RTOG 1005: A Phase III Trial of Accelerated Whole Breast Irradiation with Hypofractionation plus Concurrent Boost Versus Standard Whole Breast Irradiation plus Sequential Boost for Early-Stage Breast Cancer

Summary

The current study proposes to establish a hypofractionation schedule (with a concurrent boost) that delivers a dose in only 3 weeks that can be applied to a broader patient population than enrolled in the existing hypofractionation studies (high-risk, large breasted, and those requiring chemotherapy) seen routinely in everyday practice. Patient inclusion criteria will be defined to include patients at higher than average risk for local recurrence who could most benefit from the addition of a tumor bed boost - age [Less Than] 50 years (even with DCiS), node positive breast cancer, lymphovascular space invasion, presence of an eiC with close ([Less Than] 2mm) resection margins, focally positive margins, and/or non-hormone sensitive breast cancer. if the proposed regimen were proven to provide equivalent low control even in these higher-risk patients, the impact on the treatment of the majority of breast cancer patients would be practice changing.

Participant Eligibility

3.1 Conditions for Patient Eligibility (10/21/13)
For questions concerning eligibility, please contact RTOG Data Management (via the RTOG
contact list on the RTOG website)
3.1.1 Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole
breast irradiation with boost without regional nodal irradiation planned
3.1.2 The patient must be female
3.1.3 The patient must meet at least one of the three following criteria:
A. pStage I, II Breast Cancer AND at least one of the following:

* Age < 50 years or

* Positive axillary nodes or

* Lymphovascular space invasion or

* 2 or more close resection margins (> 0 mm to <= 2 mm) or

* 1 close resection margin and extensive intraductal component (EIC) [Per
College of American Pathologist (CAP) Recommendation] or

* Focally positive resection margins or

* Non-hormone sensitive breast cancer (ER and PR-negative) or

* Grade III histology or

* Oncotype recurrence score > 25 or
B. pStage 0 breast cancer with nuclear grade 3 DCIS and patient age <50 years or
C. ypStage 0, I, II breast cancer resected by lumpectomy after neoadjuvant systemic
therapy
3.1.4 Study entry must be within 50 days from whichever comes later: last surgery (breast or
axilla) or last chemotherapy NOTE: The day of surgery is Day
* 0
*
3.1.5 If multifocal breast cancer, then it must have been resected through a single
lumpectomy incision with negative margins
3.1.6 Breast-conserving surgery with margins defined as follows: (also see 3.1.3 for
eligibility)

* Negative margins defined as no tumor at the resected specimen edge.

* Close resection margins > 0 mm to <= 2 mm. as follows:

* One close resection margin and EIC (per College of American
Pathologist (CAP) Recommendation)

* 2 or more close resection margins.

* A focally positive resection margin
3.1.7 For invasive breast cancer the axilla must be staged by one of the following:

* Sentinel node biopsy alone (if sentinel node is negative, pN0, pN0(IHC-,+));

* Sentinel node biopsy alone, OR followed by axillary node dissection per
investigator discretion, for clinically node negative patients as described below:
o microscopic sentinel node positive (pN1mic)
o one or two sentinel nodes positive (pN1) without extracapsular
extension
o negative sentinel node biopsy after neoadjuvant chemotherapy

* Axillary node dissection is required following sentinel node biopsy with a
minimum total of 6 axillary nodes if any of the following exist:
o for > 2 positive SN
o any positive SN biopsy after neoadjuvant chemotherapy
o for clinically (by either imaging or examination) T3 disease
o for extracapsular extension

* Axillary dissection alone (with a minimum of 6 axillary nodes)
3.1.8 Age >= 18
3.1.9 CT-imaging of the ipsilateral breast within 28 days prior to study entry for the radiation
treatment planning. Must be able to delineate on CT scan the extent of the target
lumpectomy cavity for boost
3.1.10 Appropriate stage for protocol entry, including no clinical evidence for distant
metastases, based upon the following minimum diagnostic workup:

* History/physical examination, including breast exam (inspection and palpation of
the breasts) and documentation of weight and Zubrod Performance Status of 0-
2 within 28 days prior to study entry;

* Right and left mammography within 90 days of diagnostic biopsy establishing
diagnosis
3.1.11 Patients must have had ER analysis performed on the primary breast tumor prior to
study entry according to current ASCO/CAP Guideline Recommendations for hormone
receptor testing. If negative for ER, assessment of PgR must also be performed
testing (http://www.asco.org)
3.1.12 CBC/differential obtained within 14 days prior to study entry, with adequate bone
marrow function defined as follows:

* Absolute neutrophil count (ANC) >= 1,800 cells/mm3

* Platelets >= 75,000 cells/mm3

* Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to
achieve Hgb >= 8.0 g/dl is acceptable.)
3.1.13 Women of childbearing potential must have a negative urine or serum pregnancy test
within 14 days of study entry
3.1.14 Women of childbearing potential must be non-pregnant and non-lactating and willing to
use medically acceptable form of contraception during radiation therapy
3.1.15 Patient must provide study specific informed consent prior to study entry
3.1.16 Breast implants allowed