APBI Versus EBRT Therapy After Breast Conserving Surgery for Low-risk Breast Cancer

Interstitial Brachytherapy Alone Versus External Beam Radiation Therapy After Breast Conserving Surgery for Low-risk Invasive Carcinoma and Low-risk Ductal Carcinoma in Situ (DCIS) of the Female Breast

To assess the role of interstitial brachytherapy alone compared to whole breast irradiation in a defined low-risk group of invasive breast cancer or ductal carcinoma in situ concerning local failure (all ipsilateral local recurrences) to affirm the hypothesis that local control rates in each arm are equivalent.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Accelerated partial breast irradiation; Radiation: External beam whole breast irradiation

Detailed Description

To assess the role of interstitial brachytherapy alone compared to whole breast irradiation in a defined low-risk group of invasive breast cancer or ductal carcinoma in situ concerning local failure (all ipsilateral local recurrences) to affirm the hypothesis that local control rates in each arm are equivalent.

• Study Type: Interventional
• Enrollment (Actual): 1300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • University Hospital AKH Wien, Department of Radiotherapy and Radiobiology
• Germany
  • Erlangen, Germany, 91054
    • University Hospital Erlangen, Department of Radiation Oncology
  • Kiel, Germany
    • University Hospital Kiel, Department of Radiation Oncology
  • Leipzig, Germany
    • University Hospital Leipzig, Department of Radiation Oncology
  • Lübeck, Germany
    • University Hospital Lübeck, Department of Radiation Oncology
  • Regensburg, Germany
    • Hospital Barmherzige Brüder, Department of Radiation Oncology
  • Rostock, Germany
    • University Hospital Rostock, Department of Radiation Oncology
• Hungary
  • Budapest, Hungary
    • National Institute of Oncology, Department of Radiation Oncology
• Poland
  • Warszawa, Poland
    • Kierownik Zakladu Brachyterapii, Cetrum Onkologii
• Spain
  • Barcelona, Spain, 08907
    • Catalan Institut of Oncology, Department of Radiation Oncology
  • Valencia, Spain, 46009
    • Valencian Institut of Oncology, Department of Radiation Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Stage 0, I or II breast cancer.
• Invasive ductal, papillary, mucinous, tubular, medullary or lobular carcinoma.
• Ductal carcinoma in situ (DCIS) alone.
• No lymph invasion (L0) and no hemangiosis (V0).
• Lesions of > 3 cm diameter, histopathologically confirmed.
• pN0/pNmi (a minimum of 6 nodes in specimen, or a negative sentinel node is acceptable); in the case of DCIS alone axillary staging (e.g. sentinel lymph node biopsy) is optional.
• M0.
• Clear resection margins at least 2 mm in any direction; by lobular histology or DCIS histology only the resection margins must be clear at least 5 mm.
• For DCIS only: lesions must be classified as low or intermediate risk group (Van Nuys Prognostic Index <8).
• Unifocal and unicentric DCIS or breast cancer.
• Age >= 40 years.
• Time interval from final definitive breast surgical procedure to the start of external beam therapy or to brachytherapy is less than 12 weeks (84 days). If patients receive chemotherapy the radiotherapy can be started before systemic treatment (within 12 weeks). The radiation therapy can be also given in the interval between the chemotherapy courses. It is also possible to start radiation therapy after chemotherapy is completed according local protocols as soon as possible within 4 weeks after chemotherapy.
• Signed study-specific consent form prior to randomization.

Exclusion Criteria:

• Stage III or IV breast cancer.
• Surgical margins that cannot be microscopically assessed.
• Extensive intraductal component (EIC).
• Paget's disease or pathological skin involvement.
• Synchronous or previous breast cancer.
• Prior malignancy (< 5 years prior to enrollment in study) except non-melanoma skin cancer or cervical carcinoma FIGO 0 and I if patient is continuously disease-free.
• Pregnant or lactating women.
• Collagen vascular disease.
• The presence of congenital diseases with increased radiation sensitivity, for example Ataxia telangiectatica or similar.
• Psychiatric disorders.
• Patient with breast deemed technically unsatisfactory for brachytherapy.

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
Experimental: APBI; Accelerated Partial Breast Irradiation with multicatheter brachytherapy	Radiation: Accelerated partial breast irradiation; APBI with PDR and HDR brachytherapy
Active Comparator: EBRT; Standard External Beam Whole Breast Irradiation	Radiation: External beam whole breast irradiation; Standard Whole breast irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Local control	5-years, 10 ten-years

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of acute and late side effects	5-years
Differences in cosmetic results	5-years
Distant metastases free survival	5-years
Survival rates (Overall Survival, Disease-free Survival)	5-years
Contralateral breast cancer rate	5-years
Quality-of-Life	5-years

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Study Chair: Vratislav Strnad, MD, University Hospital Erlangen, Germany; Study Chair: Csaba Polgár, MD, National Institute of Oncology Budapest, Hungary; Study Director: Oliver J Ott, MD, University Hospital Erlangen, Germany

Publications and helpful links

General Publications

• Schafer R, Strnad V, Polgar C, Uter W, Hildebrandt G, Ott OJ, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Miguelez CG, Slampa P, Allgauer M, Lossl K, Kovacs G, Fischedick AR, Fietkau R, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Gall C, Polat B; Groupe Europeen de Curietherapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial. Lancet Oncol. 2018 Jun;19(6):834-844. doi: 10.1016/S1470-2045(18)30195-5. Epub 2018 Apr 22.
• Polgar C, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Miguelez CG, Slampa P, Allgauer M, Lossl K, Polat B, Kovacs G, Fischedick AR, Fietkau R, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Potter R, Gall C, Uter W, Strnad V; Groupe Europeen de Curietherapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Feb;18(2):259-268. doi: 10.1016/S1470-2045(17)30011-6. Epub 2017 Jan 14.
• Ott OJ, Strnad V, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Miguelez CG, Slampa P, Allgauer M, Lossl K, Polat B, Kovacs G, Fischedick AR, Wendt TG, Fietkau R, Kortmann RD, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Potter R, Gall C, Malzer M, Uter W, Polgar C; Groupe Europeen de Curietherapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). GEC-ESTRO multicenter phase 3-trial: Accelerated partial breast irradiation with interstitial multicatheter brachytherapy versus external beam whole breast irradiation: Early toxicity and patient compliance. Radiother Oncol. 2016 Jul;120(1):119-23. doi: 10.1016/j.radonc.2016.06.019. Epub 2016 Jul 12.
• Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Gutierrez Miguelez C, Slampa P, Allgauer M, Lossl K, Polat B, Kovacs G, Fischedick AR, Wendt TG, Fietkau R, Hindemith M, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Potter R, Gall C, Malzer M, Uter W, Polgar C; Groupe Europeen de Curietherapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016 Jan 16;387(10015):229-38. doi: 10.1016/S0140-6736(15)00471-7. Epub 2015 Oct 19.

Helpful Links

• Trial Homepage with a short version of the protocol

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): November 1, 2009
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: November 21, 2006
• First Submitted That Met QC Criteria: November 21, 2006
• First Posted (Estimate): November 22, 2006

Study Record Updates

• Last Update Posted (Estimate): May 13, 2016
• Last Update Submitted That Met QC Criteria: May 12, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: accelerated partial breast irradiation; multicatheter brachytherapy; high dose rate brachytherapy; pulsed dose rate brachytherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: GEC-ESTRO APBI Trial

Plan for Individual participant data (IPD)

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