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Intra-Operative Electron Boost and Hypofractionated Whole-Breast Irradiation During Breast-conserving Treatment (BCT) (HIOB)

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ClinicalTrials.gov Identifier: NCT01343459
Recruitment Status : Recruiting
First Posted : April 28, 2011
Last Update Posted : January 9, 2018
Information provided by (Responsible Party):

Study Description
Brief Summary:


HIOB - Hypofractionated Whole-Breast Irradiation preceded by Intraoperative Radiotherapy with Electrons as anticipated Boost ISIORT- 01

HIOB is defined as hypofractionated WBRT (40,5 Gy in 2,7 Gy per fraction) preceded by an Intraoperative Boost to the tumor bed ( 90 % reference dose of 10 Gy, 11,1 Gy Dmax IOERT).

Primary endpoint is the proof of superiority of a new treatment regimen.

The HIOB study concept is supposed to test the hypothesis whether such a combined schedule is superior (or iso-effective) towards "standard" RT in terms of local control and cosmetic outcome.

In the vast majority of all publications, annual and 5 year in-breast recurrence rates following BCT showed a clear dependency on patient age within the following boundaries (primary references):

Age > 50: Bartelink (standard): 0,7% (annual) 3,5% (5y) START B (best): 0,4 %(annual) 2,0% (5y)

Age 41-50: Bartelink (standard) 1,2% (annual) 6,0% (5y) Whelan (best) 0,72%(annual) 3,6% (5y)

Age ≥ 35-40 Bartelink (standard) 2% (annual) 10% (5y) Whelan (best) 0,72% (annual) 3,6% (5y)

long these three different age groups, benchmarking will be performed against the best published results following `Golden Standard`RT, usually defined as conventionally fractionated WBRT with 50 Gy (25 x2) plus external tumor bed boost with 10-16 Gy electrons (5-8x2Gy).

Superiority is defined as going below the lower limit of the estimated 5 year local recurrence rate within the respective age group Inferiority is defined as crossing the respective upper limit .

Secondary endpoint:

Disease free survival

Tertiary endpoint: toxicity assessment (acute and late) including long term cosmetic evaluation

Study design and statistics:

  • Prospective multicenter single-armed
  • Sequential probability ratio test (SPRT)
  • Separate analysis within three different age groups

Estimated Accrual time: strongly dependent on recruitment per year within the respective age group . Due to the statistical estimation of Szenario A and B the study will close after max. Time-period of 10 years in case of A or 6,4 years in case of B..

Principal investigators and study coordinators:

UC of Radiotherapy and Radio-Oncology UC of Special Gynecology and Breast Cancer Center Landeskrankenhaus Salzburg, Paracelsus University Clinics

Condition or disease Intervention/treatment
Local Neoplasm Recurrence Toxicity Radiation: HIOB

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1300 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hypofractionated Whole-Breast Irradiation Preceded by Intra-Operative Radiotherapy With Electrons as Anticipated Boost HIOB A New Option in Breast-Conserving Treatment for Operated Breast Cancer Stages I and II
Study Start Date : January 2011
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: IOERT followed by hypofractionated WBRT
HIOB: IOERT of 11.1 Gy followed by WBRT with 15 times 2.7 Gy per fraction.
Radiation: HIOB

IOERT single shot as a boost followed by hypofractionated WBRT (HIOB)

  • IOERT is performed on mobile or fixed linacs
  • Reference dose: 11 Gy specified as maximum dose, with a minimum target volume dose of 90% encompassing the PTV (i.e. 10 Gy).


  • must start within day 36- 56 postoperatively (week 6 - 8 p.o.) in case of adjuvant hormonal treatment (or no further tumor specific medication)
  • In case of adjuvant chemotherapy, a time - gap between IOERT and WBRT up to 9 months is allowed.
  • Single reference dose per fraction: 2,7 Gy (ICRU)
  • Number of fractions: 15, Number of fractions per week: 5
  • Total WBRT dose: 40,5 Gy

Outcome Measures

Primary Outcome Measures :
  1. 5 year local recurrence rate: Sequential Probability Ratio Test [ Time Frame: 10 years ]
    Sequential Probability Ratio Test

Secondary Outcome Measures :
  1. Acute toxicity: CTC-toxicity Scoring-system;Late toxicity: LENT-SOMA scoring-systems [ Time Frame: 10 years ]
    CTC-toxicity Scoring-System;LENT-SOMA scoring-systems

Other Outcome Measures:
  1. Cosmesis [ Time Frame: 10 years ]
    van Limbergen Scoring System

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological proven invasive breast carcinoma
  • Age: ≥ 35 years
  • Tumor stage T1-2
  • nodal status: N0-1
  • Freedom of surgical margins: R0 (both invasive and in situ component), that means no ink on tumors (invasive or in situ) (ago-online.de) .
  • Also multifocal disease within the same quadrant with a maximum distance of < 5 cm
  • all grades G1-G3
  • Hormonal receptor and Her-2 status: no limitations
  • Informed and undersigned consent

Exclusion Criteria:

  • In-situ Carcinoma without invasive component
  • Age < 35
  • Tumor stage T3,4
  • Nodal status >N1
  • if irradiation of regional lymphatics is required
  • R1
  • Re-excision after IOERT
  • Immediately secondary mastectomy (not due to recurrence).
  • Multicentricity according to international definition: > 5 cm distance to each other
  • previous radiotherapy to the involved breast
  • Karnofsky Index < 70%
  • Mixed connective tissue diseases including rheumatoid Polyarthritis, Thrombangitis obliterans
  • Chronic pre-existent lung disease (Lung fibrosis, Pneumokoniosis, late-type Allergies like Farmer lung; Asthma bronchiale, severe Emphysema, COPD III *)
  • Cardiac Co-Morbidity: clinically positive coronary vessel disease, St.p. myocardial infarction, pacemakers and/or defibrillators)
  • Distant metastases
  • breast size (PTV) > 2500 ml
  • missing written consent
  • observed pregnancy
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01343459

Contact: Felix Sedlmayer, Prof. MD 0043/662/4482/3915 f.sedlmayer@salk.at
Contact: Gerd Fastner, MD 0043/662/4482/58918 g.fastner@salk.at

Paracelsus private university; University Clinic of Radio-Oncology Recruiting
Salzburg, Austria, 5020
Contact: Felix Sedlmayer, Prof. MD    0043/662/4482/3915    f.sedlmayer@salk.at   
Contact: Gerd Fastner, MD    0043/662/4482/58918    g.fastner@salk.at   
Principal Investigator: Felix Sedlmayer, Prof. MD         
Sponsors and Collaborators
Paracelsus Medical University
LKH Klagenfurt
Poznan University of Medical Sciences
San Filippo Neri General Hospital
Avera McKennan Hospital & University Health Center
St. Luke’s Hospital ,Cedar Rapids, US
A.O.U. San Giovanni Battista di Torino, Italy
IRCCS Cancer Referral Center of Basilicata
Heinrich-Heine University, Duesseldorf
St. Elisabeth-Hospital Köln-Hohenlind, Germany
S.C. Radiotherapia Aziendale Umbria, Italy
Azienda Ospedaliero, Universitaria Ospedali Riuniti
Fondazione Salvatore Maugeri
Marien Hospital Düsseldorf, Germany
Azienda Ospedaliero Universitaria Maggiore della Carita
Philipps University Marburg Medical Center
Istituti Tumori Giovanni Paolo II
Principal Investigator: Felix Sedlmayer, Prof. MD Paracelsus private university; University Clinic of Radio-Oncology, Müllnerhaupstraße 48 5020 Salzburg/Austria/Europe
More Information


Responsible Party: Prof. Sedlmayer, Prof., MD, Paracelsus Medical University
ClinicalTrials.gov Identifier: NCT01343459     History of Changes
Other Study ID Numbers: ISIORT - 01
ISIORT 01 ( Other Identifier: ISIORT )
First Posted: April 28, 2011    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Prof. Sedlmayer, Paracelsus Medical University:
Hypofractionated Whole breast irradiation
Hypofractionated Whole breast irradiation long term results
Breast conserving therapy
IORT with electrons in breast cancer
IOERT as anticipated Boost
IOERT and hypofractionated whole breast irradiation

Additional relevant MeSH terms:
Neoplasm Recurrence, Local
Disease Attributes
Pathologic Processes
Neoplastic Processes