Breast Cancer
Conditions
Keywords
Breast Cancer, Whole Breast Irradiation, Simultaneous Integrated Boost, Adjuvant Radiotherapy, Utrahypofractionated Radiotherapy, Moderately Hypofractionated Radiotherapy
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.
Interventions
RADIATIONAdjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed
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.
Sponsors
IRCCS San Raffaele
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A total of 458 patients are expected to be enrolled in this prospective, randomized study. A power of 80% and a significance level α of 5% are used to calculate the sample size. The hypothesis is that the proportion of patients free from local recurrence 5 years after the end of treatment is not less than 95.4%, with a margin of 5%. A total of 218 patients per arm are needed, and an additional 5% (22 patients) to compensate for dropouts.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Late toxicity | 5 years | Late skin toxicity evaluated with RTOG/EORTC scale, with 4 grades, from 0 = no change, to 4 = maximum toxicity |
| 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 |
| 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 |
| 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 |
| 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 | 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 RTOG/EORTC scale with 4 grades, from 0 no change to 4, worst toxicity |
| 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 |
| Local relapse interim analysis | 42 months | An interim analysis of local relapse rate 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 |
| Modeling of organ movement | 15 days | Modeling of organ movement during treatment |
| 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. |
| 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 |
| 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. |
| 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 |
Countries
Italy
Contacts
Primary ContactAndrei Fodor, MD
Backup ContactRoberta Tummineri, MD
Outcome results
None listed