Hypofractionated Loco-regional Adjuvant Radiation Therapy of Breast Cancer Combined With a Simultaneous Integrated Boost

The Skagen Trial 1, Moderately Hypofractionated Loco-regional Adjuvant Radiation Therapy of Early Breast Cancer Combined With a Simultaneous Integrated Boost: a Randomised Clinically Controlled Trial

The purpose of the study is to investigate the difference in late radiation morbidity between hypofractionated and normofractionated loco-regional breast irradiation irrespective of mastectomy or lumpectomy. In patients who a candidates for a boost, the boost will be provided as a simultaneous integrated boost.

Study Overview

• Status: Active, not recruiting
• Conditions: Fibrosis; Lymphedema
• Intervention / Treatment: Radiation: Loco-regional RT

Detailed Description

The randomization is between 50 Gy / 25 fractions and 40 Gy/15 fractions, 5 fractions weekly. In patients treated with boost 2 dose levels are accepted: 16 Gy/8 fractions and 10 Gy/5 fractions. These boost treatments will be provided as simultaneous integrated boost, where the overall treatment time in general is shortened 5 days. Thus the dose levels for boost patients are:

63 Gy / 51.52 Gy / 28 fractions, 57 Gy / 50 Gy / 25 fractions, 52.2 Gy / 42.3 Gy / 18 fractions, and 45.75 Gy / 40 Gy / 15 fractions.

The primary endpoint is arm lymphedema 3 years after radiation therapy, but other late radiation morbidities will also be evaluated along with recurrence and sites of recurrence. Follow up of morbidity will continue for 10 years.

The hypothesis is that women operated for early breast cancer with indication for loco-regional radiation therapy can be offered moderately hypofractionated therapy without developing more late radiation induced morbidity compared to normofractionated radiation therapy.

• Study Type: Interventional
• Enrollment (Actual): 2963
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Operated for early node-positive breast cancer with indication for loco-regional breast radiotherapy

Exclusion Criteria:

Previous radiotherapy to chest wall, pregnant/lactating, comorbidity which may hinder 10 years follow up

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: Hypofractionated loco-regional RT; 40 Gy / 15 fractions, 2.67 Gy per fraction, 5 fractions weekly	Radiation: Loco-regional RT
Active Comparator: Normofractionated loco-regional RT; 50 Gy / 25 fractions, 2.00 Gy per fraction, 5 fractions weekly	Radiation: Loco-regional RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of ipsilateral arm lymphedema	>=10% increased arm circumference compared to the other arm defines edema	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrosis grade 2-3	Breast or chest wall induration	3 years
Arm range of motion	Impaired shoulder movement is present when >20 degrees difference between arms at flexion and/or abduction	3 years
Development of dyspigmentation	Grade 2 or worse dyspigmentation compared to baseline	3 years
Recurrence	Any recurrence location and time to event	10 years
Development of pain in the irradiated area	Pain in the irradiated area measured on visual analog scale compared to baseline	3 years
Change in sensibility	Change in sensibility in the irradiated area compared to baseline measured as yes/no	3 years
Development of edema on breast / chest wall	Grade 2 or worse edema	3 years
Development of telangiectasia in irradiated area	Grade 2 or worse telangiectasia	3 years

Collaborators and Investigators

• Sponsor: Danish Breast Cancer Cooperative Group
• Collaborators: Danish Cancer Society
• Investigators: Study Chair: Troels Bechmann, MD,PhD, Vejle Hospital; Study Chair: Mette Nielsen, MD, Odense University Hospital; Principal Investigator: Birgitte Offersen, MD, Aarhus University Hospital; Study Chair: Hanne Nielsen, MD, Aarhus University Hospital; Study Chair: Claus Kamby, MD, Rigshospitalet, Denmark; Study Chair: Sami Al-Rawi, MD, Naestved Hospital; Study Chair: Mechthild Krause, MD, Technische Universität Dresden Klinik und Poliklinik für Strahlentherapie und Radioonkologie; Study Chair: Andreas Schreiber, MD, Praxis für Strahlentherapie, Dresden; Study Chair: Ingvil Mjaaland, MD, Stavanger hospital; Study Chair: Tanja Marinko, MD, Institute of Oncology Ljubljana; Study Chair: Carine Kirkove, MD, Radiotherapy Department Université Catholique de Louvain, Cliniques Universitaires St-Luc, Brussels; Study Chair: Egil Blix, MD, University Hospital of North Norway, Tromsoe; Study Chair: Unn-Miriam Kasti, Kristiansand Hospital, Norway

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): July 1, 2021
• Study Completion (Anticipated): July 1, 2032

Study Registration Dates

• First Submitted: February 19, 2015
• First Submitted That Met QC Criteria: March 4, 2015
• First Posted (Estimate): March 10, 2015

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Radiation induced morbidity, recurrence
• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphedema
• Other Study ID Numbers: The Skagen Trial 1