Trial to Compare Radiation Fibrosis With Five Versus Three Fractions

Partial breast irradiation (PBI) is becoming a new paradigm for breast cancer radiation. No
type I or II evidence is currently available to demonstrate equivalence to standard whole
breast radiotherapy, and a prospective randomized trial jointly sponsored by NSABP and
Radiation therapy Oncology Group (RTOG) (NSABP B-39 and RTOG 0413) has completed accruing
patients, comparing whole breast radiotherapy to PBI, either by brachytherapy or external
beam techniques (EB): results of this trial are pending. Until results of this or similar
trials are available, PBI remains a research domain, and it should be offered to patients
only in the context of a clinical experimental protocol. Despite the fact that less extensive
experience than that of brachytherapy is available, PBI delivery through an external-beam has
many advantages. First of all, it is likely to be more acceptable to the patient since it is
non-invasive and it does not require a surgical procedure or anesthesia. Moreover, since it
is delivered after surgery, the pathological analysis of the segmental mastectomy specimen is
available to inform the selection of the best candidates. In addition, EB-PBI is likely to
become more widely reproducible, since it does not rely on the experience and skills of the
radiation oncologist performing the brachytherapy implant. Besides, once the technique is
established, it can be widely applied at any facility provided with a linear accelerator,
without the risk presented by some brachytherapy approaches that cannot be completed because
of the unfavorable interplay of patient's anatomy with the technical limitations of the
applicator. Finally, in terms of health care economics, an external beam approach spares the
costs of an extra surgical procedure and several days as inpatient (in the case of Low dose
Rate (LDR) brachytherapy).

A prone approach for partial breast radiation has been tested at NYU in a clinical trial
sponsored by an IDEA grant of the Department of Defense (NYU 00-23). Results of the first 47
patient accrued originally demonstrated feasibility. Eligibility to this study was limited to
post-menopausal women with non-palpable, mammographically detected tumors. In addition, the
protocol required patients to have first refused to undergo standard six-week radiotherapy.
Five fractions of 6 Gy were delivered to the Planning Target Volume (PTV) over ten days
(Monday-Wednesday-Friday, Monday-Wednesday). The dose and fractionation was based on
radiobiological modeling, aimed at determining a dose to deliver in five fractions that would
achieve equivalence to the tumor control estimates of 50 Gy in 25 fractions, while
maintaining a risk of fibrosis at the tumor bed comparable to that of a standard regimen of
60 Gy in 30 fractions. An α/β = 4 for tumor control was used, and its validity has been
recently confirmed by the results of a prospective randomized trial comparing accelerated to
standard whole breast radiotherapy.

Inclusion Criteria:

1. Post-menopausal women with status post segmental mastectomy defined as either 1) at
least 2 years without menstrual period or 2) or patients older than 50 with
serological evidence of post-menopausal status or 3) hysterectomized patients of any
age with Follicle Stimulating Hormone (FSH) confirmation of post-menopausal status.

2. Stage 1 (pT1) breast cancer, excised with negative margins.

3. clinically N0 or No Regional Lymph node (pN0) or sentinel node negative

Exclusion Criteria:

1. Previous radiation therapy to the ipsilateral breast.

2. Presence of a proportion of Ductal Carcinoma in-situ (DCIS) in the core biopsy
specimen which is compatible with extensive intraductal component (EIC).