Accelerated Partial Breast Irradiation Using Intensity Modulated Radiotherapy Versus Whole Breast Irradiation

Phase 3

Completed

Conditions: Breast Cancer

Interventions: Radiation: Accelerated partial breast irradiation (APBI)
Radiation: Whole breast irradiation (WBI)

Registration Number: NCT02104895

Lead Sponsor: Azienda Ospedaliero-Universitaria Careggi

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%).

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 520

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Partial breast irradiation (APBI)	Accelerated partial breast irradiation (APBI)	Accelerated partial breast irradiation (APBI)
Whole breast irradiation (WBI)	Whole breast irradiation (WBI)	Conventional whole breast irradiation (WBI)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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