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.
BACKGROUND
In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results.


METHODS
We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519.


RESULTS
Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1.44% (95% CI 0.51-2.38) with APBI and 0.92% (0.12-1.73) with whole-breast irradiation (difference 0.52%, 95% CI -0.72 to 1.75; p=0.42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0.08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46).


CONCLUSIONS
The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival.


BACKGROUND
German Cancer Aid.
Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany. Electronic address: vratislav.strnad@uk-erlangen.de.
Vratislav
V
Strnad
Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
Oliver J
OJ
Ott
Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany; Department of Radiation Oncology, University Hospital Rostock, Rostock, Germany.
Guido
G
Hildebrandt
Department of Radiation Oncology, University Hospital AKH Wien, Vienna, Austria.
Daniela
D
Kauer-Dorner
Department of Radiation Oncology, University Hospital Rostock, Rostock, Germany.
Hellen
H
Knauerhase
Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary.
Tibor
T
Major
Brachytherapy Department, Centrum Onkologii-Instytut im Marii Skłodowskej, Warsaw, Poland; Podkarpacki Hospital Cancer Center Brzozów, Brzozów, Poland.
Jaroslaw
J
Lyczek
Department of Radiation Oncology, Valencian Institute of Oncology, Valencia, Spain.
Jose Luis
JL
Guinot
Department of Radiation Oncology, University Hospital Kiel, Germany.
Jürgen
J
Dunst
Department of Radiation Oncology, Catalan Institute of Oncology, Barcelona, Spain.
Cristina
C
Gutierrez Miguelez
Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Pavel
P
Slampa
Department of Radiation Oncology, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany.
Michael
M
Allgäuer
Department of Radiation Oncology, University Hospital Bern, Inselspital, Bern, Switzerland.
Kristina
K
Lössl
Department of Radiation Oncology, University Hospital Würzburg, Würzburg, Germany.
Bülent
B
Polat
Interdisciplinary Brachytherapy Unit, University of Lübeck/UKSH Campus Lübeck, Lübeck, Germany.
György
G
Kovács
Department of Radiation Oncology, Clemens Hospital, Münster, Germany.
Arnt-René
AR
Fischedick
Department of Radiation Oncology, University Hospital Jena, Jena, Germany.
Thomas G
TG
Wendt
Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany; Department of Radiation Oncology, University Hospital Rostock, Rostock, Germany.
Rainer
R
Fietkau
Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany.
Marion
M
Hindemith
Department of Radiation Oncology, University Hospital AKH Wien, Vienna, Austria.
Alexandra
A
Resch
Brachytherapy Department, Centrum Onkologii-Instytut im Marii Skłodowskej, Warsaw, Poland.
Anna
A
Kulik
Department of Radiation Oncology, Valencian Institute of Oncology, Valencia, Spain.
Leo
L
Arribas
Department of Radiation Oncology, University Hospital Kiel, Germany; Department of Radiotherapy, Municipal Hospital Cologne, University Witten-Herdecke, Witten, Germany.
Peter
P
Niehoff
Department of Radiation Oncology, Catalan Institute of Oncology, Barcelona, Spain.
Fernando
F
Guedea
Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany.
Annika
A
Schlamann
Department of Radiation Oncology, University Hospital AKH Wien, Vienna, Austria.
Richard
R
Pötter
Department of Medical Informatics, Biometry and Epidemiology, University Erlangen-Nuremberg, Erlangen, Germany.
Christine
C
Gall
Department of Medical Informatics, Biometry and Epidemiology, University Erlangen-Nuremberg, Erlangen, Germany.
Martina
M
Malzer
Department of Medical Informatics, Biometry and Epidemiology, University Erlangen-Nuremberg, Erlangen, Germany.
Wolfgang
W
Uter
Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary.
Csaba
C
Polgár
D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000379:methods*; D001943:Breast Neoplasms / Q000532:radiotherapy* / Q000601:surgery / Q000628:therapy; D002278:Carcinoma in Situ / Q000532:radiotherapy* / Q000601:surgery / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000532:radiotherapy* / Q000601:surgery / Q000628:therapy; D002408:Catheters, Indwelling; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental / Q000379:methods; D008875:Middle Aged; D011879:Radiotherapy Dosage; D016896:Treatment Outcome