Accelerated Partial Breast Irradiation With 3D-CRT and IMRT (APERT)

Accelerated Partial Breast Irradiation After Breast Conserving Surgery for Low-risk Invasive Breast Cancer: 3D Conformal Radiotherapy (3D-CRT) and Intensity Modulated Radiotherapy (IMRT) - Prospective Phase II Study

The purpose of this study is to determine in a phase II clinical trial whether accelerated partial breast irradiation after breast conserving surgery using 3 dimensional external beam radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) for low-risk invasive breast cancer patients is safe without causing serious late radiation side-effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Radiation Toxicity; Side Effects
• Intervention / Treatment: Radiation: accelerated partial breast irradiation

Detailed Description

It is a sequential phase II trial. Eligible patients after breast conserving surgery (BCS) are treated with accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT) for the first 45 patients or intensity modulated radiotherapy (IMRT) for the second 45 patients.

Primary end-point of the study: late radiation side-effects at 5 years. Early stopping criteria: Not used as primary end-point is late side-effects. Interim analysis: Not planned Secondary end-points: cosmetic results, quality of life, local recurrence-free survival, regional recurrence free survival, distant metastasis free survival, relapse free survival, overall survival, cancer specific survival.

Null-hypothesis for primary end-point: The incidence of severe (>G2) late radiation side-effects after APBI using 3D-CRT or IMRT will not exceed 10%.

Stratification:

• by treatment delivery: 3D-CRT - first 45 patients; IMRT - second 45 patients
• by bra capsize: Capsize A-B; C; and D-D+

Treatment intervention: 9 x 4.1 Gy APBI using 3D-CRT (first 45 patients) or IMRT (second 45 patients) delivered within 5 days, using twice-a-day fractionation.

Clinical target volume (CTV) and Planning target volume (PTV) definition:

CTV = excision cavity + 20 mm minus the actual pathological surgical margin in mm PTV = CTV + 5 mm in each direction

Follow-up:

• ECOG PS, physical examination (inspection and palpation), registration of side-effects (RTOG (Radiation Therapy Oncology Group) EORTC (European Organization for Research and Treatment of Cancer)) early and late radiation morbidity scoring scheme) and cosmetic results (using the Harvard scale) : 7-14 days after RT, than in every 3 months for 2 years, and every 6 months for 5 years.
• Mammography: at 6, 12, 18, 24 months, and annually thereafter
• Quality of life questionnaire (QLQ) (e.g. EORTC (European Organization for Research and Treatment of Cancer) QLQ-30 and Breast (BR)-23) before RT, at 7-14 days after RT, at 3, 6, and 12 months, and annually thereafter
• digital photography: before treatment, at 7-14 days after treatment, and yearly thereafter

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, H-1122
    • National Institute of Oncology

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:

• previous breast conserving surgery within 12 weeks (in case of adjuvant chemotherapy within 28 days after completion of chemotherapy)
• patient age > 40 years
• ECOG performance status: 0-1
• life expectancy >5 years
• invasive ductal, papillary, mucinous, medullary or tubular carcinoma
• unifocal tumor
• pathological tumor size < or = 30 mm
• pathological negative axillary nodal status with axillary dissection or sentinel lymph node biopsy
• surgical clips in the tumor bed
• pathological surgical free margins of at least 2 mm
• written informed consent of patients

Exclusion Criteria:

• Stage III-IV
• multifocal tumor
• extensive intraductal component (EIC)
• ductal or lobular carcinoma in situ (DCIS or LCIS)
• invasive lobular cancer (ILC)
• lymph-vascular invasion (LVI)
• contralateral breast cancer
• history of treatment for previous breast cancer
• lactation or breast feeding women
• Paget-disease of the nipple
• psychiatric disorder
• increased radiosensitivity (e.g. collagen vascular disease)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Accelerated partial breast irradiation; Accelerated partial breast irradiation delivered by 3 dimensional conformal radiotherapy or intensity modulated radiotherapy	Radiation: accelerated partial breast irradiation; 9 x 4.1 Gy accelerated partial breast irradiation delivered by 3D-CRT or IMRT over 5 consecutive days, using twice-a-day fractionation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
late radiation side-effect	Late radiation side-effects at 5 years scored by the RTOG (Radiation Therapy Oncology Group) EORTC (European Organization for Research and Treatment of Cancer) late radiation morbidity scoring scheme	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cosmetic results	cosmetic results at 5 years measured by the Harvard criteria	5 years
local tumor control	Local tumor control defined as reappearance of the tumor in the ipsilateral breast	5 years
regional tumor control	regional tumor control at 5 years	5 years
overall survival	overall survival at 5 years	5 years
disease free survival	disease free survival at 5 years	5 years
cancer specific survival	cancer specific survival at 5 years	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
quality of life	quality of life measured by the EORTC (European Organization for Research and Treatment of Cancer) QLQ-30 and BR-23 questionnaires	5 years

Collaborators and Investigators

• Sponsor: National Institute of Oncology, Hungary
• Investigators: Study Chair: Csaba Polgár, MD, PhD, MSc, National Institute of Oncology; Principal Investigator: Norbert Mészáros, MD, National Institute of Oncology

Publications and helpful links

General Publications

• Mozsa E, Meszaros N, Major T, Frohlich G, Stelczer G, Sulyok Z, Fodor J, Polgar C. Accelerated partial breast irradiation with external beam three-dimensional conformal radiotherapy. Five-year results of a prospective phase II clinical study. Strahlenther Onkol. 2014 May;190(5):444-50. doi: 10.1007/s00066-014-0633-1. Epub 2014 Mar 12.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: December 2, 2013
• First Submitted That Met QC Criteria: December 2, 2013
• First Posted (Estimate): December 6, 2013

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: August 12, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: breast cancer; intensity modulated radiotherapy; accelerated partial breast irradiation; breast conserving therapy; 3D conformal radiotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NIO-APERT_01