5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer

• Registration Number: NCT07020780
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

This is a prospective, randomized, single-center, non-inferiority interventional clinical trial comparing whole breast irradiation (WBI) to a total dose of 26 Gy in 5 fractions with simultaneous integrated boost (SIB) to the tumor bed to a total dose of 30 Gy, and WBI to a total dose of 40.05 Gy in 15 fractions with SIB to the tumor bed to a total dose of 48 Gy (standard treatment), for young or unfavorable breast cancer patients.

Detailed Description

The project refers to a study on patients with T1-T3 Nx-N3 breast cancer, aged under 40 years or with unfavorable histology (lobular carcinoma, multifocal tumor, or histological subtypes Luminal B Her2 positive, Hormonal Receptors negative Her 2 positive, Triple Negative Breast Cancer-TNBC-) treated with breast-conserving surgery (BCS) and radiotherapy to the whole breast (+/- lymph node areas) to a total dose of 26 Gy in 5 fractions, with simultaneous boost (SIB) to the tumor bed to the total dose of 30 Gy, that will be compared with the current departmental standard of moderately hypofractionated radiotherapy to the whole breast, to 40.05 Gy in 15 fractions, with SIB to the tumor bed to a total dose of 48 Gy.

Study Timeline

• Study First Submitted: 2025-05-27
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-05
• Last Update Submitted: 2025-06-05
• Study First Posted: 2025-06-13
• Last Update Posted: 2025-06-13
• Study Start: 2025-07-01
• Primary Completion: 2029-06-30
• Study Completion: 2035-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 458

Inclusion Criteria

1. Histological diagnosis of breast cancer
2. Patients younger than 40 years regardless of histological subtype, or patients between 40 and 70 years with lobular carcinoma, histological subtypes Luminal B Her2 positive, or with hormone receptors negative and Her2 positive (ErbB2), or triple negative (TNBC)
3. Signed informed consent
4. Clinical stage T1-T3, Nx-N3
5. Negative surgical margins (≥ 0.2 cm)
6. Clinical M0 in the previous 3 months
7. PS (ECOG) ≤2
8. No previous thoracic radiotherapy
9. Fertile women using contraceptive methods started during oncological treatment

Exclusion Criteria

1. Patients with favorable characteristics (Luminal A, Luminal B Her2 negative, ≥ 40 years) undergoing partial irradiation
2. Patients who have undergone mastectomy
3. Multicentric tumors
4. Positive or close surgical margins (<0.2 cm)
5. BRCA1/2 positive (only if known)
6. Serious systemic diseases
7. Mental or other disorders that may prevent the patient from signing the informed consent
8. Previous invasive tumor, except skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (for example carcinoma in situ of the oral cavity or bladder)
9. Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
10. Evidence of distant metastases (M1)
11. Contraindication to treatment systemic
12. Pregnant women
13. Non-compliance with the dose limits established in the treatment plan

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Local Relapse Free Survival (LRFS)	5 years	o demonstrate the non-inferiority of local control (local relapse free survival - LRFS) of the study treatment (delivered in five fractions) compared to the department's standard WBI treatment (delivered in 15 fractions).

Secondary Outcome Measures

Name	Time	Method
Local relapse interim analysis	42 months	An interim analysis of local relapse rate will be performed for the first 200 patients
Modeling of organ movement	15 days	Modeling of organ movement during treatment
Cosmesis	5 years	Cosmetic results evaluated with Harvard scale. It assesses the global esthetic appearance of the breast, categorized as Excellent, Good, Fair, or Poor
Overall Survival (OS)	From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years	Time until death from any cause
Acute toxicity	3 months	Acute toxicity grade ≥3 as the maximum toxicity value within 1 month and 3 months after the completion of radiotherapy treatment evaluated with RTOG/EORTC scale with 4 grades, from 0 no change to 4, worst toxicity
Late toxicity	5 years	Late toxicity evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale, with 5 grades, from 0 = no change, to 5 = death for toxicity
Local Control	5 years	Local control of the treated site expressed in terms of local recurrence rate
Ipsilateral Breast Tumor Recurrence (IBTR)	5 years	Ipsilateral breast tumor recurrence - IBTR- of the study treatment (delivered in 5 fractions WBI+SIB) compared to the department's standard WBI+SIB treatment (delivered in 15 fractions).
Regional Relapse-Free Survival (RRFS)	From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years	Time to regional (nodal) recurrence
Distant Metastasis-Free Survival (DMFS)	From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years	Time to distant (metastatic) relapse
Disease-Free Survival (DFS)	From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years	Time to first any relapse: local, regional or distant
Breast Cancer Specific Survival (BCSS)	From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years	Time until death from breast cancer
Radiomics	5 years	CT radiomic features predicting relapse or death will be extracted, acording to IBSI (Image Biomarker Standardisation Initiative), owning to the different families of features: Morphology, Statistical, Intensity Histogram, Grey Level Cooccurrence Matrix 3D-average, Grey Level Co-occurrence Matrix 3D-combined, Grey Level Run Lenght 3D-average. Grey Level Run Lenght 3D_combined, Grey Level Size Zone Matrix 3D, Neighbors Grey Tone Difference Matrix 3D, Grey Level Distance Zone Matrix 3D, standard convolutional filters within radiomic workflow (wavelets, Laplacian of Gaussian). Area Under Curve (AUC) will be taken as representative of the discriminative power for each of the significant RF.
Acute toxicity interim analysis	3 months	An interim analysis of acute toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 200 patients
Late toxicity interim analysis	42 months	An interim analysis of late toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 200 patients
Incidence of Treatment-Emergent Adverse Events as assessed with breast tumor specific quality of life questionnaires	5 years	Survey with the questionnaire of European Organisation for Research and Treatment of Cancer (EORTC) Quality of life of brain tumor patients (EORTC QLQ BR42) which contains 42 questions on patients' quality of life with answers from 1, lowest grade, to 4, highest grade
Predictive factors for disease progression	5 years	Identification of clinical, imaging, and laboratory prognostic factors for an aggressive phenotype of breast cancer. Univariable and multivariable analysis will be performed to identify factors associated with disease progression
Predictive factors for death	5 years	Identification of clinical, imaging, and laboratory prognostic factors for an aggressive phenotype of breast cancer. Univariable and multivariable Cox analysis will be performed to identify factors associated with death.
Predictive factors for toxicity	5 years	Identification of clinical, imaging, and laboratory prognostic factors for toxicity. Univariable and multivariable Cox analysis will be performed to identify factors associated with \>/= G2 toxicity

Trial Locations

Locations (1)

IRCCS San Raffaele Scientific Institute; 🇮🇹 Milan, Italy