Intraoperative Boost Radiotherapy With Electrons (IOERT) Followed By Hypofractionated Whole-Breast Irradiation (WBRT)

Study Overview
=================
Brief Summary
-----------------
Hypofractionated intraoperative boost (HIOB) is defined as hypofractionated WBRT (40.5 Gy in 2.7 Gy per fraction) preceded by an intraoperative boost to the tumor bed (10 Gy IOERT). The HIOB study concept will test whether such a combined schedule is superior or iso-effective standard RT in terms of local control and cosmetic outcome.

Detailed Description
-----------------
The purpose of this research study is to find out the effects (good and bad) of adding a dose of radiation to the area of the cancer during surgery to whole breast radiation therapy (WBRT) after surgery. IOERT is the application of electron radiation directly to the residual tumor or tumor bed during cancer surgery. WBRT is a type of radiation therapy used to treat patients who have cancer in the breast covering the entire breast tissue. Both immediate and long-term effects will be measured. For patients with certain types of breast cancer, one standard treatment is removal of the area of cancer and a small amount of normal tissue around it followed by breast radiation. The radiation treatment in this situation usually lasts 3 to 5 1/2 weeks of WBRT followed by 5-8 daily radiation treatments at the site where the lump was removed called a boost. During this study, the single dose of electron irradiation (IOERT) given at the surgical site during the operation will replace the usual 5-8 days of localized radiation and the whole breast radiation will last 3 weeks.

Official Title
-----------------
Intraoperative Boost Radiotherapy With Electrons (IOERT) Followed By Hypofractionated Whole-Breast Irradiation (WBRT)

Conditions
-----------------
Invasive Lobular and Ductal Carcinoma

Intervention / Treatment
-----------------
* Radiation: Hypofractionated Whole Breast Radiation Therapy
* Radiation: Intraoperative Electron Radiation Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histological proven invasive breast carcinoma (ductal and lobular) Age > 40 years Karnofsky performance status >70% Single discrete tumor or focal microcalcifications that can be imaged on a specimen radiograph or multifocal disease within the same quadrant with a maximum dimension of 4 cm (invasive foci) Nodal Status: NO-1 Clear surgical margins: R0; min 2mm. Re-excision after IOERT is permitted but not required to achieve (-) margin. All grades G1 - G3 Any hormonal receptor and Her-2 status Informed consent Exclusion Criteria: In-situ Carcinoma without invasive component or multifocal disease > 4 cm Tumor stage: T3 or 4 Nodal Status > N1 pathologically Surgical margins < 2mm Multicentricity Previous radiotherapy to the involved breast Karnofsky Index < 70% Mixed connective tissue diseases e.g. rheumatoid polyarthritis, thromboangitis obliterans, systemic lupus. Distant metastases Unable to provide written consent

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraoperative Electron Radiation Therapy<br>A single dose of electron irradiation given at the surgical site during the operation to remove the cancerous tumor will replace the usual 5-8 days of localized radiation. Hypofractionated Whole Breast Radiation Therapy must start within 14-56 days post operatively. | Radiation: Hypofractionated Whole Breast Radiation Therapy<br>* Hypofractionated Whole Breast Radiation Therapy must start within 14-56 days postoperatively (week 2-8 post-op) Single reference dose per fraction: 2.7 Gy (ICRU) Number of fractions: 15 Number of fractions per week: 5 Regular Radiation Therapy breaks: Weekend/ Holidays (not exceeding 7 days break) Total dose: 50.5 Gy (40.5 WBRT + 10 Gy boost) Radiation: Intraoperative Electron Radiation Therapy<br>Radiation: Intraoperative Electron Radiation Therapy<br>* Intraoperative Electron Radiation Therapy (IOERT) is delivered after completion of the lumpectomy and sentinel node procedure. IOERT is performed on mobile or fixed linac with variable electron energies in the range of 4-12 MeV<br>* Other names: Mobetron;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of acute and late toxicity | Assessment of acute toxicity of breast irradiation according to CTC-toxicity Scoring - systems: At the end of Radiation Therapy At time of first follow-up investigation (week 8 - 10) Assessment of late toxicity according to NSABP scoring - systems at 6, 12, 24, 36, 48, and 60 months | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cosmetic Evaluation | Assessment of cosmetic outcome according to 5-point scoring system Before Whole Breast Radiation Therapy Not earlier than 7 months after Whole Breast Radiation Therapy At yearly follow-up (photodocumentation in standardized positions) for 5 years. | 5 years | 
| Disease Free Survival | Recurrence assessments as documented at post-op follow-ups per protcol. | 5 years | 
| Overall Survival | The length of time from the start of treatment to death within the 5 year period. | 5 Years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast cancer, Radiation therapy, Mobetron, IOERT, IORT, Hypofractionated radiation therapy, Partial breast radiation