Single-fraction APBI for Early-stage Breast Cancer With Favorable Histological Subtypes (Breast-1F)

IRCCS San Raffaele311 enrolled

Overview

This is a prospective, randomized, monocentric, non-inferiority interventional clinical study comparing an Accelerated Partial Breast Irradiation (APBI) for the surgical bed of early-stage breast cancer patients with favorable histological subtypes, using stereotactic radiotherapy in a single dose of 15.5 Gy with Simultaneous Integrated Boost (SIB) to 21 Gy (study treatment, delivered in a single fraction) versus multifractionated radiotherapy of 30 Gy in 5 fractions (standard treatment, delivered in 5 fractions).

The project refers to a study on patients with early-stage breast cancer with pathological Tumor stage (pT) from in situ (pTis) to pT2 up to 3 cm in diameter, and pathological/clinical nodal stage p/cN0, and favorable histology (Luminal A and Luminal B human epidermal growth factor receptor 2 (HER2)-negative subtypes), comparing an APBI treatment delivered with stereotactic radiotherapy to the Planning Target Volume (PTV) of the tumor bed of the breast with a total dose (TD) of 15.5 Gy in one fraction, with simultaneous integrated boost (SIB) to a TD of 21 Gy to the Gross Tumor Volume (GTV) represented by tumor bed, versus 30 Gy in 5 consecutive fractions to the PTV of the tumor bed, according to the standard APBI protocol of the department (Florence protocol).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

311

Conditions

Breast Cancer

Eligibility

Sex: FEMALEMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Histological diagnosis of breast cancer 2. Patients aged ≥40 years 3. Signed informed consent 4. Stage pTis-T2, up to 3 cm in the greatest diameter 5. Luminal A and Luminal B HER2-negative histological subtypes 6. Negative surgical margins (≥ 0.2 cm) 7. Negative lymph nodes at sentinel lymph node biopsy, or alternatively with imaging tests (Positron Emission Tomography (PET)/Computed Tomography (CT) and/or axillary ultrasound, and/or breast Magnetic Resonance Imaging (MRI) with and without contrast), or, in rare cases, where still performed, with axillary dissection 8. Clinical M0 (PET/CT and/or bone scintigraphy and/or abdomen-pelvis CT with and without contrast in suspected patients), within the previous 3 months. 9. Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) ≤2 10. No prior thoracic radiotherapy 11. Fertile women using contraception methods initiated during oncological treatment. Exclusion Criteria: 1. Patients aged \< 40 years 2. Tumors \> 3 cm 3. Multicentric tumors 4. Positive or close surgical margins (\<0.2 cm) 5. Lobular carcinoma 6. Negative hormone receptors 7. HER2-positive 8. BReast CAncer (BRCA) genes BRCA1 and/or BRCA2 positive (only if known) 9. Severe systemic diseases 10. Psychiatric or other disorders that may prevent the patient from signing informed consent 11. Previous invasive cancer, except for skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the oral cavity or bladder) 12. Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome) 13. Lymph node disease (N1) 14. Evidence of distant metastasis (M1) 15. Contraindication to systemic treatment 16. Pregnant women 17. Non-compliance with the dose limits established in the treatment plan

Outcomes

Primary Outcomes

Ipsilateral Breast Tumor Recurrence (IBTR)

To demonstrate the non-inferiority of local control (ipsilateral breast tumor recurrence - IBTR) of the study treatment (delivered in a single-fraction APBI) compared to the department's standard APBI treatment (delivered in 5 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 Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) scale with 4 grades, from 0 no change to 4, worst toxicity

Time frame: 1 month

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: 3 months

Late toxicity

Late toxicity evaluated with RTOG/EORTC and 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

Local Relapse-Free Survival (LRFS)

Time to local recurrence

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

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 120 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 120 patients

Time frame: 42 months

Local relapse interim analysis

An interim analysis of local relapse rate will be performed for the first 120 patients

Time frame: 42 months

Single-fraction APBI for Early-stage Breast Cancer With Favorable Histological Subtypes (Breast-1F)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts