Breast Cancer
Conditions
Keywords
breast
Brief summary
This is a phase I- II feasibility study for delivering partial breast irradiation (PBI) in selected patients with early stage, lymph node negative, breast cancer after breast-conserving surgery using accelerated Intensity Modulated Radiotherapy (IMRT).
Detailed description
This is a non-randomized Phase I-II feasibility study of partial breast irradiation with accelerated IMRT technique. In this study, patients will be eligible if the estimated risk of breast cancer elsewhere in the breast (beyond the tumor bed) is low. The radiation treatment will be available to women who are older than 40 years, have a DCIS (Ductal carcinoma in situ) or T1, N0, M0, (AJCC classification, version 6.0), non-lobular infiltrating carcinoma treated with breast-conserving surgery. Patients will undergo a pre-treatment planning free breathing CT with 5mm cuts in the treatment position, on a breast board, with both arms extended above their head that will be used to plan the traditional two field (tangent) plan. An Active Breathing Control (ABC) device will be used to minimize target motion due to breathing during a second CT scan. The lumpectomy cavity will be identified and delineated, and margins of approximately 1.5 cm in three dimensions will be used to allow for subclinical tumor extension and daily set-up error. The organs at risk (heart, lungs, contralateral breast) will be contoured on both CT scans. An inverse planning system and optimization tools will be employed in order to achieve the best IMRT plan (to minimize the dose to the heart, lungs and contralateral breast), that will be compared to the two field plan. If the IMRT plan is shown to be the optimal one, in terms of doses to organs at risk, then the patient will be enrolled in the protocol and will proceed with the treatment. Treatment will start approximately two weeks after the planning CT is obtained. All patients on protocol will be treated with accelerated radiotherapy, 3.85 Gy per fraction, bid, for 5 consecutive days for a total dose of 38.5 Gy.
Interventions
RADIATIONIMRT
Patients on protocol will be treated with accelerated radiotherapy, 3.85 Gy per fraction, bid, for 5 consecutive days for a total dose of 38.5 Gy.
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with unifocal histologically proven breast cancer, with or without calcifications in mammogram. * DCIS (Ductal carcinoma in situ) (Tis, Stage 0) * Non-lobular infiltrating carcinoma, maximum of 2 cm in diameter. (T1, Stage I) * The patient was operated on and the tumor was excised with lumpectomy * The tumor is reported with negative margins \>3 mm, as per our hospital protocol. * For invasive carcinoma, axillary lymph nodes are negative by sentinel lymph node (SLN) mapping and biopsy or by formal axillary lymph node dissection. * The patient is over 40 years old with life expectancy of at least 5 years * Karnofsky status must be at least 70. See appendix I. * Pre- and post-menopausal women are eligible for entry. * The patient must be aware of the neoplastic nature of her disease and must be willing to consent after being informed of the potential benefits, side effects and risks of radiotherapy. Institutional Review Board approval of this protocol and a consent form is required.
Exclusion criteria
* No concurrent or neoadjuvant chemotherapy is allowed. Patient is permitted to be treated with chemotherapy or hormone therapy only after completion of the radiation treatment. * Patients with diffuse calcifications, multifocal or multicentric disease, lymph-vascular invasion are excluded. * Patients cannot participate if there is extensive LCIS (Lobular carcinoma in situ) in specimen or extensive DCIS. * Patients are excluded if systemic disease is present or the patient has been irradiated to the ipsilateral breast or the chest wall. * Patients who are carriers of BRCA 1/2 mutations or at high risk for hereditary breast cancer due to strong family history (more than one pre-menopausal family member with breast cancer or any ovarian cancer) are excluded because of the increased potential for in-breast recurrence elsewhere in the breast in the absence of whole breast radiotherapy. * Patients with scleroderma, or systemic or discoid lupus are excluded due to the potential for significant radiotherapy associated toxicity. * Pregnant woman cannot participate in the study. * Patients who have serious medical problems which would limit survival to \<5 years or a psychiatric condition which would prevent informed consent cannot participate. * Patients who are unable to lie on their back and raise their arms above their heads in the treatment planning position for radiotherapy are excluded. * Patients that have mammographically occult disease are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Local Control at 5 Years | 5 years | The primary objective was to determine the rate of local control (the arrest of cancer growth at the site of origin) of cancer in the treated breast at 5 years following breast-conserving surgery and partial breast radiotherapy using IMRT. |
| Percentage of Participants That Experience Cosmetic Adverse Events (AEs) | 5 years | The primary outcome was to determine the rate of acute cosmetic adverse events and late cosmetic adverse events at follow-up visits over 5 years. To determine the rate of adverse events, the percentage of participants experiencing no cosmetic AEs, at least 1 grade 1 toxicity, at least 1 grade 2 toxicity, and at least 1 grade 3 toxicity were calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dosimetric and Volumetric Differences Between Treatment Plans for Partial Breast Irradiation and Other Treatment Planning Methods | not specific | Dosimetric and volumetric differences between treatment plans for partial breast irradiation and other treatment planning methods for the target (partial breast) and organs at risk (e.g. heart, ipsilateral lung, contralateral breast)a subset of 20. |
| Mean Percentage of Reference Volume Receiving 19.25 Gy and 38.5Gy for Patients With Acceptable and Unacceptable Cosmesis | 5 years | One of the studies secondary outcomes was to evaluate the impact of short term accelerated partial breast radiation therapy on cosmetic results. To determine the association between dosimetric factors and cosmesis, the mean percentage of prescription dose received to WBV (Whole breast volume: corresponding region typically encompassed by traditional tangent fields) was compared among participants who developed fair/poor (F/P) cosmetic outcomes (unacceptable cosmesis) and participants who maintained excellent/good (E/G) cosmetic outcomes (acceptable cosmesis). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiotherapy Patients on protocol will be treated with accelerated radiotherapy, 3.85 Gy per fraction, bid, for 5 consecutive days for a total dose of 38.5 Gy. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Radiotherapy |
|---|---|
| Age, Continuous | 56 years |
| Chemotherapy No | 25 participants |
| Chemotherapy Yes | 5 participants |
| Endocrine Therapy No | 11 participants |
| Endocrine Therapy Yes | 19 participants |
| Histology DCIS | 16 participants |
| Histology IDC | 14 participants |
| Laterality Left Breast | 9 participants |
| Laterality Right Breast | 21 participants |
| Re-excision No | 15 participants |
| Re-excision Yes | 15 participants |
| Sex: Female, Male Female | 30 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 | 34 / 34 |
| serious Total, serious adverse events | 8 / 34 |
Outcome results
Primary
Percentage of Participants That Experience Cosmetic Adverse Events (AEs)
The primary outcome was to determine the rate of acute cosmetic adverse events and late cosmetic adverse events at follow-up visits over 5 years. To determine the rate of adverse events, the percentage of participants experiencing no cosmetic AEs, at least 1 grade 1 toxicity, at least 1 grade 2 toxicity, and at least 1 grade 3 toxicity were calculated.
Time frame: 5 years
Population: 34 for patients were enrolled and treated. 2 patients were excluded from all analysis due to fair baseline cosmesis. 2 additional patients underwent mastectomies and were therefore excluded from analysis (cosmesis could not be assessed at 5 years). 30 patients were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiotherapy | Percentage of Participants That Experience Cosmetic Adverse Events (AEs) | Experiences no toxicities | 23.3 percentage of participants |
| Radiotherapy | Percentage of Participants That Experience Cosmetic Adverse Events (AEs) | Experienced at least 1 grade 1 toxicity | 40 percentage of participants |
| Radiotherapy | Percentage of Participants That Experience Cosmetic Adverse Events (AEs) | Experienced at least 1 grade 2 toxicity | 30 percentage of participants |
| Radiotherapy | Percentage of Participants That Experience Cosmetic Adverse Events (AEs) | Experienced at least 1 grade 3 toxicity | 6.7 percentage of participants |
Primary
Rate of Local Control at 5 Years
The primary objective was to determine the rate of local control (the arrest of cancer growth at the site of origin) of cancer in the treated breast at 5 years following breast-conserving surgery and partial breast radiotherapy using IMRT.
Time frame: 5 years
Population: 34 for patients were enrolled and treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiotherapy | Rate of Local Control at 5 Years | 97 percentage of participants |
Secondary
Dosimetric and Volumetric Differences Between Treatment Plans for Partial Breast Irradiation and Other Treatment Planning Methods
Dosimetric and volumetric differences between treatment plans for partial breast irradiation and other treatment planning methods for the target (partial breast) and organs at risk (e.g. heart, ipsilateral lung, contralateral breast)a subset of 20.
Time frame: not specific
Population: At the time the study was written, we planned to compare treatment methods. Over the course of the study, it was determined additional analysis was not needed due to the analysis and publication of this outcome by several other investigators.
Secondary
Mean Percentage of Reference Volume Receiving 19.25 Gy and 38.5Gy for Patients With Acceptable and Unacceptable Cosmesis
One of the studies secondary outcomes was to evaluate the impact of short term accelerated partial breast radiation therapy on cosmetic results. To determine the association between dosimetric factors and cosmesis, the mean percentage of prescription dose received to WBV (Whole breast volume: corresponding region typically encompassed by traditional tangent fields) was compared among participants who developed fair/poor (F/P) cosmetic outcomes (unacceptable cosmesis) and participants who maintained excellent/good (E/G) cosmetic outcomes (acceptable cosmesis).
Time frame: 5 years
Population: 34 for patients were enrolled and treated. 2 patients were excluded from all analysis due to fair baseline cosmesis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Radiotherapy | Mean Percentage of Reference Volume Receiving 19.25 Gy and 38.5Gy for Patients With Acceptable and Unacceptable Cosmesis | Mean % receiving 19.25, Acceptable Cosmesis | 34.6 Percentage of reference volume |
| Radiotherapy | Mean Percentage of Reference Volume Receiving 19.25 Gy and 38.5Gy for Patients With Acceptable and Unacceptable Cosmesis | Mean % receiving 19.25, Unacceptable Cosmesis | 46.1 Percentage of reference volume |
| Radiotherapy | Mean Percentage of Reference Volume Receiving 19.25 Gy and 38.5Gy for Patients With Acceptable and Unacceptable Cosmesis | Mean % receiving 38.5, Acceptable Cosmesis | 15.5 Percentage of reference volume |
| Radiotherapy | Mean Percentage of Reference Volume Receiving 19.25 Gy and 38.5Gy for Patients With Acceptable and Unacceptable Cosmesis | Mean % receiving 38.5, Unacceptable Cosmesis | 23.0 Percentage of reference volume |