Breast Neoplasms
Conditions
Keywords
breast cancer, neoadjuvant radiotherapy, biomarkers
Brief summary
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.
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.
Interventions
RADIATIONNeoadjuvant 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_SUPPLEMENTβ-alanine
β-alanine, 1.7g, tid, p.o
RADIATIONSpatially 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.
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological response rate | 1 year | only for operable patients |
| Fbjective response rate(ORR) | 3 year | for inoperable patients |
| Event free survival(EFS) | 3 year | for all patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression | 3 year | including local-regional recurrence, disease-free survival, overall survival |
| Radiation Toxicity | 6 months | using CTCAE 4.0 and RTOG classification |
Countries
China
Contacts
CONTACTXiaoli Yu
CONTACTJin Meng
PRINCIPAL_INVESTIGATORXiaoli Yu
Fudan University
Outcome results
None listed