Adjuvant Whole Breast Radiotherapy (RT) With Intensity Modulated Radiotherapy (IMRT) and a Simultaneous Integrated Boost Versus Conventional RT and a Sequential Boost (IMRT-MC2)

Randomized Phase III Trial Comparing Intensity Modulated Radiotherapy With Integrated Boost to Conventional Radiotherapy With Consecutive Boost in Patients With Breast Cancer After Breast Conserving Surgery

The IMRT-MC2 study is a prospective, two armed, multicenter, randomized phase-III-trial comparing intensity modulated radiotherapy with integrated boost to conventional radiotherapy with consecutive boost in patients with breast cancer after breast conserving surgery. 502 patients will be recruited and randomized in two arms: patients in arm A will receive IMRT in 28 fractions delivering 50.4 Gy to the breast and 64.4 Gy to the tumor-bed by an integrated boost, while patients in arm B will receive conventional radiotherapy of the breast in 28 fractions to a dose of 50.4 Gy and a consecutive boost in 8 fractions to a total dose of 66.4 Gy. Primary aim of the study is the assessment of the cosmetic outcome and local control after breast radiotherapy. The study hypothesis is that intensity modulated radiotherapy (IMRT) is, in spite of the reduced treatment duration, at least equivalent to conventional therapy.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: IMRT with an simultaneous integrated boost

• Study Type: Interventional
• Enrollment (Anticipated): 502
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Holger Hof, MD; Phone Number: +496221568202; Email: holger.hof@med.uni-heidelberg.de
• Study Contact Backup: Name: Vasileios Askoxylakis, MD; Phone Number: +496221568202; Email: vasileios.askoxylakis@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69115
    • Recruiting
    • University of Heidelberg, Dept. Radiation Oncology
    • Principal Investigator: Juergen Debus, MD, PhD
    • Contact: Holger Hof, MD; Phone Number: +496221568202; Email: holger.hof@med.uni-heidelberg.de
    • Contact: Vasileios Askoxylakis, MD; Phone Number: +496221568202; Email: vasileios.askoxylakis@med.uni-heidelberg.de
    • Sub-Investigator: Holger Hof, MD
    • Sub-Investigator: Vasileios Askoxylakis, MD
    • Sub-Investigator: Leonie Fetzner, MD
    • Sub-Investigator: Jörg Heil, MD
    • Sub-Investigator: Alexandra Jensen, MD
  • Mannheim, Germany, 68135
    • Not yet recruiting
    • University of Heidelberg, Dept. Radiation Oncology
    • Contact: Frederik Wenz, MD; Phone Number: +496213833530; Email: frederik.wenz@medma.uni-heidelberg.de
    • Principal Investigator: Frederik Wenz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All patients aged >18 years and < 70 years after breast conserving surgery.

• Patients aged ≥ 70 years with following risk factors:

  • Tumor stadium ≥ T2
  • Multifocal disease
  • Lymphangiosis
  • Extended intraductal component
  • Resection margin ≤3mm

Exclusion Criteria:

• Refusal of the patients to be included in the study
• Karnofsky Performance Score ≤ 70%
• Metastatic disease (M1)
• Other malignancies
• Previous radiotherapy of the breast
• Pregnancy

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: IMRT + integrated boost; 28 fractions delivering 50.4 Gy to the whole breast and 64.4 Gy to the tumor-bed by an integrated boost	Radiation: IMRT with an simultaneous integrated boost; IMRT in 28 fractions delivering 50.4 Gy to the whole breast and 64.4 Gy to the tumor-bed
Other: Conventional RT + sequential boost; Conventional radiotherapy of the whole breast in 28 fractions to a dose of 50.4 Gy and a consecutive boost in 8 fractions to a total dose of 66.4 Gy	Radiation: IMRT with an simultaneous integrated boost; IMRT in 28 fractions delivering 50.4 Gy to the whole breast and 64.4 Gy to the tumor-bed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cosmetic results	The cosmetic outcome will be assessed by two independent investigators using the Harvard criteria (excellent, good, fair, poor). Additional parameters to be evaluated are skin color, teleangiectasy, scars, shrinking and asymmetry. Evaluation will also be carried out using a quantitative digitizer scoring system based on standardized photodocumentations of the breast, as described by Vrieling et al.. by calculation of a breast retraction assessment (BRA) score.	2 years
local recurrence rates		5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fraction of patients surviving (overall survival)	ratio of number of patients alive to total number of patients treated	15 years
fraction of patients surviving without tumor recurrence (disease-free survival)	ratio of patients alive without tumor recurrence to total number of patients treated	15 years
quality of life	EORTC questionnaires QLQ-C30 and QLQ-BR23	2 years
occurence of secondary malignancies	ratio of patients with occurence of secondary malignancies to total number of patients treated	15 years

Collaborators and Investigators

• Sponsor: Heidelberg University
• Collaborators: DLR German Aerospace Center
• Investigators: Principal Investigator: Juergen Debus, MD, PhD, Heidelberg University

Publications and helpful links

General Publications

• Forster T, Hommertgen A, Häfner MF, Arians N, König L, Harrabi SB, Schlampp I, Köhler C, Meixner E, Heinrich V, Weidner N, Hüsing J, Sohn C, Heil J, Golatta M, Hof H, Krug D, Debus J, Hörner-Rieber J. Quality of life after simultaneously integrated boost with intensity-modulated versus conventional radiotherapy with sequential boost for adjuvant treatment of breast cancer: 2-year results of the multicenter randomized IMRT-MC2 trial. Radiother Oncol. 2021 Oct;163:165-176. doi: 10.1016/j.radonc.2021.08.019. Epub 2021 Sep 1.
• Horner-Rieber J, Forster T, Hommertgen A, Haefner MF, Arians N, Konig L, Harrabi SB, Schlampp I, Weykamp F, Lischalk JW, Heinrich V, Weidner N, Husing J, Sohn C, Heil J, Hof H, Krug D, Debus J. Intensity Modulated Radiation Therapy (IMRT) With Simultaneously Integrated Boost Shortens Treatment Time and Is Noninferior to Conventional Radiation Therapy Followed by Sequential Boost in Adjuvant Breast Cancer Treatment: Results of a Large Randomized Phase III Trial (IMRT-MC2 Trial). Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1311-1324. doi: 10.1016/j.ijrobp.2020.12.005. Epub 2020 Dec 13.
• Krug D, Koder C, Hafner MF, Arians N, Harrabi SB, Koerber SA, Forster T, Schlampp I, Sohn C, Heil J, Hof H, Horner-Rieber J, Debus J. Acute toxicity of normofractionated intensity modulated radiotherapy with simultaneous integrated boost compared to three-dimensional conformal radiotherapy with sequential boost in the adjuvant treatment of breast cancer. Radiat Oncol. 2020 Oct 13;15(1):235. doi: 10.1186/s13014-020-01652-x.
• Askoxylakis V, Jensen AD, Hafner MF, Fetzner L, Sterzing F, Heil J, Sohn C, Husing J, Tiefenbacher U, Wenz F, Debus J, Hof H. Simultaneous integrated boost for adjuvant treatment of breast cancer--intensity modulated vs. conventional radiotherapy: the IMRT-MC2 trial. BMC Cancer. 2011 Jun 15;11:249. doi: 10.1186/1471-2407-11-249.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): March 1, 2013
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: March 24, 2011
• First Submitted That Met QC Criteria: March 24, 2011
• First Posted (Estimate): March 25, 2011

Study Record Updates

• Last Update Posted (Estimate): April 7, 2011
• Last Update Submitted That Met QC Criteria: April 6, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: breast cancer; IMRT; breast conserving surgery; Integrated boost; adjuvant radiotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IMRT-MC2