|Phase III||Treatment||Active||18 and over||NCI, Other||RTOG 1005|
NCI-2011-02669, CDR0000700069, NCT01349322
RATIONALE: Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet know whether high-dose radiation therapy is more effective than standard radiation therapy in treating breast cancer.
PURPOSE: This randomized phase III trial studies how well high-dose radiation therapy works compared to standard radiation therapy in treating patients with early-stage breast cancer that was removed by surgery.
Further Study Information
- To determine whether an accelerated course of hypofractionated whole-breast irradiation (WBI) including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.
- To determine whether breast-related symptoms and cosmesis from accelerated WBI that is hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard WBI with sequential boost.
- To determine whether the risk of late cardiac toxicity in patients with left-sided breast cancer treated with hypofractionation will be non-inferior to conventional fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from CT-based treatment planning and NTCP calculations.
- To determine whether CT-based conformal methods intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a multi-institutional setting following lumpectomy in early-stage breast cancer patients and whether dose-volume analyses can be established to assess treatment adequacy and likelihood of toxicity.
- To determine that cosmetic results and breast-related symptoms 3 years after hypofractionated breast radiation with concomitant boost will not be inferior to that obtained 3 years after WBI with sequential boost.
- To determine whether future correlative studies can identify individual gene expressions and biological host factors associated with toxicity and/or local recurrence from standard and hypofractionated WBI.
- If shown to be non-inferior, to then determine if accelerated course of hypofractionated WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be superior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.
- To determine whether treatment costs for hypofractionated WBI with concomitant boost are not higher than WBI with sequential boost.
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.
- Arm I: Patients undergo standard whole-breast radiotherapy (WBI) comprising intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) 5 days a week for 3-5 weeks followed by a sequential radiotherapy boost to the lumpectomy area 5 days a week for 1-1½ weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients undergo accelerated hypofractionated WBI comprising IMRT or 3D-CRT with a concurrent boost to the lumpectomy area 5 days a week for 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients' tissue samples may be collected for future research studies.
After completion of study therapy, patients are followed up for 1 month, at 6 months, and then yearly.
- Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole-breast irradiation (WBI) with boost without regional nodal irradiation planned
- Must meet one of the following criteria:
- Stage I or II breast cancer AND at least one of the following:
- Age < 50 years
- Positive axillary nodes
- Lymphovascular space invasion (LVI)
- At least 2 close resection margins (> 0 mm to ≤ 2 mm)
- One close resection margin and extensive in-situ component (EIC)
- Focally positive resection margins
- Non-hormone-sensitive breast cancer (estrogen-receptor negative (ER-) and progesterone-receptor (PR-) negative)
- Grade III histology
- Oncotype recurrence score > 25
- Stage 0 breast cancer with nuclear grade 3 ductal carcinoma in situ (DCIS) and patient age < 50 years
- No DCIS and age > 50 years
- No DCIS and age < 50 years and nuclear grade 1 or 2
- Resected by lumpectomy after neoadjuvant systemic therapy
- 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:
- 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
- Two or more close resection margins
- A focally positive resection margin
- Allowable options for mandatory axillary staging include:
- Sentinel node biopsy alone (if sentinel node is negative, pN0, pN0[IHC-,+])
- Sentinel node biopsy alone, or followed by axillary node dissection, for clinically node-negative patients as described below:
- Microscopic sentinel node (SN) positive (pN1mic)
- One or two SNs positive (pN1) without extracapsular extension
- Negative SN biopsy after neoadjuvant chemotherapy
- SN biopsy followed by axillary dissection with a minimum total of 6 axillary nodes if any of the following exist:
- > 2 positive SN
- Solitary SN that is positive without other sentinel nodes dissected
- Clinically (by either imaging or examination) T3 disease
- Presence of one or more positive SNs with extracapsular extension, clinically node-positive disease, or LVI in the primary tumor
- Axillary dissection alone (with a minimum of 6 axillary nodes)
- CT-imaging of the ipsilateral breast within 28 days of study entry for the radiation treatment planning
- Must be able 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)
- 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
- Bilateral mammogram within 90 days prior to study entry
- Bilateral or right and left mammography within 90 days prior to neoadjuvant chemotherapy, diagnostic biopsy establishing diagnosis, or last surgery (breast or axilla)
- No prior invasive or in-situ carcinoma of the breast (prior LCIS is eligible)
- No American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, or M1 breast cancer
- Must not have two or more breast cancers that are not resectable through a single lumpectomy incision
- No invasive breast cancer and low-risk (see low risk features below) for 5-year in-breast recurrence after lumpectomy with negative margins, defined as:
- ≥ 70 years old, T1, N0, ER/PR+
- > 50 years old, T1, N0, grade 1-2 breast cancer, ER/PR+
- No suspicious unresected microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign
- No non-epithelial breast malignancies such as sarcoma or lymphoma
- No Paget disease of the nipple
- No male breast cancer
- Breast implants allowed
- ANC ≥ 1,800/mm³
- Platelet count ≥ 75,000/mm³
- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
- Negative serum pregnancy test within 14 days of study entry
- Women of childbearing potential must not be pregnant or nursing and willing to use medically acceptable form of contraception during radiotherapy
- No prior invasive non-breast malignancy (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless disease free for a minimum of 5 years prior to study entry
- No severely active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the past 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
- Acquired Immune-Deficiency Syndrome (AIDS) based upon current CDC definition
- HIV testing is not required for entry into this protocol
- No active systemic lupus, erythematosus, or any history of scleroderma or dermatomyositis with active rash
- Medical, psychiatric, or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Study entry must be within 50 days of last breast/axillary surgery and/or last chemotherapy
- No treatment plan that includes regional-node radiotherapy
- No prior radiotherapy to the breast or prior radiation to the region of the ipsilateral breast that would result in overlap of radiation therapy fields
- No intention to administer concurrent chemotherapy for current breast cancer
Trial Lead Organizations/Sponsors
Radiation Therapy Oncology GroupNational Cancer Institute
|Frank Vicini||Principal Investigator|
|Waukesha Memorial Hospital Regional Cancer Center|
|Wingate F. Clapper||Ph: 262-928-7632|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01349322
Information obtained from ClinicalTrials.gov on April 29, 2013
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