Breast Cancer
Conditions
Keywords
Proton, Brachytherapy, Partial Breast Irradiation, 3D Conformal Photon
Brief summary
This is an open label phase II study to determine the safety and efficacy of a novel 3 fraction daily dosing regimen for accelerated partial breast irradiation (APBI) for early invasive and noninvasive breast cancer. The three techniques utilized are recognized as standard options for the delivery of APBI, and there is no evidence that either technique is superior or inferior to any other. The APBI technique utilized will be at the physician's discretion and will be based on technical considerations, availability at the treating radiation facility, insurance coverage, as well as patient preference.
Interventions
RADIATIONBrachytherapy APBI
RADIATION3D-CRT (photon) APBI
RADIATIONProton APBI
Sponsors
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female Age ≥ 50 years at diagnosis * Grade 1-3 invasive ductal, mucinous, tubular, colloidal, or pure ductal carcinoma in situ (DCIS) measuring ≤ 2cm (clinical stage T1). * Estrogen Receptor (ER)+ (ER- DCIS meeting other eligibility criteria are eligible) * Unicentric: Patients with microscopic multifocality are eligible as long as the total pathologic tumor size is \<2cm. * Surgical treatment of the breast must have been lumpectomy. * The final margins of the resected specimen must be histologically free of tumor. * Pathologically node negative Note: For patients with T1a, T1b, T1c invasive breast cancer (except T1mi), an axillary staging procedure should be performed (either sentinel lymph node biopsy alone or axillary dissection and the axillary node must be pathologically negative). Patients with N0 (i+) tumors on sentinel lymph node mapping or dissection (i.e., if the tumor deposit is 0.2mm or less as determined by immunohistochemistry or hematoxylin and eosin staining) will also be eligible. * ECOG Performance Status of 0 or 1 * Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only. * Ability to complete questionnaire(s) by themselves or with assistance. * Ability to elect radiotherapy care in conjunction with their physician * Able and willing to provide written informed consent * Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study). * Willing to provide tissue and blood samples for correlative research purposes * Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study, IRB number 15-000136
Exclusion criteria
* Any of the following because this study involves therapy that has known genotoxic, mutagenic and teratogenic effects: * Pregnant women * Nursing women * Women of childbearing potential who are unwilling to employ adequate contraception * Neoadjuvant chemotherapy * Prior history of ipsilateral breast cancer * Prior radiation therapy to the ipsilateral breast or thorax * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. * Active collagen-vascular disease that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. * Paget's disease of the breast * Proven multicentric carcinoma (DCIS or invasive) in more than one quadrant or separated by 4 or more centimeters or diffuse (\>1 quadrant) suspicious calcifications * Histologic evidence of angiolympatic invasion (ALI). Note: Cases termed focally suspicious for ALI but where no definitive ALI is found are eligible. * Surgical margins that cannot be microscopically assessed or that are positive * Pathologic tumor \>2cm in size * Metastatic disease * Patients for whom the delivery of APBI is not feasible or any of the dosimetric treatment criteria in section 9.7 have not been met. * BRCA 1/2 mutation Note: Patients are not required to undergo BRCA1 and BRCA2 or other genetic mutation tests in order to enroll on the study. However, in the event a patient is tested and is found to be a mutation carrier, she would be excluded from the study. * Breast implants (patients who have had implants removed are eligible). * Extensive intraductal component * Active connective tissue disease * Reduction mammoplasty if 3DCRT or proton APBI are planned * Last surgery \>10 weeks from enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Rate of Adverse Cosmesis (Defined as Fair or Poor Cosmesis) Compared to Baseline Using the Harvard Cosmetic Rating: | Baseline, 3 years | Participants end up being rated as fair or poor cosmesis from baseline. Excellent: treated breast nearly identical to untreated breast Good: treated breast slightly different than untreated (minimal but identifiable effects of the treated breast) Fair: Treated breast clearly different from untreated but not seriously distorted (significant radiation effects readily observable) Poor: Treated breast seriously distorted (severe sequelae of breast tissue secondary to radiation effects) |
Countries
United States
Participant flow
Recruitment details
170 Patients were registered, but 4 patients weren't assigned to a treatment.
Participants by arm
| Arm | Count |
|---|---|
| Catheter-based Brachytherapy APBI 7 Gy x 3 fractions\>
\> Brachytherapy APBI | 56 |
| 3D-CRT APBI 7.3 Gy x 3 fractions\>
\> 3D-CRT (photon) APBI | 58 |
| Proton APBI 7.3 Gy x 3 fractions\>
\> Proton APBI | 52 |
| Total | 166 |
Baseline characteristics
| Characteristic | Catheter-based Brachytherapy APBI | 3D-CRT APBI | Proton APBI | Total |
|---|---|---|---|---|
| Age, Continuous | 67.0 years | 66.2 years | 67.4 years | 66.8 years |
| ER Status Negative | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| ER Status Positive | 55 Participants | 56 Participants | 50 Participants | 161 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 52 Participants | 48 Participants | 150 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 4 Participants | 4 Participants | 14 Participants |
| Grade Grade I | 25 Participants | 17 Participants | 18 Participants | 60 Participants |
| Grade Grade II | 25 Participants | 30 Participants | 29 Participants | 84 Participants |
| Grade Grade III | 4 Participants | 7 Participants | 5 Participants | 16 Participants |
| Grade Unknown | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Histology DCIS | 11 Participants | 16 Participants | 10 Participants | 37 Participants |
| Histology IDC | 44 Participants | 36 Participants | 35 Participants | 115 Participants |
| Histology ILC | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Histology Invasive mammary carcinoma | 0 Participants | 5 Participants | 3 Participants | 8 Participants |
| Histology Mucinous | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Histology (grouped) DCIS | 11 Participants | 16 Participants | 10 Participants | 37 Participants |
| Histology (grouped) Invasive carcinoma | 45 Participants | 42 Participants | 42 Participants | 129 Participants |
| Ki67 value (%) | 9.2 percentage of cells | 10.6 percentage of cells | 13.1 percentage of cells | 10.0 percentage of cells |
| Laterality Left | 29 Participants | 32 Participants | 22 Participants | 83 Participants |
| Laterality Right | 27 Participants | 26 Participants | 30 Participants | 83 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) White | 54 Participants | 52 Participants | 50 Participants | 156 Participants |
| Sex: Female, Male Female | 56 Participants | 58 Participants | 52 Participants | 166 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| T-stage T0 | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| T-stage T1 | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| T-stage T1a | 8 Participants | 6 Participants | 6 Participants | 20 Participants |
| T-stage T1b | 26 Participants | 12 Participants | 6 Participants | 44 Participants |
| T-stage T1c | 10 Participants | 21 Participants | 27 Participants | 58 Participants |
| T-stage T2 | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| T-stage Tis | 10 Participants | 14 Participants | 10 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 58 | 1 / 52 |
| other Total, other adverse events | 44 / 56 | 42 / 57 | 39 / 50 |
| serious Total, serious adverse events | 0 / 56 | 0 / 57 | 1 / 50 |
Outcome results
Primary
Change in the Rate of Adverse Cosmesis (Defined as Fair or Poor Cosmesis) Compared to Baseline Using the Harvard Cosmetic Rating:
Participants end up being rated as fair or poor cosmesis from baseline. Excellent: treated breast nearly identical to untreated breast Good: treated breast slightly different than untreated (minimal but identifiable effects of the treated breast) Fair: Treated breast clearly different from untreated but not seriously distorted (significant radiation effects readily observable) Poor: Treated breast seriously distorted (severe sequelae of breast tissue secondary to radiation effects)
Time frame: Baseline, 3 years
Population: At 3 years, 131 patients were evaluated for adverse cosmesis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Catheter-based Brachytherapy APBI | Change in the Rate of Adverse Cosmesis (Defined as Fair or Poor Cosmesis) Compared to Baseline Using the Harvard Cosmetic Rating: | 2 Participants |
| 3D-CRT APBI | Change in the Rate of Adverse Cosmesis (Defined as Fair or Poor Cosmesis) Compared to Baseline Using the Harvard Cosmetic Rating: | 0 Participants |
| Proton APBI | Change in the Rate of Adverse Cosmesis (Defined as Fair or Poor Cosmesis) Compared to Baseline Using the Harvard Cosmetic Rating: | 0 Participants |