperable locally advanced breast cancer after 2-6 courses of neoadjuvant chemotherapy. This study will also investigate whether beta-alanine supplementation and spatially fractionated radiotherapy can enhance the therapeutic response to neoadjuvant chemoradiotherapy. In addition, this study aims to explore tumor microenvironmental features and molecular biomarkers associated with treatment response, radioresistance, immune activation, and long-term outcomes.

Study Overview

• Status: Recruiting
• Conditions: Breast Neoplasms
• Intervention / Treatment: Radiation: Neoadjuvant radiotherapy; Dietary supplement: β-alanine; Radiation: Spatially fractionated radiotherapy

Detailed Description

RATIONALE:

The optimal management of patients with locally advanced breast cancer(LABC) remains unknown. Neoadjuvant chemotherapy is currently accepted as a standard treatment strategy for patients with inoperable LABC; however, a substantial proportion of patients do not achieve sufficient tumor regression and may remain unsuitable for surgery. For these patients, radiation therapy before surgery may provide an opportunity for further tumor downstaging, improve the chance of surgical conversion, and enhance local-regional control.

OUTLINE:

This is a prospective, open-label, multi-arm phase II study. Eligible patients are women with inoperable locally advanced breast cancer who remain unsuitable for surgery following 2-6 courses of neoadjuvant chemotherapy.

Patients will receive one of the following treatment strategies: neoadjuvant radiation therapy, beta-alanine supplementation plus neoadjuvant radiation therapy, or spatially fractionated radiotherapy.

The primary objective of this study is to evaluate the clinical efficacy of these radiation-based strategies, including local-regional control and surgical conversion. Secondary objectives include treatment safety, tumor response, pathological response when surgery is performed, and long-term clinical outcomes.

This study will also investigate early predictors of treatment response. Fresh tumor tissue and peripheral blood samples will be collected and stored before treatment for biomarker analysis. Molecular and tumor microenvironmental characteristics associated with radiotherapy sensitivity, radioresistance, immune activation, and treatment outcomes will be explored. Imaging assessments will be performed before and after treatment, and ultrasound-based parameters, including shear wave elastography, will be evaluated as potential early imaging predictors of treatment response.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoli Yu; Phone Number: +86-021-64175590; Email: xiaoliyu@fudan.edu.cn
• Study Contact Backup: Name: Jin Meng; Phone Number: +86 18121299532; Email: jinmeng@fudan.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Xiaoli Yu; Email: xiaoliyu@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced breast carcinoma
• Inoperable with with 4-6 courses of prior chemotherapy
• No contradiction of radiation or chemo-radiotherapy
• Patients should have the ability to understand and the willingness to sign a written informed consent document
• Signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

• Other prior or concurrent malignancy except adequately treated squamous cell or basal cell skin cancer or contralateral breast DCIS
• Coagulation disorders
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia
• Serious underlying medical illness with life expectancy less than 2 years.
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant radiotherapy	Radiation: Neoadjuvant radiotherapy; The preoperative radiation dose will be 50 Gy in 25 fractions to the breast and regional lymph node PTV, followed by surgical evaluation. Operable patients will proceed to surgery; inoperable patients will continue radiotherapy to 60 Gy in 30 fractions, with residual breast and nodal lesions boosted to 66 Gy in 33 fractions.
Experimental: β-alanine plus neoadjuvant radiotherapy	Radiation: Neoadjuvant radiotherapy; The preoperative radiation dose will be 50 Gy in 25 fractions to the breast and regional lymph node PTV, followed by surgical evaluation. Operable patients will proceed to surgery; inoperable patients will continue radiotherapy to 60 Gy in 30 fractions, with residual breast and nodal lesions boosted to 66 Gy in 33 fractions.; Dietary supplement: β-alanine; β-alanine, 1.7g, tid, p.o
Experimental: Spatially fractionated radiotherapy	Radiation: Spatially fractionated radiotherapy; Spatially fractionated radiotherapy will be delivered as a lattice radiotherapy boost. The high-dose gross tumor volume (GTV) will receive 15 Gy in 1 fraction. The conventional clinical target volume (CTV), including the ipsilateral breast and regional lymphatic drainage area, will receive 40.05 Gy in 15 fractions. The boost volume, if applicable, including positive lymphatic drainage areas, will receive an additional 10 Gy in 5 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response rate	only for operable patients	1 year
Fbjective response rate(ORR)	for inoperable patients	3 year
Event free survival(EFS)	for all patients	3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression	including local-regional recurrence, disease-free survival, overall survival	3 year
Radiation Toxicity	using CTCAE 4.0 and RTOG classification	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biologic predictor for treatment response	biopsies of the original tumor before treatment for future molecular biology studies in LABC	before treatment
The role of ultrasound in predicting treatment response	shear wave elastography(SWE) technology	before and 1 month after treatment

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Xiaoli Yu, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): December 25, 2023
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; biomarkers; neoadjuvant radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Therapeutics; Combined Modality Therapy; Neoadjuvant Therapy
• Other Study ID Numbers: FDRT-BC016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No