Breast Cancer
Conditions
Keywords
Breast, Cancer, Hypofractionated, Node-Positive Breast Cancer, Radiation Therapy, Comprehensive Radiation Therapy
Brief summary
The proposed study is being done to learn more about a particular dose of radiation treatment for breast cancer that is completed in a shorter amount of time than what has traditionally been used to treat breast cancer. Subjects are being asked to be in this research study because they have already had surgery for breast cancer and some cancer cells were found in their lymph nodes that drain the breast tissue.
Detailed description
Subjects who join the study will receive a shortened course of radiation treatment that will last approximately four (4) weeks, instead of the traditional six (6) week course that women have typically received in this situation. The shorter course subjects will receive is designed in a way that it is thought to be equivalent to the longer course. This shorter course has already been shown to be very safe and effective when treating breast cancer in the breast tissue only. However, because cancer cells were found in the lymph nodes that drain their breast, subjects require radiation to a larger area of their chest, armpit, and shoulder than has been completely tested with this experimental dose.
Interventions
COMBINATION_PRODUCTAdjuvant Hypofractionated Radiation
Hypofractionation is the delivery of radiotherapy in single daily doses greater than the 180-200 cGy. Hypofractionation, through use of larger doses per fraction and fewer total treatments, is a method of shortening overall treatment time in breast cancer therapy.
Sponsors
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
1. Adult women (≥18 years old) with breast cancer who have undergone surgery for their primary breast tumor (either lumpectomy or mastectomy +/- reconstruction) and are confirmed to have involved lymph nodes on surgical pathology. 2. Patient who have undergone either a total mastectomy or a lumpectomy are eligible. Acceptable procedures for assessment of axillary nodal status at the time of surgery include: * axillary node dissection; * sentinel node biopsy alone; or * sentinel node biopsy followed by axillary node dissection. 3. Eligible women include AJCC (American Joint Committee on Cancer) 7th ed. Stage cN0 or cN1 subsequently staged after surgery as Stage pIB (N1mic), pIIA, pIIB, pIIIA, pIIIB, or N3a (10 or more axillary nodes) only: note that ypN0 will also be eligible if pathologic confirmation of nodal involvement was documented prior to neoadjuvant chemotherapy and the patient was found to be node-negative at the time of surgery. Note that women less than 50 years of age, women who received chemotherapy, patients staged as pN0 (i+ or mol+), and large-breasted women are eligible for enrollment. 4. The patient must have recovered from surgery with the incision completely healed and no signs of infection. If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may interfere with delivery of radiation therapy should have resolved. The patient must have an ECOG performance status of 0 or 1 (KPS \>70%). 5. The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 180 days if chemotherapy is not delivered adjuvantly. If adjuvant chemotherapy was administered, the interval between the last chemotherapy treatment and randomization must be no more than 180 days. 6. Before the patient is enrolled, the consent form, including any addenda, must be signed and dated by the patient and the person who explains the study to that patient. 7. Subjects will have the ability to understand, and the willingness to sign a written informed consent document.
Exclusion criteria
1. patients \<18 years old 2. pregnant women 3. male patients 4. women with T4 disease, including inflammatory breast cancer 5. women who have declined or otherwise not received preceding surgery 6. women with positive margins after primary surgery 7. women with node-negative disease 8. women without histologic confirmation of nodal involvement 9. women more than 180 days out from primary breast surgery or adjuvant chemotherapy 10. patients with clinically detected or suspicious lymph node involvement not readily amenable to surgical treatment (≥cN2 disease) 11. patients with synchronous bilateral breast cancers 12. patients with prior ipsilateral thoracic or breast radiation 13. patients with distant metastatic disease (cM1) or a life expectancy of less than 5 years 14. active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma. 15. other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up. 16. patients with psychiatric or addictive disorders or other conditions that, in the opinion of the Investigator, would preclude the patient from meeting the study requirements. 17. patients with a separate non-cutaneous cancer diagnosis for which the patient has not been without evidence of disease for at least 5 years. Note: women \<50 years of age, women who received chemotherapy, pN0 (i+ or mol+), and large-breasted women are eligible for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-related Adverse Event of Interest | 12 months and 36 months | The composite endpoint is "yes" for a given patient if that patient experienced at least one of six component adverse events: lymphedema, shoulder ROM impairment, cardiac ischemia, symptomatic rib fracture, brachial plexopathy Grade 2 ('moderate symptoms; limiting instrumental activity of daily living (ADL)') or Grade 3 ('severe symptoms; limiting self-care ADL'), or Grade 2 pneumonitis (requires steroids). AEs were assessed by CTCAE version 4.03. |
| Number of Participants With Lymphedema Severity by Measuring Interlimb Circumference | 12 months and 36 months | An increase in interlimb arm circumference of at least 10% in the lower arm or the upper arm, or both, compared with the contralateral arm at the same timepoint, will be judged to be clinically significant lymphedema. Arm circumference 15 cm above the medial epicondyle (upper arms) and 15 cm below the medial epicondyle (lower arms) will be assessed at 12 months and at 36 months. |
| Number of Participants With Symptomatic Rib Fracture as Measured by Plain Film or CT | 12 months and 36 months | Symptomatic rib fracture will be diagnosed by evidence of a correlative lesion on plain film or CT. |
| Number of Participants With New Development of Ischemic Heart Disease as Measured by EKG | 12 months and 36 months | Ischemic heart disease will be measured by the new development of angina with corresponding EKG changes, or myocardial infraction. |
| Number of Participants Reporting Shoulder Stiffness as Measured by the EORTC QLQ-BR23 | 12 months and 36 months | Shoulder stiffness severity is assessed using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire breast cancer module (EORTC QLQ-BR23). It is assessed based on patient response to the questionnaire item, "During the past week, was it difficult to raise your arm or to move it sideways?", which is scored from 1 to 4 with 1 being "not at all" and 4 being "very much". Shoulder stiffness is identified in a patient when their response to that question is 3 or 4 AND if their response increased numerically from their response on day 1. |
| Number of Participants With Grade 2 or Higher Pneumonitis | 12 months and 36 months | Number of patients who experience pneumonitis as an adverse event at Grade 2 or higher as assessed by CTCAE v 4.03. |
| Number of Participants With Grade 2 or Higher Brachial Plexopathy | 12 months and 36 months | Number of patients who experience brachial plexopathy as an adverse event at Grade 2 or higher as assessed by CTCAE v 4.03. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Disease Recurrence | Up to 60 months | Recurrent disease presentation within axillary lymph node levels I, II, or III. The supraclavicular region is not included in this endpoint. |
| Number of Participants With Metastasis-free Survival | 12 months and 36 months | Measured by the time from date of enrollment to earlier of clinical detection of metastatic disease beyond the breast/chestwall and regional lymph nodes or death. |
| Number of Participants With Local-regional Failure Free Survival | 12 months and 36 months | Measured by the time from date of enrollment to earlier of clinical detection of any ipsilateral recurrent disease to the breast/chestwall or regional lymph nodes (levels I, II, III, supraclavicular, and internal mammary lymph nodes) or death. |
| Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-C30 | From baseline up to 12 months | Patient's quality of life from pre-treatment to post-treatment, reported by the quality of life questionnaire \[EORTC QLQ-C30 V1\]. Summary scores and missing data handling were performed according to the EORTC QLQ-C30. The minimum score is 0, and the maximum score is 100. A higher score is a better outcome. A change in score is defined as a score increase of at least 10 points at the 12 month mark compared to baseline. |
| Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-BR23 | Baseline to 1 year post-intervention | Patient's quality of life from pre-treatment to post-treatment, reported by the quality of life questionnaire breast cancer module \[EORTC QLQ-BR23 V1\]. Summary scores and missing data handling were performed according to the EORTC QLQ-BR23. The minimum score is 0, and the maximum score is 100. A higher score is a better outcome. A change in score is defined as a score increase of at least 10 points from baseline. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristine Fisher, MD, MPH
University of Colorado, Denver
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adjuvant Hypofractionated Radiation Adjuvant Hypofractionated Radiation (4005 cGy) will last 3-4 weeks with 15 treatments, +/- 4 additional fractions as a boost. Radiation should commence within 180 days of the date of primary surgery. Four additional fractions (a boost or conedown) to areas deemed to be at particularly high risk of recurrence may be added at the end of the radiation course. Fraction size for the boost treatment will continue at 267 cGy for an additional 1068 cGy in four fractions.
Adjuvant Hypofractionated Radiation: Hypofractionation is the delivery of radiotherapy in single daily doses greater than the 180-200 cGy. Hypofractionation, through use of larger doses per fraction and fewer total treatments, is a method of shortening overall treatment time in breast cancer therapy. | 108 |
| Total | 108 |
Baseline characteristics
| Characteristic | Adjuvant Hypofractionated Radiation |
|---|---|
| Age, Continuous | 53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 84 Participants |
| Region of Enrollment United States | 108 participants |
| Sex: Female, Male Female | 108 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 108 |
| other Total, other adverse events | 108 / 108 |
| serious Total, serious adverse events | 11 / 108 |
Outcome results
Primary
Number of Participants Reporting Shoulder Stiffness as Measured by the EORTC QLQ-BR23
Shoulder stiffness severity is assessed using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire breast cancer module (EORTC QLQ-BR23). It is assessed based on patient response to the questionnaire item, During the past week, was it difficult to raise your arm or to move it sideways?, which is scored from 1 to 4 with 1 being not at all and 4 being very much. Shoulder stiffness is identified in a patient when their response to that question is 3 or 4 AND if their response increased numerically from their response on day 1.
Time frame: 12 months and 36 months
Population: Patients were excluded if they were missing data for this event.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants Reporting Shoulder Stiffness as Measured by the EORTC QLQ-BR23 | 12 months | 5 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants Reporting Shoulder Stiffness as Measured by the EORTC QLQ-BR23 | 36 months | 6 Participants |
Primary
Number of Participants With at Least One Treatment-related Adverse Event of Interest
The composite endpoint is yes for a given patient if that patient experienced at least one of six component adverse events: lymphedema, shoulder ROM impairment, cardiac ischemia, symptomatic rib fracture, brachial plexopathy Grade 2 ('moderate symptoms; limiting instrumental activity of daily living (ADL)') or Grade 3 ('severe symptoms; limiting self-care ADL'), or Grade 2 pneumonitis (requires steroids). AEs were assessed by CTCAE version 4.03.
Time frame: 12 months and 36 months
Population: Patients are included in analysis for this outcome measure if they have an event recorded for at least one of the six components of the composite endpoint, or if they had non-missing data for all six components.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With at Least One Treatment-related Adverse Event of Interest | 12 months | 15 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With at Least One Treatment-related Adverse Event of Interest | 36 months | 20 Participants |
Primary
Number of Participants With Grade 2 or Higher Brachial Plexopathy
Number of patients who experience brachial plexopathy as an adverse event at Grade 2 or higher as assessed by CTCAE v 4.03.
Time frame: 12 months and 36 months
Population: Patients who were missing an assessment for this endpoint were excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With Grade 2 or Higher Brachial Plexopathy | 12 months | 0 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With Grade 2 or Higher Brachial Plexopathy | 36 months | 0 Participants |
Primary
Number of Participants With Grade 2 or Higher Pneumonitis
Number of patients who experience pneumonitis as an adverse event at Grade 2 or higher as assessed by CTCAE v 4.03.
Time frame: 12 months and 36 months
Population: Patients who were missing an assessment for this endpoint were excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With Grade 2 or Higher Pneumonitis | 12 months | 0 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With Grade 2 or Higher Pneumonitis | 36 months | 0 Participants |
Primary
Number of Participants With Lymphedema Severity by Measuring Interlimb Circumference
An increase in interlimb arm circumference of at least 10% in the lower arm or the upper arm, or both, compared with the contralateral arm at the same timepoint, will be judged to be clinically significant lymphedema. Arm circumference 15 cm above the medial epicondyle (upper arms) and 15 cm below the medial epicondyle (lower arms) will be assessed at 12 months and at 36 months.
Time frame: 12 months and 36 months
Population: Patients who were missing a follow-up assessment at the given dates were excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With Lymphedema Severity by Measuring Interlimb Circumference | 12 months | 11 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With Lymphedema Severity by Measuring Interlimb Circumference | 36 months | 15 Participants |
Primary
Number of Participants With New Development of Ischemic Heart Disease as Measured by EKG
Ischemic heart disease will be measured by the new development of angina with corresponding EKG changes, or myocardial infraction.
Time frame: 12 months and 36 months
Population: Patients who were missing a follow-up assessment for this outcome measure at the given time points were excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With New Development of Ischemic Heart Disease as Measured by EKG | 12 months | 0 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With New Development of Ischemic Heart Disease as Measured by EKG | 36 months | 0 Participants |
Primary
Number of Participants With Symptomatic Rib Fracture as Measured by Plain Film or CT
Symptomatic rib fracture will be diagnosed by evidence of a correlative lesion on plain film or CT.
Time frame: 12 months and 36 months
Population: Patients who were missing a follow-up assessment at the given times for this endpoint were excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With Symptomatic Rib Fracture as Measured by Plain Film or CT | 12 months | 0 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With Symptomatic Rib Fracture as Measured by Plain Film or CT | 36 months | 0 Participants |
Secondary
Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-BR23
Patient's quality of life from pre-treatment to post-treatment, reported by the quality of life questionnaire breast cancer module \[EORTC QLQ-BR23 V1\]. Summary scores and missing data handling were performed according to the EORTC QLQ-BR23. The minimum score is 0, and the maximum score is 100. A higher score is a better outcome. A change in score is defined as a score increase of at least 10 points from baseline.
Time frame: Baseline to 1 year post-intervention
Population: This is the number of patients who completed the EORTC QLQ-BR23 at both baseline and 1 year post-intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-BR23 | 17 Participants |
Secondary
Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-C30
Patient's quality of life from pre-treatment to post-treatment, reported by the quality of life questionnaire \[EORTC QLQ-C30 V1\]. Summary scores and missing data handling were performed according to the EORTC QLQ-C30. The minimum score is 0, and the maximum score is 100. A higher score is a better outcome. A change in score is defined as a score increase of at least 10 points at the 12 month mark compared to baseline.
Time frame: From baseline up to 12 months
Population: This is the number of patients who completed the EORTC QLQ-C30 at both baseline and 1 year post-intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-C30 | 21 Participants |
Secondary
Number of Participants With Disease Recurrence
Recurrent disease presentation within axillary lymph node levels I, II, or III. The supraclavicular region is not included in this endpoint.
Time frame: Up to 60 months
Population: 2 subjects of 108 total were excluded due to having no follow-up data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With Disease Recurrence | 0 Participants |
Secondary
Number of Participants With Local-regional Failure Free Survival
Measured by the time from date of enrollment to earlier of clinical detection of any ipsilateral recurrent disease to the breast/chestwall or regional lymph nodes (levels I, II, III, supraclavicular, and internal mammary lymph nodes) or death.
Time frame: 12 months and 36 months
Population: 2 participants did not have a follow-up visit where local or regional disease recurrence was assessed and were excluded from this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With Local-regional Failure Free Survival | 12 months | 106 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With Local-regional Failure Free Survival | 36 months | 104 Participants |
Secondary
Number of Participants With Metastasis-free Survival
Measured by the time from date of enrollment to earlier of clinical detection of metastatic disease beyond the breast/chestwall and regional lymph nodes or death.
Time frame: 12 months and 36 months
Population: 2 participants who did not have a follow-up visit to assess metastasis status were excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjuvant Hypofractionated Radiation | Number of Participants With Metastasis-free Survival | 12 months | 106 Participants |
| Adjuvant Hypofractionated Radiation | Number of Participants With Metastasis-free Survival | 36 months | 103 Participants |