Abstract OT1-4-01: HIOB trial - Hypofractionated whole-breast irradiation preceded by intraoperative radiotherapy with electrons as anticipated boost
Authors: Reitsamer Roland , Fastner Gerd , Kopp Michael , Sedlmayer Felix 
Published: May 2015

ClinicalTrials.gov Identifier: NCT01343459

Brief background discussion:

The commonly accepted standard fractionation schedule for whole breast irradiation (WBI) consists of 25fractionations with single fractional doses of 2 Gy, resulting in cumulative doses of 50 Gy to the whole breast. Hypofractionation trials from UK and Canada demonstrated a similar outcome in local control and cosmesis compared to conventional fractionation. The combination of IOERT boost and hypofractionation was not yet evaluated.

Trial design:

Prospective one-armed multi-center trial - ISIORT 01

Eligible patients are treated with hypofractionated whole breast irradiation (WBI) of 40.5 Gy in 2.7 Gy per fraction for 15 days, preceded by an intraoperative electron boost (IOERT) to the tumor bed of 10 Gy (90% isodose) during breast conserving surgery.

Eligibility criteria:

Inclusion criteria:

Invasive breast cancer

Age 35 years and older

T1/T2, N1/N2, G1 - G3

Hormone receptor and Her 2 status: no limitations

Exclusion criteria:

Non-invasive breast cancer

Age less than 35 years

T3/T4, N2/N3

Neoadjuvant chemotherapy

Aim of the study:

To assess the effectiveness of IOERT in combination with hypofractionated WBI in terms of in-breast tumor control and cosmetic outcome, by matching or exceeding the best published results for annual LR rates in 3 different age groups in reference to an upper limit (exceeding = inferiority) and a lower limit (undershooting = superiority) which were estimated on the basis of the existing literature as follows:

Age 35 – 40 years:

Upper limit (best published evidence): 1.2 % (EORTC 22881- Boost trial)

Lower limit (commonly expected dimension): 0.72 % (CONSORT trial)

Age 41 – 50 years:

Upper limit (best published evidence): 1.2 % (EORTC 22881- Boost trial)

Lower limit (commonly expected dimension): 0.72 % (CONSORT trial)

Age over 50 years:

Upper limit (best published evidence): 0.7 % (EORTC 22881- Boost trial)

Lower limit (commonly expected dimension): 0.4 % (START B trial)

Primary endpoint:

Proof of superiority or iso-effectiveness.

Secondary endpoints:

Acute toxicity (CTC- toxicity scoring system) and late toxicity (LENT SOMA scoring system), cosmetic results (Van Limbergen - Score), DFS, OS.

Statistical methods:

Sequential Probability Ratio Test (SPRT):

As a consequence of best published analyses for this patient selection, stopping rules for annual local recurrence rates are defined as follows:

Age group 35-40: H0: p1 &lt;= 0.72% vs H1: p1 &gt; 0.72% with p2 = 4.0%

Age group 41-50: H0: p1 &lt;= 0.72% vs H1: p1 &gt; 0.72% with p2 = 2.4%

Age group 51+: H0: p1 &lt;= 0.4% vs H1: p1 &gt; 0.4% with p2 = 1.4%

H0-Hypothesis means no superiority to standard regimen.

H1-Hypothesis means superiority of HIOB against best published evidence.

Present accrual and target accrual:

Start date: January 2011

Estimated enrollment: 1500 patients

542 patients recruited by March 2014

10 international institutions recruiting.

Citation Format: Roland Reitsamer, Gerd Fastner, Michael Kopp, Felix Sedlmayer. HIOB trial - Hypofractionated whole-breast irradiation preceded by intraoperative radiotherapy with electrons as anticipated boost [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-4-01.