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

Summary

Title:

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

Conditions

• Local Neoplasm Recurrence
• Toxicity

Interventions

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). WBRT * 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

Sponsors & Collaborators

• LKH Klagenfurt

  collaborator OTHER

• Poznan University of Medical Sciences

  collaborator OTHER

• San Filippo Neri General Hospital

  collaborator OTHER

• Avera McKennan Hospital & University Health Center

  collaborator OTHER

• St. Luke's Hospital ,Cedar Rapids, US

  collaborator UNKNOWN

• A.O.U. San Giovanni Battista di Torino, Italy

  collaborator OTHER

• IRCCS Cancer Referral Center of Basilicata

  collaborator OTHER

• Heinrich-Heine University, Duesseldorf

  collaborator OTHER

• St. Elisabeth-Hospital Köln-Hohenlind, Germany

  collaborator UNKNOWN

• S.C. Radiotherapia Aziendale Umbria, Italy

  collaborator OTHER

• Azienda Ospedaliero, Universitaria Ospedali Riuniti

  collaborator OTHER

• Fondazione Salvatore Maugeri

  collaborator OTHER

• Marien Hospital Düsseldorf

  collaborator OTHER

• Azienda Ospedaliero Universitaria Maggiore della Carita

  collaborator OTHER

• Philipps University Marburg

  collaborator OTHER

• Istituti Tumori Giovanni Paolo II

  collaborator NETWORK

• University Hospital of Ferrara

  collaborator OTHER

• Paracelsus Medical University

  lead OTHER

Principal Investigators

• Gerd Fastner, Assoc.Prof. · Dep. of Radiotherapy and Radio-Oncology, Paracelsus Medical University Salzburg

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

35 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-01-31

Primary Completion

2022-12-31

Completion

2022-12-31

Countries

• Austria

Study Locations