Breast Cancer
Conditions
Keywords
invasive ductal breast carcinoma, medullary ductal breast carcinoma with lymphocytic infiltrate, invasive lobular breast carcinoma, tubular ductal breast carcinoma, mucinous ductal breast carcinoma, ductal breast carcinoma in situ, lobular breast carcinoma in situ, recurrent breast cancer
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.
Interventions
RADIATION3D-Conformal External Beam
Radiation was to be delivered in 2 fractions per day, each of 1.5 Gy, separated by at least six hours, given in 15 consecutive working days to a total of 30 fractions and 45 Gy. Radiation was to be prescribed to the treatment unit isocenter, positioned at the approximate center of the planning target volume.
Sponsors
National Cancer Institute (NCI)
NRG Oncology
Radiation Therapy Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed locally recurrent breast carcinoma consistent with the following cell types: * Invasive ductal breast carcinoma * Medullary ductal breast carcinoma * Tubular ductal breast carcinoma * Mucinous ductal breast carcinoma * Lobular breast carcinoma * Ductal carcinoma in situ (DCIS) * No Paget disease of the nipple * Target lumpectomy cavity must be clearly defined and the target lumpectomy cavity/ whole-breast reference volume must be \< 30% based on a post-operative, pre-treatment CT scan * Tumor size ≤ 3 cm in greatest dimension on pathologic specimen * Negative histologic margins of resection and no tumor on ink following breast-preserving surgery of local recurrence (Re-excision is permitted to achieve negative margins) * Axilla negative or ≤ 3 positive lymph nodes without extracapsular extension * If the in-breast recurrence is DCIS and/or microinvasive disease, a sentinel lymph node (SLN) evaluation is not required, but if performed: * Patients with a negative sentinal lymph node (SLN) biopsy are eligible for enrollment * Patients with a positive SLN biopsy require an axillary lymph node (ALN) dissection (ALND is not required if the SLN is not identified) * Patient is eligible if 0-3 positive ALNs without extracapsular extension is documented * If the in-breast recurrence is invasive disease and: * No prior ALN dissection or SLN dissection only: * Patient is required to undergo axillary evaluation with either a SLN or ALN dissection * If the SLN is not identified or if the SLN is positive for metastatic disease then an ALN dissection is required * Patient is eligible for enrollment if encounter 0-3 positive lymph nodes without extracapsular extension * • Prior ALN dissection: negative clinical exam: patient is eligible for enrollment * It is recommended, but not required, that the patient undergo ultrasound evaluation of the axilla and the lymph node draining regions of the breast; any suspicious areas are to be biopsied and if positive followed with an ALN dissection * Patient is eligible for enrollment if biopsies are negative or 0-3 axillary lymph nodes without extracapsular extension are encountered * Prior ALN dissection: positive clinical exam: biopsy required * If biopsy is negative, patient is eligible for enrollment * If biopsy is positive an ALN dissection is required * Patient is eligible for enrollment if biopsies are negative or 0-3 axillary lymph nodes without extracapsular extension encountered * Ipsilateral breast mammogram and MRI within 120 days prior to study entry * Contralateral breast mammogram within 12 months of study entry * For invasive in-breast recurrence, no more than 120 days since whole-body (positron emission tomography) PET-CT scan OR CT scan of the chest, abdomen, and pelvis, and bone scan * No multicentric ipsilateral breast recurrence or regional recurrence (other than axilla) * Patients must have a breast technically amenable to partial-breast irradiation * No metastatic disease documented by physical exam or radiographic evaluation (for patients with invasive disease) * No skin involvement * No prior contralateral mastectomy * Estrogen and progesterone status must be known PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Menopausal status not specified * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other invasive malignancy within the past 3 years except ipsilateral breast cancer and/or nonmelanoma skin cancer * No collagenous diseases, specifically systemic lupus erythematosus, scleroderma, or dermatomyositis * No psychiatric or addictive disorders that would preclude obtaining informed consent PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 2 weeks since prior chemotherapy and recovered * No concurrent intensity-modulated radiotherapy * No concurrent chemotherapeutic agents, including trastuzumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 (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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Partial Breast Re-Irradiation Partial Breast Re-Irradiation (PBrI) 3D-Conformal External Beam 1.5 Gy x 15 (BID) to 45 Gy Total | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | No protocol treatment received | 3 |
| Overall Study | Protocol Violation | 4 |
Baseline characteristics
| Characteristic | Partial Breast Re-Irradiation |
|---|---|
| Age, Continuous | 67 years |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 58 |
| serious Total, serious adverse events | 3 / 58 |
Outcome results
Primary
Number of Participants With Grade 3+ Treatment-related Skin, Fibrosis, and Breast Pain Adverse Events
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.
Time frame: From the end of radiation to 1 year.
Population: The first 55 eligible patients who completed treatment and achieved 1 year of follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Partial Breast Re-Irradiation | Number of Participants With Grade 3+ Treatment-related Skin, Fibrosis, and Breast Pain Adverse Events | 1 participants |
Secondary
12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale
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.
Time frame: 12 Months from the start of radiation treatment.
Population: Eligible patients who consented to participate in the quality of life study and have baseline and 12-month BCTOS data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Partial Breast Re-Irradiation | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Excellent | 1.03 units on a scale | Standard Deviation 0.06 |
| Partial Breast Re-Irradiation | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Good | 1.14 units on a scale | Standard Deviation 0.25 |
| Partial Breast Re-Irradiation | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Fair | 1.55 units on a scale | Standard Deviation 0.53 |
| Partial Breast Re-Irradiation | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Poor | 1.06 units on a scale | Standard Deviation 0.09 |
| Cosmetic Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Poor | 2.48 units on a scale | Standard Deviation 1.21 |
| Cosmetic Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Excellent | 1.67 units on a scale | Standard Deviation 0.57 |
| Cosmetic Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Fair | 2.19 units on a scale | Standard Deviation 0.69 |
| Cosmetic Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Good | 1.88 units on a scale | Standard Deviation 0.44 |
| Breast-Specific Pain Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Poor | 2.50 units on a scale | Standard Deviation 1.18 |
| Breast-Specific Pain Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Good | 1.53 units on a scale | Standard Deviation 0.45 |
| Breast-Specific Pain Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Fair | 1.82 units on a scale | Standard Deviation 0.77 |
| Breast-Specific Pain Score | 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale | Physician 12-Month Score: Excellent | 1.33 units on a scale | Standard Deviation 0.47 |
p-value: 0.054Spearman rank-order correlation test
p-value: 0.044Spearman rank-order correlation test
p-value: 0.087Spearman rank-order correlation test
Secondary
Change in Patient-Reported Cosmetic Outcomes From Baseline to 12-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS)
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.
Time frame: Baseline and 12 months from the start of radiation treatment.
Population: Eligible patients who consented to participate in the quality of life study and have baseline and 12-month BCTOS data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Partial Breast Re-Irradiation | Change in Patient-Reported Cosmetic Outcomes From Baseline to 12-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) | Functional status | 0.04 units on a scale | Standard Deviation 0.41 |
| Partial Breast Re-Irradiation | Change in Patient-Reported Cosmetic Outcomes From Baseline to 12-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) | Cosmetic | 0.09 units on a scale | Standard Deviation 0.65 |
| Partial Breast Re-Irradiation | Change in Patient-Reported Cosmetic Outcomes From Baseline to 12-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) | Breast-specific pain | -0.21 units on a scale | Standard Deviation 0.62 |
Comparison: Functional status
Comparison: Cosmetic
Comparison: Breast-specific pain
Secondary
Change in Patient-Reported Cosmetic Outcomes From Baseline to 36-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS)
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.
Time frame: Baseline and 36 months from the start of radiation treatment.
Population: Eligible patients who consented to participate in the quality of life study and have baseline and 36-month BCTOS data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Partial Breast Re-Irradiation | Change in Patient-Reported Cosmetic Outcomes From Baseline to 36-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) | Functional status | -0.02 units on a scale | Standard Deviation 0.47 |
| Partial Breast Re-Irradiation | Change in Patient-Reported Cosmetic Outcomes From Baseline to 36-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) | Cosmetic | 0.19 units on a scale | Standard Deviation 0.59 |
| Partial Breast Re-Irradiation | Change in Patient-Reported Cosmetic Outcomes From Baseline to 36-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS) | Breast-specific pain | -0.20 units on a scale | Standard Deviation 0.72 |
Comparison: Functional status
Comparison: Cosmetic
Comparison: Breast-specific pain
Secondary
Distant Metastasis-free Survival
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.
Time frame: From registration to date of distant metastasis, death or last follow-up. Analysis occurs after all patient have been potentially followed for 3 years.
Population: All eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Partial Breast Re-Irradiation | Distant Metastasis-free Survival | 94.8 percentage of participants |
Secondary
Freedom From Mastectomy
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.
Time frame: From registration to date of mastectomy or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Population: All eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Partial Breast Re-Irradiation | Freedom From Mastectomy | 5.2 percentage of participants |
Secondary
In-breast Recurrence
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.
Time frame: From registration to date of recurrence or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Population: All eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Partial Breast Re-Irradiation | In-breast Recurrence | 3.7 percentage of participants |
Comparison: Assuming a 3-year rate of 25% using a chi-squared test, a sample size of 55 patients will ensure at least 90% probability of detecting a reduction in the 3-year ipsilateral in-breast recurrence rate from 25% to 9%, with a significance level of 0.05 (1-sided). In-breast recurrence will be estimated using the cumulative incidence method.p-value: 0.0002Chi-squared
Secondary
Mastectomy-free Survival
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.
Time frame: From registration to date of mastectomy, death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Population: All eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Partial Breast Re-Irradiation | Mastectomy-free Survival | 89.7 percentage of participants |
Secondary
Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs)
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.
Time frame: Prior to the start of radiation and 3 weeks after last radiation treatment.
Population: Eligible patients who consented to participate in the CTC portion of the trial
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Partial Breast Re-Irradiation | Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) | Pre-treatment | Detectable | 8 Participants |
| Partial Breast Re-Irradiation | Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) | Pre-treatment | Undetectable | 32 Participants |
| Partial Breast Re-Irradiation | Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) | Pre-treatment | Unevaluable | 7 Participants |
| Partial Breast Re-Irradiation | Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) | Post-treatment | Detectable | 8 Participants |
| Partial Breast Re-Irradiation | Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) | Post-treatment | Undetectable | 26 Participants |
| Partial Breast Re-Irradiation | Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) | Post-treatment | Unevaluable | 13 Participants |
Secondary
Number of Patients With Good/Excellent Cosmesis Using the NRG Oncology/Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale
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.
Time frame: Baseline,12, and 36 Months from the start of radiation treatment.
Population: Eligible patients who consented to participate in the quality of life study and have baseline data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Partial Breast Re-Irradiation | Number of Patients With Good/Excellent Cosmesis Using the NRG Oncology/Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale | 12-Month-Excellent/Good | 22 Participants |
| Partial Breast Re-Irradiation | Number of Patients With Good/Excellent Cosmesis Using the NRG Oncology/Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale | Baseline-Excellent/Good | 26 Participants |
| Partial Breast Re-Irradiation | Number of Patients With Good/Excellent Cosmesis Using the NRG Oncology/Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale | 36-Month-Excellent/Good | 14 Participants |
Secondary
Overall Survival
Failure is death due to any cause. Three-year overall survival rate was estimated using the Kaplan-Meier method.
Time frame: From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Population: All eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Partial Breast Re-Irradiation | Overall Survival | 94.8 percentage of participants |
Secondary
Treatment-related Adverse Events (AEs) Any Time
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.
Time frame: From the end of radiation to end of follow-up. Will be evaluated at the time of the primary analysis.
Population: All eligible patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Partial Breast Re-Irradiation | Treatment-related Adverse Events (AEs) Any Time | Grade 5 | 0 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events (AEs) Any Time | Grade 4 | 0 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events (AEs) Any Time | Grade 3 | 10.3 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events (AEs) Any Time | Grade 2 | 32.8 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events (AEs) Any Time | Grade 1 | 41.4 percentage of participants |
Secondary
Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation
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.
Time frame: After 1 year from the end of radiation.
Population: All eligible patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Partial Breast Re-Irradiation | Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation | Grade 5 | 0 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation | Grade 4 | 0 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation | Grade 3 | 6.9 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation | Grade 2 | 22.4 percentage of participants |
| Partial Breast Re-Irradiation | Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation | Grade 1 | 24.1 percentage of participants |