Radiation Therapy in Treating Women With Locally Recurrent Breast Cancer Previously Treated With Repeat Breast-Preserving Surgery
- Conditions
- Breast Cancer
- Interventions
- Radiation: 3D-Conformal External Beam
- Registration Number
- NCT01082211
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery kill any remaining tumor cells and may be an effective treatment for breast cancer.
PURPOSE: This phase II trial is studying how well radiation therapy works in treating women with locally recurrent breast cancer previously treated with repeat breast-conserving surgery.
- Detailed Description
OBJECTIVES:
Primary
* To evaluate skin, breast, and chest wall adverse events occurring within 1 year after completion of 3D-conformal partial-breast re-irradiation following repeat breast-preserving surgery in patients with locally recurrent breast carcinoma.
Secondary
* To evaluate the adverse events occurring after 1 year from the completion of re-irradiation and at any time.
* To evaluate in-breast control rate in patients treated with this regimen.
* To evaluate freedom-from-mastectomy rate in these patients.
* To evaluate the rate of circulating tumor cells (CTCs) in this patient population and to document eradication of CTCs by locoregional therapy.
* To determine whether translational objective will correlate with eradication or presence of CTCs with in-breast recurrence and distant metastasis-free survival.
* To evaluate cosmesis as judged by the patient and independent evaluation.
* To evaluate distant metastasis-free survival, mastectomy-free survival, and overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients undergo 3-dimensional conformal accelerated partial-breast irradiation twice daily, 5 days a week, for 3 weeks.
Some patients undergo blood sample collection at baseline and within 3 weeks after completion of radiotherapy for circulating tumor cells analysis.
Some patients complete questionnaires on cosmesis at baseline and at 1 and 3 years following radiotherapy.
After completion of study therapy, patients are followed up periodically for 4-5 years and then every year thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 65
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Partial Breast Re-Irradiation 3D-Conformal External Beam Partial Breast Re-Irradiation (PBrI) 3D-Conformal External Beam 1.5 Gy x 15 (BID) to 45 Gy Total
- Primary Outcome Measures
Name Time Method Number of Participants With Grade 3+ Treatment-related Skin, Fibrosis, and Breast Pain Adverse Events From the end of radiation to 1 year. Adverse events (AEs) were graded with Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Based on a rate of 4% for the AEs of interest, a rate of ≥ 13% for these AEs with re-irradiation would be unacceptable. A sample size of 55 evaluable pts (eligible \& started protocol treatment) would provide: 86% power to conclude an unacceptable rate of the specified AEs, if the true AE rate was at least 13%; 93% probability to not conclude an unacceptable rate of the specified AEs, if the true AE rate is 4%. If ≥ 5 pts have treatment-related AEs, then the treatment-related AE rate was considered unacceptable.
- Secondary Outcome Measures
Name Time Method Overall Survival From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. Failure is death due to any cause. Three-year overall survival rate was estimated using the Kaplan-Meier method.
Mastectomy-free Survival From registration to date of mastectomy, death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. Failure is mastectomy of the treated breast or death due to any cause. Mastectomy-free survival rate at three years was estimated using the Kaplan-Meier method.
Change in Patient-Reported Cosmetic Outcomes From Baseline to 36-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) Baseline and 36 months from the start of radiation treatment. The Breast Cancer Treatment Outcome Scale (BCTOS) is a 22-item tool to assess cosmetic results using patient self-reports. This brief self-report instrument has high reliability and validity, and it has been used in a variety of previous studies on recovery from breast cancer treatment. It is comprised of three subscales (functional status, cosmetic status, and breast specific pain). Response options for each BCTOS item form a four-point Likert scale evaluating the differences between the treated and the untreated breast (1=no, 2=slight, 3=moderate, 4=large difference). The score for each subscale is the mean of the ratings over all items belonging to that specific subscale. Change was calculated as the value at 36 months minus the value at baseline. A positive change reflects a decline at 36 months and a negative change reflects an improvement at 36 months.
Treatment-related Adverse Events (AEs) Any Time From the end of radiation to end of follow-up. Will be evaluated at the time of the primary analysis. AEs were graded with Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. The overall highest grade for each patient was computed from all reported adverse events definitely, probably, or possibly related to protocol treatment.
Freedom From Mastectomy From registration to date of mastectomy or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. Failure is mastectomy of the treated breast. Mastectomy rate at 3 years is reported, using the cumulative incidence with death as competing risk. Mastectomy-free survival is reported in outcome measure 10.
Distant Metastasis-free Survival From registration to date of distant metastasis, death or last follow-up. Analysis occurs after all patient have been potentially followed for 3 years. Failures are appearance of ipsilateral axillary, infraclavicular, internal mammary, or supraclavicular recurrences; distant metastases confirmed radiographically and/or pathologically; or death due to any cause. Note that a distant metastases was only considered a treatment failure if accompanied by an in-breast recurrence.
In-breast Recurrence From registration to date of recurrence or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. The definition of treatment failure is histologic evidence of recurrent carcinoma, either invasive or non-invasive (except LCIS) in the ipsilateral breast. Clinical evidence of carcinoma by physical examination and/or mammograms and/or MRI will not be construed as evidence of treatment failure without biopsy proof but will be considered as suspicious for recurrence. Ipsilateral breast recurrences will be considered local (infield) if they occur within the prescription isodose volume; they will be considered peripheral if they occur between the prescription isodose volume and a volume 2 cm outside of the prescription isodose volume. Ipsilateral recurrences will be considered non-contiguous or extra field if they are beyond the peripheral volume described above.
Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) Prior to the start of radiation and 3 weeks after last radiation treatment. CTCs in peripheral blood were assessed using the CellSearch (trademark) system. A stringent algorithm was used to classify cell images as a CTC. A CTC must express EpCAM \[epithelial cell adhesion molecule\] and not leukocyte lineage-specific antigens, exhibit cytoplasmic expression of cytokeratin, and contain a nucleus that binds DAPI \[4',6-doamidino-2-phenylindole\]. A cell image is not a CTC if any of the previous criterion are missing. A subject is categorized as "Detectable" if the patient had a CTC and "Undetectable" if the subject had no CTCs. If neither category could be determined, then the subject was categorized as "Unevaluable."
Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation After 1 year from the end of radiation. AEs were graded with CTCAE version 4. The overall highest grade for each patient is computed from reported adverse events definitely, probably, or possibly related to protocol treatment occurring after one year from completion of re-irradiation.
Change in Patient-Reported Cosmetic Outcomes From Baseline to 12-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) Baseline and 12 months from the start of radiation treatment. The Breast Cancer Treatment Outcome Scale (BCTOS) is a 22-item tool to assess cosmetic results using patient self-reports. This brief self-report instrument has high reliability and validity, and it has been used in a variety of previous studies on recovery from breast cancer treatment. It is comprised of three subscales (functional status, cosmetic status, and breast specific pain). Response options for each BCTOS item form a four-point Likert scale evaluating the differences between the treated and the untreated breast (1=no, 2=slight, 3=moderate, 4=large difference). The score for each subscale is the mean of the ratings over all items belonging to that specific subscale. Change was calculated as the value at 12 months minus the value at baseline. A positive change reflects a decline at 12 months and a negative change reflects an improvement at 12 months.
12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale 12 Months from the start of radiation treatment. Patient-Reported BCTOS is comprised of 3 subscales (functional status, cosmetic status, breast specific pain). Responses for each item form a 4-point Likert scale evaluating the differences between the treated and untreated breast (1=no, 2=slight, 3=moderate, 4=large difference). Higher scores reflect poorer outcomes.
Physicians rated cosmesis using a 4 point NRG Oncology/RTOG established criteria scale:
Excellent - when compared to the untreated breast or the original appearance of the breast, there is minimal/no difference in the size or shape of the treated breast.
Good - there is a slight difference in the size or shape of the treated breast as compared to the opposite breast or the original appearance of the treated breast.
Fair - obvious differences in the size and shape of the treated breast. This change involves quarter or less of the breast.
Poor - marked change in the appearance of the treated breast involving more than a quarter of the breast tissue.Number of Patients With Good/Excellent Cosmesis Using the NRG Oncology/Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale Baseline,12, and 36 Months from the start of radiation treatment. Physicians rated cosmesis using a 4 point NRG Oncology/RTOG established criteria scale:
Excellent - when compared to the untreated breast or the original appearance of the breast, there is minimal/no difference in the size or shape of the treated breast.
Good - there is a slight difference in the size or shape of the treated breast as compared to the opposite breast or the original appearance of the treated breast.
Fair - obvious differences in the size and shape of the treated breast. This change involves quarter or less of the breast.
Poor - marked change in the appearance of the treated breast involving more than a quarter of the breast tissue.
Trial Locations
- Locations (58)
William Beaumont Hospital - Royal Oak Campus
🇺🇸Royal Oak, Michigan, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
Albert Einstein Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
St. Agnes Hospital Cancer Center
🇺🇸Baltimore, Maryland, United States
Central Maryland Oncology Center
🇺🇸Columbia, Maryland, United States
Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
🇺🇸Burbank, California, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
McLaren Cancer Institute
🇺🇸Flint, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
St. Barnabas Medical Center Cancer Center
🇺🇸Livingston, New Jersey, United States
Sands Cancer Center
🇺🇸Canandaigua, New York, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
🇺🇸Sleepy Hollow, New York, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Charles M. Barrett Cancer Center at University Hospital
🇺🇸Cincinnati, Ohio, United States
Arizona Center for Cancer Care - Peoria
🇺🇸Peoria, Arizona, United States
Tate Cancer Center at Baltimore Washington Medical Center
🇺🇸Glen Burnie, Maryland, United States
Greenebaum Cancer Center at University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Cancer Institute at St. John's Hospital
🇺🇸Springfield, Illinois, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Cape Cod Hospital
🇺🇸Hyannis, Massachusetts, United States
Seton Cancer Institute at Saint Mary's - Saginaw
🇺🇸Saginaw, Michigan, United States
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
🇺🇸Marlton, New Jersey, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish West County Hospital
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center - Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center - Rockville Centre
🇺🇸Rockville Centre, New York, United States
McDowell Cancer Center at Akron General Medical Center
🇺🇸Akron, Ohio, United States
Barberton Citizens Hospital
🇺🇸Barberton, Ohio, United States
Flower Hospital Cancer Center
🇺🇸Sylvania, Ohio, United States
Delaware County Regional Cancer Center at Delaware County Memorial Hospital
🇺🇸Drexel Hill, Pennsylvania, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Rosenfeld Cancer Center at Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
M. D. Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States
Community Memorial Hospital Cancer Care Center
🇺🇸Menomonee Falls, Wisconsin, United States
Columbia Saint Mary's Hospital - Ozaukee
🇺🇸Mequon, Wisconsin, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸Commack, New York, United States
JFK Medical Center
🇺🇸Atlantis, Florida, United States
University of Colorado Cancer Center at UC Health Sciences Center
🇺🇸Aurora, Colorado, United States
Saint Joseph Mercy Cancer Center
🇺🇸Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Highland Hospital of Rochester
🇺🇸Rochester, New York, United States
University Radiation Oncology at Parkridge Hospital
🇺🇸Rochester, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Columbia-Saint Mary's Cancer Care Center
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Cross Cancer Institute at University of Alberta
🇨🇦Edmonton, Alberta, Canada
Battle Creek Health System Cancer Care Center
🇺🇸Battle Creek, Michigan, United States
Butterworth Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Lacks Cancer Center at Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States