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

N/ARecruitingNCT07020780

IRCCS San Raffaele458 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

458

Conditions

Breast Cancer

Interventions

Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bedRADIATION

Experimental arm (arm 1-five fractions WBI) patients will be treated to a total dose (TD) of 26 Gy in 5 fractions to whole breast, and a simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed, while arm 2-fifteen-fractions WBI patients with 40 Gy/15 fractions to PTV, and 48 Gy SIB to the tumor bed.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (1)

IRCCS San Raffaele Scientific Institute

Milan, Italy

RECRUITING

Outcomes

Primary Outcomes

Local Relapse Free Survival (LRFS)

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).

Time frame: 5 years

Secondary Outcomes

Acute toxicity

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

Time frame: 1 month

Acute toxicity

Time frame: 3 months

Late toxicity

Late skin toxicity evaluated with RTOG/EORTC scale, with 4 grades, from 0 = no change, to 4 = maximum toxicity

Time frame: 5 years

Late toxicity

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

Time frame: 5 years

Local Control

Local control of the treated site expressed in terms of local recurrence rate

Time frame: 5 years

Ipsilateral Breast Tumor Recurrence (IBTR)

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).

Central Contacts

Andrei Fodor, MD

CONTACT

+390226437634 fodor.andrei@hsr.it

Roberta Tummineri, MD

CONTACT

+390226435452 tummineri.roberta@hsr.it

Data from ClinicalTrials.gov

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Regional Relapse-Free Survival (RRFS)

Time to regional (nodal) recurrence

Time frame: From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years

Distant Metastasis-Free Survival (DMFS)

Time to distant (metastatic) relapse

Time frame: From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years

Disease-Free Survival (DFS)

Time to first any relapse: local, regional or distant

Time frame: From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years

Breast Cancer Specific Survival (BCSS)

Time until death from breast cancer

Time frame: From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years

Overall Survival (OS)

Time until death from any cause

Time frame: From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years

Cosmesis

Cosmetic results evaluated with Harvard scale. It assesses the global esthetic appearance of the breast, categorized as Excellent, Good, Fair, or Poor

Time frame: 5 years

Acute toxicity interim analysis

An interim analysis of acute toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 200 patients

Time frame: 3 months

Late toxicity interim analysis

An interim analysis of late toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 200 patients

Time frame: 42 months

Local relapse interim analysis

An interim analysis of local relapse rate will be performed for the first 200 patients

Time frame: 42 months

Incidence of Treatment-Emergent Adverse Events as assessed with breast tumor specific quality of life questionnaires

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

Time frame: 5 years

Modeling of organ movement

Modeling of organ movement during treatment

Time frame: 15 days

Radiomics

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.

Time frame: 5 years

Predictive factors for toxicity

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

Time frame: 5 years

Predictive factors for disease progression

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

Time frame: 5 years

Predictive factors for death

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.

Time frame: 5 years