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

Randomised Phase 3 Trial Of Accelerated Partial Breast Irradiation Using Intensity Modulated Radiotherapy Versus Whole Breast Irradiation

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Whole breast irradiation (WBI); Radiation: Accelerated partial breast irradiation (APBI)

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%).

• Study Type: Interventional
• Enrollment (Actual): 520
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Whole breast irradiation (WBI); Conventional whole breast irradiation (WBI)	Radiation: Whole breast irradiation (WBI); Conventional whole breast irradiation (WBI)
Experimental: Partial breast irradiation (APBI); Accelerated partial breast irradiation (APBI)	Radiation: Accelerated partial breast irradiation (APBI); Accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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"	5-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	5 years
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	5 years

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi
• Investigators: Principal Investigator: Lorenzo Livi, Full Prof, Florence University; Principal Investigator: Icro Meattini, M.D., Azienda Ospedaliero-Universitaria Careggi

Publications and helpful links

General Publications

• Livi L, Buonamici FB, Simontacchi G, Scotti V, Fambrini M, Compagnucci A, Paiar F, Scoccianti S, Pallotta S, Detti B, Agresti B, Talamonti C, Mangoni M, Bianchi S, Cataliotti L, Marrazzo L, Bucciolini M, Biti G. Accelerated partial breast irradiation with IMRT: new technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):509-15. doi: 10.1016/j.ijrobp.2009.04.070. Epub 2009 Aug 21.
• Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, Paiar F, Scotti V, De Luca Cardillo C, Bastiani P, Orzalesi L, Casella D, Sanchez L, Nori J, Fambrini M, Bianchi S. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015 Mar;51(4):451-463. doi: 10.1016/j.ejca.2014.12.013. Epub 2015 Jan 17.
• Meattini I, Saieva C, Marrazzo L, Di Brina L, Pallotta S, Mangoni M, Meacci F, Bendinelli B, Francolini G, Desideri I, De Luca Cardillo C, Scotti V, Furfaro IF, Rossi F, Greto D, Bonomo P, Casella D, Bernini M, Sanchez L, Orzalesi L, Simoncini R, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial. Breast Cancer Res Treat. 2015 Oct;153(3):539-47. doi: 10.1007/s10549-015-3565-2. Epub 2015 Sep 9.
• Meattini I, Marrazzo L, Saieva C, Desideri I, Scotti V, Simontacchi G, Bonomo P, Greto D, Mangoni M, Scoccianti S, Lucidi S, Paoletti L, Fambrini M, Bernini M, Sanchez L, Orzalesi L, Nori J, Bianchi S, Pallotta S, Livi L. Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial. J Clin Oncol. 2020 Dec 10;38(35):4175-4183. doi: 10.1200/JCO.20.00650. Epub 2020 Aug 24.
• Becherini C, Meattini I, Livi L, Garlatti P, Desideri I, Scotti V, Orzalesi L, Sanchez LJ, Bernini M, Casella D, Nesi S, Nori J, Bianchi S, Pallotta S, Marrazzo L. External accelerated partial breast irradiation for ductal carcinoma in situ: long-term follow-up from a phase 3 randomized trial. Tumori. 2019 Jun;105(3):205-209. doi: 10.1177/0300891618811278. Epub 2018 Nov 26.
• Meattini I, Saieva C, Miccinesi G, Desideri I, Francolini G, Scotti V, Marrazzo L, Pallotta S, Meacci F, Muntoni C, Bendinelli B, Sanchez LJ, Bernini M, Orzalesi L, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: Health-related quality of life final analysis from the Florence phase 3 trial. Eur J Cancer. 2017 May;76:17-26. doi: 10.1016/j.ejca.2017.01.023. Epub 2017 Mar 3.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 4, 2014
• First Posted (Estimate): April 7, 2014

Study Record Updates

• Last Update Posted (Estimate): August 11, 2016
• Last Update Submitted That Met QC Criteria: July 11, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Breast cancer; Intensity modulated radiotherapy; Early breast cancer; Adjuvant breast cancer; Accelerated partial breast irradiation
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: APBI-IMRT-Florence

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided