A Registry Study of Breast Microseed Treatment

For women diagnosed with early stage breast cancer, lumpectomy followed by radiation is a
common treatment option. Radiation treatment is typically delivered to the whole breast, five
times per week, for anywhere from 3 to 8 weeks. The radiation helps kill any cancer cells
that may have been left over following the surgery but causes skin burns. Many studies have
demonstrated that radiation to the whole breast is not necessary, that it can be delivered to
a portion of the breast where the cancer is more likely to recur.

A technique called a Permanent Breast Seed Implant (PBSI) involving the implantation of
radioactive seeds has been developed to deliver the radiation to a portion of the breast. The
procedure is performed on an out-patient basis under local anesthesia and light sedation.
Because the radioactive seeds are permanently implanted in the breast, the patient is able to
live a normal life while the seeds deliver the prescribed radiation to the breast.

Previous studies on Permanent Breast Seed Implant (PBSI) demonstrate that it is a safe and
effective alternative form of radiation for appropriately selected patients after lumpectomy.
However, those results have been obtained mainly from a single institution, with only 4
patients treated in another center. Further research is still needed to evaluate its safety
in a multi-center setting. The purpose of this study is to ensure the appropriate training of
clinicians who will be performing this procedure and to capture long term outcomes and rare
complications if any.

Due to the wide-spread use of mammography, breast cancer is commonly diagnosed at an early
stage. The standard treatment for early-stage disease is breast conserving surgery followed
by adjuvant radiation therapy to the whole breast. This approach leads to low recurrence
rates with a good cosmesis and provides an effective alternative to mastectomy. However, half
of these women will develop significant acute skin toxicity following whole breast
irradiation. These reactions occur more frequently in the infra-mammary fold, are associated
with pain, and are associated with a reduction in health-related quality of life. Whole
breast radiotherapy involves several daily treatments delivered over a period of 3 to 7 weeks
which can be disruptive for the patient's life.

To address these drawbacks, the concept of accelerated partial breast irradiation was
proposed. It arose out of the realization that the majority of tumor recurrences occur at or
near the region of the prior lumpectomy site, suggesting that for well selected patients only
the breast tissue surrounding the tumor bed might need radiation treatment. Accelerated
partial breast irradiation limits the radiation to a smaller portion of the breast
(surrounding the tumor cavity) and has the advantages of reducing radiation-induced toxicity
at increased convenience because it is delivered within a much shorter period of time. In
reducing the volume of breast treated, a higher dose of radiation can be delivered in each
treatment session. Accelerated partial breast irradiation advantages include a reduction of
the amount of irradiated skin and therefore the possibility to reduce radiation-induced skin
toxicity, and an increased convenience because it can be accelerated.

Several accelerated partial breast irradiation techniques have been reported including
external beam conformal irradiation, intra-operative radiotherapy and brachytherapy
techniques. Brachytherapy has been the most widely evaluated accelerated partial breast
irradiation technique. It involves the insertion of radioactive material directly into the
surgical cavity using tubes or catheters. Treatments are generally delivered as an outpatient
procedure using high dose rate (HDR) brachytherapy, delivering multiple treatments (8 to 10)
over a period of 5 to 8 days. Intra-operative radiotherapy is delivered in a single session
at the time of initial surgery.

A permanent breast seed implant (PBSI) technique of partial breast irradiation using
palladium (103Pd) seeds has been proposed. Similar to a permanent seed implant used to treat
prostate cancer, permanent breast seed implant (PBSI) involves the insertion of stranded
radioactive seeds under ultra-sound guidance. The advantages of the permanent breast seed
implant (PBSI) technique over other brachytherapy techniques include: i/- it is an
out-patient procedure performed in a single one-hour session under local anesthesia and light
sedation; ii/- it is performed after the surgery when the final pathology report is available
and the scar is completely healed; and iii/- the use of a low dose rate technique presents
the possible advantage to be more efficient and better tolerated compared to high dose rate
techniques.

The local recurrence rate, immediate and delayed toxicity, the radiation safety and quality
assurance data suggest that permanent breast seed implant (PBSI) is a safe and acceptable
option of accelerated partial breast irradiation, capable of delivering the right amount of
dose in the right location for selected early stage breast cancer. However, those results
have been obtained mainly from a single institution, with 4 patients treated in another
center. Further research is still needed to evaluate its safety in a multi-center setting and
also to detect serious adverse events when a larger number of patients are treated by a
larger group of practitioners. Since brachytherapy is operator dependent, a registry
represents a unique opportunity to ensure the appropriate training of radiation oncologist
and to capture capturing long terms outcomes.

Inclusion Criteria:

- Histological diagnosis of invasive or in-situ ductal carcinoma (DCIS)

- Treated by breast conserving surgery with axillary node dissection (with a minimum of
6 nodes sampled) or sentinel lymph node biopsy

- Surgical margins clear for invasive carcinoma (no tumor at ink margin) or superior or
equal to 2 mm for in-situ ductal carcinoma (DCIS)

- A maximum tumor size of 3 cm

- Age ≥50 years old

- Informed consent signed if participating in the Registry

Exclusion Criteria:

- No previous cancer unless in remission for more than 2 years.

- Active auto immune disorder with severe vasculitis component

- Uncontrolled and complicated insulin-dependent diabetes

- Pregnancy

- Cosmetic breast implants

- Psychiatric or addictive disorder that would preclude attending follow-up

- Post-operative breast infection requiring prolonged antibiotic therapy

- Lobular features on histology (pure or mixed) or sarcoma histology

- Node macroscopically 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 with a large post-surgical fluid cavity as determined on the
planning Ultrasound (US), resistant to the application of hot compresses for 4 weeks

- Clear delineation of the target volume on Computerized Tomography (CT) is not possible

- Volume to be implanted over 150cc

- Target volume too close to skin such that the 90% isodose overlaps the skin surface