Intra-Operative Electron Boost and Hypofractionated Whole-Breast Irradiation During Breast-conserving Treatment (BCT) (HIOB)
HIOB - Hypofractionated Whole-Breast Irradiation preceded by Intra-Operative 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 Intra-Operative 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 .
Disease free survival
Tertiary endpoint: toxicity assessment (acute and late) including long term cosmetic evaluation
Study design and statistics:
- Prospective multi-center 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
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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|
- 5 year local recurrence rate: Sequential Probability Ratio Test [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Acute toxicity: CTC-toxicity Scoring-system;Late toxicity: LENT-SOMA scoring-systems [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||May 2021|
|Estimated Primary Completion Date:||March 2021 (Final data collection date for primary outcome measure)|
|Experimental: Hypofractionated WBRT with IOERT Boost||
See Points 4.1 und 4.2 Inclusion/Exclusion criteria of the entire protocol
- Lumpectomy / segmentectomy / tumorectomy with sufficient safety margins (see above). Lymph node assessment must follow a sentinel node concept.
- Perioperative antibiotic prophylaxis is mandatory
- After IORT, radio-opaque clips have to be fixed at the tumorbed.
neoadjuvant: not allowed adjuvant: allowed.
There are no limitations towards special chemotherapeutic schemes and schedules.
- 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 6 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
RT of regional lymphatics: exclusion criterion
Diagnostics of Local recurrence:
- yearly mammographies,
- optional breast sonography, MRI
- LR has to be histologically confirmed
Follow-up screening for detection of metastases (minimum requirements):
- Chest X-Ray,
- abdominal sonography,
- lab tests incl. tumor markers.
Assessment of acute toxicity of WBRT according to CTC-toxicity Scoring-systems:
Assessment of late toxicity according to LENT-SOMA scoring-systems
Assessment of cosmetic outcome according to 5-point- Scoring System (vanLimbergen) starting before WBRT, including photodocumentation in standardized positions
|Contact: Felix Sedlmayer, Prof. MDfirstname.lastname@example.org|
|Contact: Gerd Fastner, MDemail@example.com|
|Paracelsus private university; University Clinic of Radio-Oncology||Recruiting|
|Salzburg, Austria, 5020|
|Contact: Felix Sedlmayer, chairman Prof. MD 0043/662/4482/3915 firstname.lastname@example.org|
|Contact: Gerd Fastner, MD 0043/662/4482/58918 email@example.com|
|Principal Investigator: Felix Sedlmayer, chairman Prof. MD|
|Principal Investigator:||Felix Sedlmayer, Prof. MD||Paracelsus private university; University Clinic of Radio-Oncology, Müllnerhaupstraße 48 5020 Salzburg/Austria/Europe|