Phase II Multi-center Trial Evaluating 5 Fraction Stereotactic Partial Breast Irradiation Using Gammapod

The GammaPod is a new external beam radiotherapy device dedicated for stereotactic
radiotherapy of breast cancer (Xcision Medical Systems, LLC, Columbia, Maryland). The design
goal of the GammaPod has been the ability to deliver ablative doses with sharp gradients
under stereotactic image guidance. Highly focused radiation is achieved at the isocenter due
to the cross-firing from 36 radiation arcs generated by rotating 36 individual Cobalt-60
beams.In order to immobilize the breast during imaging and treatment and in order to get a
stereotactic localization of the breast target volume, a vacuum-assisted breast
immobilization cup with built-in stereotactic frame is used. The patient can be imaged on a
CT or MRI wearing the vacuum-assisted breast cup and then be transferred to the GammaPod for
treatment. Then, the planner is required to delineate the gross tumor volume (GTV) and its
subclinical extensions. Multiple targets within a breast are allowed.Different doses can be
prescribed to different targets.One benefit of using the GammaPod over the cyberknife for
breast SBRT, is elimination of the need for internal gold fiducial markers, which are
required for the cyberknife treatment.

Using a stereotactic technique for APBI allows smaller margins in comparison to a 3DCRT
technique. The total expansions on the RAPID trial (3DCRT APBI) were 1.0 cm CTV expansion on
the lumpectomy cavity and an additional 1.0 cm for PTV, for a total expansion of 2.0 cm. As a
3DCRT technique was used on the RAPID trial limited number of radiation beams were employed,
no Intensity Modulated Radiation Techniques allowed, and the margins used to create a PTV
were relatively large (total margin 2 cm).

As the GammaPod will allow us to minimize the volume of normal breast being irradiated, and
decrease the PTV volume we hypothesize that a stereotactic technique with the GammaPod will
allow us to improve on the 3 year global cosmesis rates (physician and patient) reported in
the RAPID trial (3DCRT) by 40% despite 5 daily fractions of SBRT (in contrast to 38.5Gy/10
fractions 3DCRT BID on the RAPID trial) The GammaPod was FDA approved 12-2017.

Inclusion Criteria:

Women who satisfy all of the following conditions will be eligible for this study.

1 DCIS or invasive ductal, medullary, papillary, mucinous (colloid), or tubular histologies
2. Age ≥ 18 years. 3. ECOG Performance status 0-2 4. Women of child-bearing potential must
agree to use adequate contraception (barrier method of birth control- condom or diaphragm
and spermicidal foam; intrauterine device, prescription birth control pills, or abstinence)
prior to study entry, for the duration of study participation, and for 90 days following
completion of therapy. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

5. A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the following
criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has
had menses at any time in the preceding 12 consecutive months).

6. Appropriate staging studies identifying as AJCC stage Tis, or T1-T2, N0 (N0i+). The
tumor size must be 3 cm or less.

7. Surgical treatment of the breast with lumpectomy with histologically confirmed
margins free of tumor (no ink on margin) for invasive disease, and at least 2mm for
Ductal Carcinoma In Situ.. (Re-excision of margins is permitted).

8. Gross disease within the breast must be unifocal. (Patients with microscopic
multifocality are eligible as long as the total extent of tumor, gross and
microscopic, occupies a volume with greatest dimension 3 cm or less).

9. Patients with invasive disease are required to have axillary staging including:
sentinel node biopsy or axillary dissection. Patients with DCIS are not required to
have axillary staging.

10. The target lumpectomy cavity must be clearly delineated or clips can be placed at
time of surgery to delineate cavity.

11. If adjuvant chemotherapy is planned after SPBI, it must begin no earlier than two
weeks following completion of radiation. Delivery of SPBI can be done prior to
adjuvant chemotherapy or after adjuvant chemotherapy. If SPBI radiation planned after
chemotherapy, a minimum of three weeks after chemotherapy, prior to start of radiation
is recommended.

12. Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

1. Men are not eligible for this study.

2. T2(>3.0 cm), T3, N1, stage III, or stage IV breast cancer

3. Positive non-axillary sentinel lymph nodes or evidence of suspicious supraclavicular,
infraclavicular, or internal mammary lymph nodes by imaging or physical exam, unless
biopsied and found to be negative for tumor.

4. Evidence by physical examination or mammography of other suspicious masses, densities,
or microcalcifications in either breast, unless biopsied and found to be benign.

5. Patients with non-epithelial breast malignancies such as sarcoma or lymphoma are
excluded.

6. Multicentric gross breast carcinoma (either DCIS or invasive cancer) or microscopic
breast carcinoma occupying a volume with maximum dimensions of more than 3
centimeters.

7. Paget's disease of the nipple.

8. Previous thoracic or breast radiation on ipsilateral side. Contralateral breast
radiation is not excluded.

9. Treatment plan that includes ipsilateral whole breast or ipsilateral regional nodal
irradiation.

10. Any prior treatment with radiation, endocrine therapy, or chemotherapy (in the
neoadjuvant setting) for currently diagnosed breast cancer prior to GammaPod
treatment- adjuvant chemotherapy is acceptable.

11. Patients with active collagen vascular disease, specifically dermatomyositis with a
CPK level above normal or active skin rash, systemic lupus erythematosis, or
scleroderma

12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, immunosuppressed patients or psychiatric illness/social situations that
would limit compliance with study requirements.

13. Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.

14. If the lumpectomy cavity is completely outside of the vacuum assisted breast cup, then
patient should not be treated on the GammaPod secondary to concerns of
reproducibility.

15. Transplant patients or any patients on immunosuppressive therapy