Breast Cancer
Conditions
Keywords
Breast cancer, Early breast cancer, Adjuvant breast cancer, Accelerated partial breast irradiation, Intensity modulated radiotherapy
Brief summary
The aim of this Phase 3 randomised trial is to compare the efficacy and safety of whole breast radiotherapy to accelerated partial breast irradiation using intensity-modulated radiotherapy technique in selected early breast cancer patients after breast conserving surgery.
Detailed description
The surgeons were requested to place clips at the borders of the surgical bed, using a minimum of four clips. The presence of surgical clips was a selection criterion to avoid geographic misses. Computed tomography (CT) scanning was performed using 0.3-cm thick-slices and a slice spacing of 0.3 cm. In patients assigned to APBI arm, the clinical target volume (CTV) was drawn with a uniform 1-cm three-dimensional margin around the surgical clips. The CTV was limited to 3 mm from the skin surface and 3 mm from the lung-chest wall interface. A second uniform, three-dimensional 1-cm margin was added to the CTV to obtain the planning target volume (PTV). The PTV was allowed to extend 4 mm inside the ipsilateral lung and was limited to 3 mm from the skin. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. No respiratory control was used. Concerning the experimental Arm (accelerated partial breast irradiation), a dose of 30 Gy in five fractions at 6 Gy/fraction was prescribed. The following constraints were adopted for plan optimization: PTV coverage: 100% of PTV covered by 95% of the prescribed dose (V28.5 = 100%); maximal dose to PTV \<105% (31.5 Gy); minimal dose to PTV 28 Gy; uninvolved breast (i.e., ipsilateral breast without PTV): not \>50% covered by a dose of \>50% of the prescribed dose (V15 \<50%); ipsilateral lung: not \>20% covered by a dose \>10 Gy (V10\<20%); contralateral lung: not \>10% covered by a dose \>5 Gy (V5\<10%); contralateral breast: maximal dose \<1 Gy; heart: not \>10% covered by a dose \>3 Gy (V3 \<10%).
Interventions
Accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT)
RADIATIONWhole breast irradiation (WBI)
Conventional whole breast irradiation (WBI)
Sponsors
Azienda Ospedaliero-Universitaria Careggi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age at presentation \>40 y * Tumor size \<25 mm * Wide excision or quadrantectomy with clear margins (\>5 mm) * Clips placed in tumor bed * Full informed consent from patient
Exclusion criteria
* Cardiac dysfunction * Forced expiratory volume in 1 second (FEV1) \<1 L/m * Extensive intraductal carcinoma * Multifocal cancer * Psychiatric problems * Recurrent breast cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ipsilateral Breast Tumor Recurrence | 5-year | We defined local relapse (true recurrence) as the reappearance of the breast cancer in the index quadrant and ipsilateral breast tumours as any new breast cancer diagnosed in other quadrants of the same breast. The sum of local relapses and new ipsilateral breast tumours was defined as the ipsilateral breast tumour recurrence (IBTR). Locoregional tumour recurrence also included any recurrence in the ipsilateral axillary, supraclavicular, or internal mammary chain nodal regions.here we report the percentage of participants in each arm who experienced Ipsilateral Breast Tumor Recurrence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Skin Toxicity | 5 years | Acute skin toxicity ≥ grade 2, here we report the percentage of participants in each arm who experienced Acute skin toxicity ≥ grade 2 |
| Excellent Cosmesis | 5 years | Physician-rated cosmesis, Cosmetic outcome was scored on the four-category Harvard Breast Cosmesis Scale. An excellent cosmetic result score was assigned when the treated breast looked like the contralateral one; a good cosmetic score was assigned for minimal but identifiable radiation effects of the treated breast; a fair score was used if significant radiation effects were readily observable; a poor score was used for severe sequelae due to radiation effects |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Whole Breast Irradiation (WBI) Conventional whole breast irradiation (WBI)
Whole breast irradiation (WBI): Conventional whole breast irradiation (WBI) | 260 |
| Partial Breast Irradiation (APBI) Accelerated partial breast irradiation (APBI)
Accelerated partial breast irradiation (APBI): Accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT) | 260 |
| Total | 520 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 14 |
Baseline characteristics
| Characteristic | Whole Breast Irradiation (WBI) | Partial Breast Irradiation (APBI) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 102 Participants | 118 Participants | 220 Participants |
| Age, Categorical Between 18 and 65 years | 158 Participants | 142 Participants | 300 Participants |
| Region of Enrollment Italy | 260 participants | 260 participants | 520 participants |
| Sex: Female, Male Female | 260 Participants | 260 Participants | 520 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 173 / 260 | 49 / 246 |
| serious Total, serious adverse events | 0 / 260 | 0 / 246 |
Outcome results
Primary
Ipsilateral Breast Tumor Recurrence
We defined local relapse (true recurrence) as the reappearance of the breast cancer in the index quadrant and ipsilateral breast tumours as any new breast cancer diagnosed in other quadrants of the same breast. The sum of local relapses and new ipsilateral breast tumours was defined as the ipsilateral breast tumour recurrence (IBTR). Locoregional tumour recurrence also included any recurrence in the ipsilateral axillary, supraclavicular, or internal mammary chain nodal regions.here we report the percentage of participants in each arm who experienced Ipsilateral Breast Tumor Recurrence
Time frame: 5-year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Whole Breast Irradiation (WBI) | Ipsilateral Breast Tumor Recurrence | 1.4 percentage of participants |
| Partial Breast Irradiation (APBI) | Ipsilateral Breast Tumor Recurrence | 1.5 percentage of participants |
Secondary
Acute Skin Toxicity
Acute skin toxicity ≥ grade 2, here we report the percentage of participants in each arm who experienced Acute skin toxicity ≥ grade 2
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Whole Breast Irradiation (WBI) | Acute Skin Toxicity | 37.7 percentage of participants |
| Partial Breast Irradiation (APBI) | Acute Skin Toxicity | 2 percentage of participants |
Secondary
Excellent Cosmesis
Physician-rated cosmesis, Cosmetic outcome was scored on the four-category Harvard Breast Cosmesis Scale. An excellent cosmetic result score was assigned when the treated breast looked like the contralateral one; a good cosmetic score was assigned for minimal but identifiable radiation effects of the treated breast; a fair score was used if significant radiation effects were readily observable; a poor score was used for severe sequelae due to radiation effects
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Whole Breast Irradiation (WBI) | Excellent Cosmesis | 89.6 percentage of participants |
| Partial Breast Irradiation (APBI) | Excellent Cosmesis | 95.1 percentage of participants |