Breast Cancer
Conditions
Keywords
Breast Cancer, Accelerated Partial Breast Irradiation, Adjuvant Radiotherapy, Stereotactic Body Radiotherapy, Simultaneous Integrated Boost, Ultrahypofractionated Radiotherapy
Brief summary
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).
Detailed description
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).
Interventions
RADIATIONAdjuvant single-fraction accelerated partial breast irradiation
Experimental arm (arm 1-single-fraction APBI) patients will be treated to a total dose (TD) of 15.5 Gy to the PTV with a simultaneous integrated boost (SIB) to a TD of 21 Gy to the tumor bed, while arm 2-five-fractions APBI patients with 30 Gy/ 5 fractions to PTV.
Sponsors
IRCCS San Raffaele
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A total of 311 patients are expected to be enrolled in this prospective randomized study. For the sample size calculation, a 90% power and a significance level α = 5% are set. The hypothesis is that the proportion of patients free from Ipsilateral Breast Tumor Recurrence (IBTR) 5 years after the end of treatment will be no less than 97.8%, with a margin of 5%. A total of 148 patients per arm are required, with an additional 5% (15 patients) to compensate for drop-outs.
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ipsilateral Breast Tumor Recurrence (IBTR) | 5 years | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 120 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 120 patients |
| Local relapse interim analysis | 42 months | An interim analysis of local relapse rate will be performed for the first 120 patients |
| Acute toxicity | 1 month | 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 |
| Late toxicity | 5 years | 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 |
| Local Control | 5 years | Local control of the treated site expressed in terms of local recurrence rate |
| Local Relapse-Free Survival (LRFS) | From the date of radiotherapy end until the date of local relapse, assessed up to 5 years | Time to local recurrence |
| 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 |
| 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 |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Radiomics | 5 years | Evaluation of radiomic characteristics: Mathematical extraction of the spatial distribution of signal intensities and pixel interrelationships of medical images of the patients, to quantify textural information resampled according to International Biomarker Standardization Initiative (IBSI). |
| Predictive factors for toxicity, disease progression and death | 5 years | Identification of clinical, imaging, and laboratory prognostic factors for an aggressive phenotype of Luminal A and Luminal B HER2-negative breast cancer and for toxicity |
| Modeling of organ movement | 5 days | Modeling of organ movement during treatment |
| 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 |
Countries
Italy
Contacts
Primary ContactAndrei Fodor, MD
Backup ContactNadia G Di Muzio, Prof
Outcome results
None listed