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
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
RATIONALE: It is not yet know whether higher per daily radiation therapy is equally as effective as standard per daily radiation therapy in treating breast cancer.
PURPOSE: This randomized phase III trial studies how well an accelerated course of higher per daily radiation therapy with concomitant boost works compared to standard per daily radiation therapy with a sequential boost in treating patients with early-stage breast cancer that was removed by surgery.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 vs. ≥ 50 years), prior chemotherapy (yes vs. no), estrogen-receptor status (+ vs. -), and histology grade (1-2 vs. 3). Patients are randomized to 1 of 2 treatment arms. Treatment begins within 9 weeks of last surgery or chemotherapy delivery.
After completion of study therapy, patients are followed at 1 month, at 6 months, and then yearly.
Inclusion criteria:
Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole breast irradiation with boost without regional nodal irradiation planned
The patient must be female
The patient must meet at least one of the three following criteria:
A. Pathological stage I, II Breast Cancer AND at least one of the following:
B. Pathological stage 0 breast cancer with nuclear grade 3 ductal carcinoma in situ (DCIS) and patient age <50 years or
C. Post-neoadjuvant pathological 0, I, II breast cancer resected by lumpectomy after neoadjuvant systemic therapy
Study entry must be within 50 days from whichever comes later: last surgery (breast or axilla) or last chemotherapy. The day of surgery is Day "0".
If multifocal breast cancer, then it must have been resected through a single lumpectomy incision with negative margins
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:
A focally positive resection margin
For invasive breast cancer the axilla must be staged by one of the following:
Sentinel node biopsy alone, if sentinel node is negative, i.e. any of the following:
Sentinel node biopsy alone, OR followed by axillary node dissection per investigator discretion, for clinically node negative patients as described below:
Axillary node dissection is required following sentinel node (SN) biopsy with a minimum total of 6 axillary nodes if any of the following exist:
Axillary dissection alone (with a minimum of 6 axillary nodes)
Age ≥ 18
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
Appropriate stage for protocol entry, including no clinical evidence for distant metastases, based upon the following minimum diagnostic workup:
Patients must have had ER analysis performed on the primary breast tumor prior to study entry according to current American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) Guideline Recommendations for hormone receptor testing. If negative for ER, assessment of PR must also be performed according to current ASCO/CAP Guideline Recommendations for hormone receptor testing (http://www.asco.org)
Complete blood count (CBC)/differential obtained within 14 days prior to study entry, with adequate bone marrow function defined as follows:
Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of study entry
Women of childbearing potential must be non-pregnant and non-lactating and willing to use medically acceptable form of contraception during radiation therapy
Patient must provide study specific informed consent prior to study entry
Breast implants allowed
Exclusion criteria:
American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, M1 pathologic stages III or IV breast cancer
Treatment plan that includes regional node irradiation
Prior invasive non-breast malignancy (except non-melanomatous skin cancer, carcinoma in situ of the cervix) unless disease free for a minimum of 5 years prior to study entry
Prior invasive or in-situ carcinoma of the breast [-prior lobular carcinoma in situ (LCIS) is eligible]
Two or more breast cancers not resectable through a single lumpectomy incision
Bilateral breast cancer
DCIS only (without an invasive component) and age ≥ 50 years
DCIS nuclear grade 1 or 2 only (without an invasive component) and age < 50 years
Invasive breast cancer and low risk for 5-year in breast recurrence after lumpectomy with negative margins that does not meet one of the eligibility factors in 3.1.3.
Unable to delineate on CT scan the extent of the target lumpectomy cavity for boost (Placement of surgical clips to assist in treatment planning of the boost is strongly recommended, see Section 6.4.2 for details)
Suspicious unresected microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign
Non-epithelial breast malignancies such as sarcoma or lymphoma
Paget's disease of the nipple
Male breast cancer
Prior radiotherapy to the breast or prior radiation to the region of the ipsilateral breast that would result in overlap of radiation therapy fields
Intention to administer concurrent chemotherapy for current breast cancer.
Severe, active co-morbidity, defined as follows:
Pregnancy or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception
Active systemic lupus, erythematosus, or any history of scleroderma, dermatomyositis with active rash
Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent
Cameron Park, California 95682, United States
Roseville, California 95661, United States
Sacramento, California 95817, United States
Vacaville, California 95687, United States
Deerfield Beach, Florida 33442, United States
Jacksonville, Florida 32207, United States
Jacksonville, Florida 32209, United States
Jacksonville Beach, Florida 32250, United States
Miami, Florida 33136, United States
Saint Augustine, Florida 32086, United States
Canandiaqua, New York 14424, United States
East Syracuse, New York 13057, United States
New York, New York 10032, United States
Morehead City, North Carolina 28557, United States
Wilmington, North Carolina 28401, United States
Hilton Head Island, South Carolina 29926, United States
Eau Claire, Wisconsin 54703, United States
Sturgeon Bay, Wisconsin 54235-1495, United States
Summit, Wisconsin 53066, United States
Saint John, New Brunswick E2L 4L2, Canada
Montreal, Quebec H3H 2R9, Canada