Radiotherapy (RT) is a fundamental pillar in the fight against cancer. In the case of breast cancer, RT has traditionally been applied as an adjuvant treatment following surgery. However, in recent years, there has been research into the potential benefit of administering RT prior to surgery in a neoadjuvant manner. Given that these studies have shown promising results, it is logical to think that certain patients could benefit from exclusive RT treatment, thereby avoiding surgery and its possible sequelae. This study is a phase I dose-escalation clinical trial with sequential assignment, open-label, in which five different doses (20Gy, 23Gy, 26Gy, 28Gy, and 30Gy) will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique. The aim of the study is to determine the maximum tolerated dose (MTD) based on acute toxicity, which will allow us to proceed with a phase II clinical trial to confirm efficacy and assess the late toxicity of the treatment. Secondary objectives include assessing the pathological response via core needle biopsy (CNB), radiological response, quality of life, and cosmesis. Additionally, molecular studies will be conducted on tissue and through liquid biopsy; pre- and post-treatment, we aim to identify mutations and predictors of response.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
20Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
23Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
26Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
28Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
30Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
Hospital Universitario Son Espases
Palma, Balearic Islands, Spain
Establish the single-fraction radiation dose (MTD)
To establish the single-fraction SBRT radiation dose (MTD) that causes an incidence of dose-limiting toxicities (DLTs) lower than 33%
Time frame: 3 months
Chronic toxicity
Assessed at 6 and 12 months post-treatment using CTCAE v5.0 criteria for skin, fatigue, and breast.
Time frame: 1 year
Radiological response to treatment
Measured with MRI or contrast mammography 12 months post-RT using RECIST criteria.
Time frame: 1 year
Pathological response to treatment
Between 1 and 3 core needle biopsies (CNB) will be performed, guided by ultrasound on the treated lesion at 6 and 12 months post-RT to establish the rate of residual tumor cells scored by pathology review of H\&E slides.
Time frame: 1 year
Patient-reported quality of life
Measured using the EORTC QLQ-C30 questionnaires before RT and at 3 and 12 months post-treatment. EORTC QLQ-C30- scale goes from 1/not at all to 4/very much. There is additionally a rate of overall health and quality of life that is a scale from 1 to 7.
Time frame: 1 year
Cosmesis after treatment
Measured using the Modified Harvard-Harris Cosmetic Scale (MHHCS) at 1, 3, 6, and 12 months post-treatment. Photographs of the breasts will be taken before treatment and at each follow-up visit, to be evaluated later using an external validation system. The MHCCS scale compares baseline images with those obtained post-treatment, allowing the assessment of cosmesis as follows: Poor, fair, good or excellent.
Time frame: 1 year
Tumor DNA sequencing
Tumor biopsies will be taken before and at 6 and 12 months post-treatment. Next Generation Sequencing (NGS) will be performed to characterize radiation-induced changes in tumor DNA.
Time frame: 1 year
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