Clinical trial NCT00593346: Evaluation of Accelerated Partial Breast Brachytherapy
Official title: Evaluation of Accelerated Partial Breast Brachytherapy as the Sole Method of Radiation Therapy for Stage 0, 1 and II Lymph Node Negative Breast Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2008-01-15
Enrollment: 151
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Over the past two decades, breast conserving therapy (BCT) has become a major treatment modality for Stage I and II breast carcinoma. The major advantages of breast conserving therapy are superior cosmetic outcome and the reduced emotional and psychological trauma afforded by this procedure compared with conventional mastectomy. The principal disadvantage of BCT is its more complex and prolonged treatment regimen requiring approximately 6 weeks of external beam radiation therapy that poses problems for some patients such as the working woman, elderly patients, and those who live at a significant distance from a treatment center. These factors, along with the patient's geographic location, result in a smaller fraction of the patients who currently meet eligibility criteria for BCT actually receiving it, despite its cosmetic and probable psychological advantages. The logistical problems of BCT are primarily related to the protracted course of external beam radiation therapy to the whole breast. While some investigators reported what they believe to be acceptable local control rates in carefully selected patients treated by wide local excision without radiation therapy, the criteria for patient selection are controversial and poorly defined and probably restrict the access of many patients to breast conserving therapy.

If previous observations are valid and breast irradiation following tylectomy exerts its maximal effect in eradicating occult disease remaining in the immediate vicinity of the tylectomy site, can radiation therapy be directed only to the tissue surrounding the excision cavity of the breast, using brachytherapy alone? If so, the entire course of radiation therapy could be delivered over a 4 to 7 day period immediately following tylectomy and/or axillary dissection, thus markedly reducing treatment time. Brachytherapy also inherently provides a higher central dose to the volume most at risk for recurrence. Cosmetic outcome after the use of a brachytherapy boost after external whole breast radiotherapy is comparable or slightly inferior to electron beam boost radiation therapy

Detailed description: This study will evaluate the local control, cosmetic results, quality of life, and complication rates of brachytherapy when used as the sole method of radiation therapy for patients with stage 0,I, and II carcinoma of the breast treated with tylectomy, with histologically assessed negative surgical margins, N0 axillary nodes.

Eligibility criteria: Inclusion Criteria:

* AJCC stage 0, I, or II (TisN0, T1N0, T2N0 = 3 cm) histologically confirmed carcinoma of the breast, treated with tylectomy. Axillary sampling is required only for cases of invasive cancers. Tumor size is determined by the pathologist. Clinical size may be used if the pathologic size is indeterminate.
* Signed study-specific informed consent for participation in the study.
* Negative, or close but negative, inked histologic margins of tylectomy or reexcision specimen to be confirmed prior to placing the brachytherapy catheters. Margins generally are positive if there is invasive or noninvasive tumor at the inked resection margin, close but negative if the tumor is within 2 mm of the inked margin and negative if the tumor is at least 2 mm away from the inked edge.
* Negative post-tylectomy or post-reexcision mammography if cancer presented with malignancy-associated microcalcifications; no remaining suspicious microcalcifications in the breast before brachytherapy.
* For patients with invasive cancer, no positive axillary lymph nodes with at least 6 axillary lymph nodes sampled or a negative sentinel node.
* Invasive ductal, lobular, medullary, papillary, colloid (mucinous),or tubular histologies. Noninvasive ductal carcinoma in situ.
* Chemotherapy or hormonal therapy planned for = 2 weeks after removal of brachytherapy catheters is permitted. Hormonal therapy is allowed during brachytherapy at treating radiation oncologist's decision.
* Negative pregnancy test for premenopausal patients with an intact uterus

Exclusion Criteria:

* Patients with distant metastases.
* Patients with in-situ lobular carcinoma or nonepithelial breast malignancies such as sarcoma or lymphoma.
* Patients with proven multicentric carcinoma (tumors in different quadrants of the breast, or tumors separated by at least 4 cm) with other clinically or radiographically suspicious areas in the ipsilateral breast unless confirmed to be negative for malignancy by biopsy.
* Patients who are pregnant or lactating.
* Patients with histologically confirmed positive axillary nodes in the ipsilateral axilla. Palpable or radiographically suspicious contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
* Prior non-hormonal therapy for the present breast cancer, including radiation therapy or chemotherapy.
* Patients with systemic lupus erythematosis, scleroderma, or dermatomyositis with a CPK level above normal or with an active skin rash.
* Patients with coexisting medical conditions in whom life expectancy is \< 2 years.
* Patients with psychiatric or addictive disorders that would preclude obtaining informed consent or completing the full series of high dose rate brachytherapy treatments on an outpatient basis.
* Patients with Paget's disease of the nipple.
* Patients with skin involvement, regardless of tumor size.
* Patients with a breast unsatisfactory for brachytherapy. For example, if there is little breast tissue remaining between the skin and pectoralis muscle after surgery, placement of catheters is technically problematic.
* Patients with tylectomies so extensive that the cosmetic result is fair or poor prior to brachytherapy.
* Surgical margins which cannot be microscopically assessed or are positive at pathological evaluation.
* Any previously treated contralateral breast carcinoma or synchronous bilateral breast carcinoma.
* Other malignancy, except non-melanoma skin cancer, ≤ 5 years prior to participation in this study; the disease free interval from any prior carcinoma must be continuous.
* Time between final definitive breast procedure to radioactive source loading of the brachytherapy catheters is greater than 8 weeks.
* Patients with diffuse (\> 1 quadrant or \>5 cm in diameter) suspicious microcalcifications.
* Patients with suspicious microcalcifications remaining on the post-tylectomy mammogram

Primary outcomes:
measure: Local Control Using Ipsilateral Breast Tumor Recurrence Rates
timeFrame: 2 years after treatment completion
measure: Local Control as Measured by Ipsilateral Breast Tumor Recurrence Rates
timeFrame: 5 years after treatment completion
measure: Local Control Using Disease-free Survival Rates
timeFrame: 2 years after treatment completion
measure: Local Control Using Disease-free Survival Rates
timeFrame: 5 years after treatment completion
Secondary outcomes:
measure: Quality of Life Completion
timeFrame: 2 years
measure: Excellent-good Cosmetic Outcomes - Patient Reported
timeFrame: 3 years after completion of therapy
measure: Excellent-good Cosmetic Outcomes - Physician Reported
timeFrame: 3 years after completion of therapy
measure: Impressions of the Cause of Cosmesis Changes Over Time - Patient Reported
timeFrame: 3 years
measure: Cosmesis Outcome as Measured by Percentage of Breast Retraction Assessment (pBRA)
timeFrame: Pre-treatment and 3 years
measure: Presence or Absence of Complications
timeFrame: 5 years after treatment completion
measure: Occurrence of Mastectomy After Completion of Initial Breast-conserving Treatment
timeFrame: 5 years after treatment completion
measure: Frequency of Grade 3-4 Toxicities
timeFrame: Up to 1 year from completion of therapy
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Imran Zoberi, MD
role: PRINCIPAL_INVESTIGATOR
References: