Prospective Phase II Study of Intraoperative Radiotherapy (IORT) in Elderly Patients With Small Breast Cancer

Study Overview
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Brief Summary
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This prospective, multicentric single arm phase II study is based on the protocol of the international TARGIT-A study. The purpose is to investigate the efficacy of a single intraoperative radiotherapy treatment within elderly low risk patients (≥ 70 years, cT1, cN0, cM0, invasive-ductal) which is followed by WBRT only when risk factors are present. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines.

Detailed Description
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Patients ≥ 70 years with small, low-risk breast cancer who are operated but not irradiated show local relapse rates around 4% after 4 years. With adjuvant whole breast radiotherapy (WBRT) the local relapse rate drops to 1% after 4 years under Tamoxifen (Hughes et al 2004). It has been demonstrated (Polgar et al. 2007, Vaidya et al. 2010) that the efficacy of radiation of the tumor bed only in a selected group can be non-inferior to WBRT. The TARGIT E study should confirm the efficacy of a single dose of intraoperative radiotherapy (IORT) in a well selected group of elderly patients with small breast cancer and absence of risk factors. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines. Endpoints are the local relapse rate (within 2 cm of the tumor bed), ipsilateral relapse, cancer-specific and overall survival and contralateral breast cancer as well as documentation of quality of life and cosmetic outcome. The expected local relapse rates are 0.5/1/1.5% after 2.5/5/7.5 years, respectively. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 3/4/6% after 2.5/5/7.5 years. Power calculations result in 265 patients with a calculated loss to follow-up of 20%, an alpha of 0.05 and a beta 0.1. Only centers with access to the Intrabeam® system (Carl Zeiss) can recruit patients into the trial.

Official Title
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TARGIT-E(Elderly) Prospective Phase II Study of Intraoperative Radiotherapy (IORT) in Elderly Patients With Small Breast Cancer

Conditions
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Breast Neoplasms, Breast Diseases, Neoplasm Recurrence, Local, Neoplasms

Intervention / Treatment
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* Radiation: intraoperative radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: cT1c cN0 cM0 ≥ 70 years old invasive-ductal histology compliance informed consent Exclusion Criteria: extensive intraductal component (EIC) multifocality /-centricity lymph vessel invasion (L1) clinical signs of distant metastases or clinically suspicious lymph nodes other histology < 70 years old missing informed consent or non-compliance bilateral breast cancer at time of diagnosis known BRACA 1/2 mutations (genetic testing not required)

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraoperative radiotherapy<br>single arm with intraoperative radiotherapy | Radiation: intraoperative radiotherapy<br>* intraoperative single dose radiotherapy (20 Gy)<br>* Other names: IORT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Relapse | Rate of local relapse (within 2cm of the initial tumor bed) | up to ten years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Death is an event | up to ten years | 
| Ipsi- or Contralateral Breast Cancer | Rate of ipsilateral and contralateral breast cancer events | up to ten years | 
| Cosmesis | BCCT.Core analysis of cosmesis | up to 7.5 years | 
| General and breast-specific Quality of Life after IORT | EORTC questionnaires QLQ C30 and BR23 | up to 10 years | 
| Late toxicity after IORT | LENT-SOMA based toxicity at all FU time points | up to ten years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keywords provided by University Hospital Mannheim:, Intraoperative Radiotherapy, Early Breast Cancer, Elderly Patients