A Registry Study of Permanent Breast Seed Implant

Study Overview
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Brief Summary
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Women found to have early stage breast cancer will have their cancer surgically removed followed by radiation treatment to the entire breast, five times per week for several weeks. The radiation treatment prevents the cancer from growing back but creates skin burns. Several studies have showed that it is nor necessary treating the whole breast. The investigators team has pioneered a new therapy realizing the permanent implantation of tiny radioactive seeds into the surgical cavity in a single one hour procedure under light anesthesia. Patients live a normal life while receiving the radiation treatment. The results of a first clinical trial on 67 patients shows that the treatment is well tolerate and efficient. The purpose of the study is to offer the treatment in several places and to increase the cohort of patient to 420 to capture rare complications if any.

Detailed Description
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For early stage breast cancer, accelerated partial breast irradiation is an alternative treatment option to whole breast irradiation after breast conserving surgery. Our group has previously reported results of a Phase I/II study of permanent breast seed implant (PBSI) using palladium-103 seeds as an alternative to whole breast radiotherapy for well selected breast cancer patients. The procedure is realised in a single session under light sedation and local freezing. After a median FU of 54 months no patients has recurred on a cohort of 67 patients, and acute of delayed side effect compared favourably to external beam radiotherapy. Yet this study was a single centre study and the sample size did not allow evaluating appropriately the risk of serious adverse events (SAE). The current study propose evaluating SAE on a multicentre and larger cohort of 420 patients.

Official Title
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A Multicentre Registry Study of Permanent Breast Seed Implant (PBSI) for Early Stage Breast Cancers.

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Radiation: Permanent breast seeds implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A confirmed histological diagnosis of invasive breast carcinoma Treated by breast conserving surgery with axillary node dissection (with a minimum of 6 nodes sampled) or sentinel lymph node biopsy Surgical margins clear over or equal to 2 mm A maximum tumor size of 3 cm Age >= 50 years old ECOG performance status of 0 or 1 Informed consent signed Exclusion Criteria: Previous history of cancer other than curable skin SCC or Tis or T1 cervix Patient receiving anti-coagulant that cannot be stopped two weeks prior PBSI Autoimmune disorder Diabetes insulin-dependant Pregnancy Breast implants Psychiatric or addictive disorder that would preclude attending follow-up Post-operative breast infection Suspicious remaining microcalcification on post-surgery mammogram (unless biopsy proven benign) Lobular features on histology (pure or mixed) or sarcoma histology Node positive on axillary dissection or in the sentinel lymph node biopsy Extensive in situ carcinoma Multicentric disease (in more than one quadrant or separated by 2 cm or more) Paget's disease of the nipple Metastases Patients presenting a post-surgical fluid cavity ≥ 2.5 cm in diameter in any dimension as determined on the planning US Clear delineation of the target volume on CT is not possible Having a volume to be implanted over 120cc Having a target volume too close to skin such that the 85% isodose overlaps the skin surface) Having a target volume too close to the chest wall, such that there is a risk of perforating the chest wall

Ages Eligible for Study
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Minimum Age: 50 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: PBSI<br>PBSI is a form of accelerated partial breast irradiation involving the insertion of 103-palladium stranded seeds under ultra-sound guidance and light sedation after CT planning in lieu of whole breast adjuvant radiotherapy. | Radiation: Permanent breast seeds implant<br>* Patients are pre-planned using CT simulation. Implant is realised under light sedation and local freezing. Stranded seeds are inserted using a brachytherapy template that is immobilised to the planned target volume using a 'localization' needle. Patients is released the same day and Quality Assurance involves a 2 months post-implant CT<br>* Other names: Artemend;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events | Serious Adverse Events (SAE) is an unintended sign, symptom, or syndrome illness that occurs during the period of observation in the clinical study and that is life threatening or result in death. SAE will be coded using the NCI CTC V3.0 scale and corresponds to grade 4 or 5 signs or symptoms. | Initial and then yearly up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breast cancer local recurrence | Ipsilateral in-breast or chest wall recurrence is defined as evidence of invasive or in situ breast cancer (except LCIS) in the ipsilateral breast. Patients will have a biopsy of the suspicious lesion to confirm the diagnosis with documentation of the location. | Yearly up to 10 years | 
| Regional recurrence | Regional recurrence is defined as the development of tumor in regional nodes as well as the soft tissue of the ipsilateral axilla after axillary dissection. The regional recurrence is suspected on imaging and/or clinical symptoms and must be documented with fine needle aspiration. Also the localisation of the nodal recurrence must be reported (internal mammary chain, supra-clavicular area or axilla). | Yearly up to 10 years | 
| Metastases | Distant recurrence is defined as evidence of tumor in any area of the body. The metastasis recurrence should be proved by appropriate imaging, biopsy or fine needle aspiration | Yearly up to 10 years | 
| PBSI side effects | Any toxicity related to the radiation treatment, including skin and subcutaneous, or any other organ in case of seed migration will be coded using the NCI common toxicity criteria version 3.0 scale. | After procedure | 
| PBSI side effects | Any toxicity related to the radiation treatment, including skin and subcutaneous, or any other organ in case of seed migration will be coded using the NCI common toxicity criteria version 3.0 scale. | At 2 months | 
| PBSI side effect | Any toxicity related to the radiation treatment, including skin and subcutaneous, or any other organ in case of seed migration will be coded using the NCI common toxicity criteria version 3.0 scale. | At 6 months | 
| PBSI side effect | Any toxicity related to the radiation treatment, including skin and subcutaneous, or any other organ in case of seed migration will be coded using the NCI common toxicity criteria version 3.0 scale. Fat necrosis will be diagnosed either by mammography or clinically (prolonged indurations and pain in the area of seeds implantation without evidence of infection). | Yearly up to 10 years | 
| Cosmetic outcome | Cosmetic results will be evaluated at each follow-up visit by the treating radiation oncologist. An excellent cosmetic result score is assigned when the treated breast looked essentially the same as the contralateral breast (as it relates to radiation effects). A good cosmetic score is assigned for minimal but identifiable radiation effects of the treated breast. A fair score means significant radiation effects were readily observable. A poor score is used for severe sequelae of breast tissue secondary to radiation effects. | Yearly up to 10 years | 
| Survival | Patient survival, either free of cancer or with disease present will be recorded at follow-up appointments. | Yearly up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infiltrating ductal carcinoma, Brachytherapy