Breast Cancer
Conditions
Keywords
Magnetic Resonance Imaging, Functional, Tomography, Positron-Emission, chemotherapy
Brief summary
The purpose of this study is: To validate the efficacy of multiparametric MRI, FDG-PET, RGD-PET, and PET-MR fusion imaging in the prediction and monitoring response to neoadjuvant chemotherapy of locally advanced breast cancer patients. To identify the optimal combination parameters of MR spectroscopy, diffusion-weighted MRI, dynamic contrast-enhanced MRI, FDG-PET, and RGD-PET in the prediction and monitoring response to neoadjuvant chemotherapy of locally advanced breast cancer patients. To compare the performances of dynamic contrast-enhanced MRI using parametric response map analysis versus those of pharmacokinetic parameters (Ktrans, kep, or Ve) in the early prediction of pathological responsiveness to neoadjuvant chemotherapy in breast cancer patients
Detailed description
Enrolled women with breast cancers who had received an anthracycline-taxane regimen and subsequent surgery were prospectively enrolled. DCE-MRI and FDG-PET scan were performed before and after the 1st cycle of chemotherapy. MR imaging parameters and SUV on PET scan within a tumor were analyzed. Clinicopathologic (age, clinical tumor stage, hormonal receptor status, and surgery type) and imaging parameters were compared according to the pathological response.
Interventions
None listed
Sponsors
Ministry of Health & Welfare, Korea
Seoul National University Hospital
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed breast cancer * Clinical stage IIb, IIIa, IIIb, IIIc * Must have measurable disease * Performance status of ECOG 0-2 * Adequate, bone marrow, liver, heart, and renal function * Who did not receive chemotherapy for breast cancer * Must agree with and signed informed consent
Exclusion criteria
* Prior history of cancer besides breast cancer * Active bacterial infection * Pregnant or lactating women * Psychological disease or seizure * History of arrhythmia, congestive heart failure, myocardial infarct, or unstable angina * Male breast cancer * Who had a pacemaker or history of open heart surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patholocial Response to Chemotherapy | Post-operation | Pathological complete response (pCR) or non-pCR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extracellular Extravascular Space Per Unit Volume of Tissue (Ve) | Baseline, post-1st chemotherapy | — |
| Tumor Size | baseline, completion of 1st cycle of chemotherapy | Maximal tumor diameter measured on magnetic resonance imaging |
| Tumor Volume | Baseline, post-1st chemotherapy | Tumor volume measured on 3-dimensional magnetic resonance imaging |
| Rate Constant of the Escape of the Contrast Agent From the Extracellular Extravascular Space Into the Plasma Compartment (Kep) | Baseline, post-1st chemotherapy | — |
| Constant for the Transfer of the Contrast Agent From the Plasma Compartment Into the Extracellular Extravascular Space (Ktrans) | Baseline, post-1st chemotherapy | — |
| Total Choline Amount of the Tumor Measured on Single Voxel 1H-magnetic Resonance Spectroscopy | Baseline, post-1st chemotherapy | Single voxel 1H-magnetic resonance spectroscopy quantifies the amount of total choline-containing compounds of a tumor, which indicates cellular proliferation and malignant transformation. |
| Standardized Uptake Value on 18F-fluoro-deoxy-glucose Positron Emission Tomography | Baseline, post-1st chemotherapy | — |
| Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI) | Baseline, post-1st chemotherapy | Parametric response map analysis using a software calculates the interval change of signal intensity based on a voxel-to-voxel comparison between measurements at baseline and after the first cycle of chemotherapy. PRMSI+ indicates proportions of voxels within a tumor with increased signal intensity. PRMSI- indicates proportions of voxels within a tumor with decreased signal intensity. PRMSI0 indicates proportions of voxels within a tumor with unchanged signal intensity. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pathologic Complete Responders (pCR) The absence of invasive tumor cells (ductal carcinoma in situ may have been present) after surgery. | 6 |
| Non-pCR The presence of invasive tumor cells (ductal carcinoma in situ may have been present) after surgery. | 42 |
| Total | 48 |
Baseline characteristics
| Characteristic | Pathologic Complete Responders (pCR) | Non-pCR | Total |
|---|---|---|---|
| Age, Customized 40 years old or less | 2 participants | 9 participants | 11 participants |
| Age, Customized more than 40 years old | 4 participants | 33 participants | 37 participants |
| Clinical stage (American Joint Committee on Cancer 7th edition) Stage II | 2 participants | 8 participants | 10 participants |
| Clinical stage (American Joint Committee on Cancer 7th edition) Stage III | 4 participants | 34 participants | 38 participants |
| Estrogen receptor Negative | 5 participants | 16 participants | 21 participants |
| Estrogen receptor Positive | 1 participants | 26 participants | 27 participants |
| HER2 Negative | 5 participants | 32 participants | 37 participants |
| HER2 Positive | 1 participants | 10 participants | 11 participants |
| Immunohistochemical subtype HER2-positive | 1 participants | 6 participants | 7 participants |
| Immunohistochemical subtype Hormone receptor positive | 1 participants | 26 participants | 27 participants |
| Immunohistochemical subtype Triple negative | 4 participants | 10 participants | 14 participants |
| Ki-67 (Cellular marker for proliferation) 14% or less (low proliferation) | 2 participants | 28 participants | 30 participants |
| Ki-67 (Cellular marker for proliferation) more than 14% (high proliferation) | 4 participants | 14 participants | 18 participants |
| Progesterone receptor Negative | 5 participants | 31 participants | 36 participants |
| Progesterone receptor Positive | 1 participants | 11 participants | 12 participants |
| Sex: Female, Male Female | 6 Participants | 42 Participants | 48 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 42 |
| serious Total, serious adverse events | 0 / 6 | 0 / 42 |
Outcome results
Primary
Patholocial Response to Chemotherapy
Pathological complete response (pCR) or non-pCR
Time frame: Post-operation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pathologic Response to Chemotherapy | Patholocial Response to Chemotherapy | Pathologic completer Responders (pCR) | 6 participants |
| Pathologic Response to Chemotherapy | Patholocial Response to Chemotherapy | Non-pCR | 42 participants |
Secondary
Constant for the Transfer of the Contrast Agent From the Plasma Compartment Into the Extracellular Extravascular Space (Ktrans)
Time frame: Baseline, post-1st chemotherapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Constant for the Transfer of the Contrast Agent From the Plasma Compartment Into the Extracellular Extravascular Space (Ktrans) | Baseline Ktrans | 0.263 min-1 | Standard Deviation 0.044 |
| Pathologic Response to Chemotherapy | Constant for the Transfer of the Contrast Agent From the Plasma Compartment Into the Extracellular Extravascular Space (Ktrans) | Post-1st chemotherapy Ktrans | 0.224 min-1 | Standard Deviation 0.076 |
| Non-pCR | Constant for the Transfer of the Contrast Agent From the Plasma Compartment Into the Extracellular Extravascular Space (Ktrans) | Baseline Ktrans | 0.254 min-1 | Standard Deviation 0.08 |
| Non-pCR | Constant for the Transfer of the Contrast Agent From the Plasma Compartment Into the Extracellular Extravascular Space (Ktrans) | Post-1st chemotherapy Ktrans | 0.234 min-1 | Standard Deviation 0.068 |
Secondary
Extracellular Extravascular Space Per Unit Volume of Tissue (Ve)
Time frame: Baseline, post-1st chemotherapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Extracellular Extravascular Space Per Unit Volume of Tissue (Ve) | Post-1st chemotherapy | 0.467 unitless | Standard Deviation 0.151 |
| Pathologic Response to Chemotherapy | Extracellular Extravascular Space Per Unit Volume of Tissue (Ve) | Baseline | 0.563 unitless | Standard Deviation 0.129 |
| Non-pCR | Extracellular Extravascular Space Per Unit Volume of Tissue (Ve) | Post-1st chemotherapy | 0.557 unitless | Standard Deviation 0.136 |
| Non-pCR | Extracellular Extravascular Space Per Unit Volume of Tissue (Ve) | Baseline | 0.550 unitless | Standard Deviation 0.146 |
Secondary
Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI)
Parametric response map analysis using a software calculates the interval change of signal intensity based on a voxel-to-voxel comparison between measurements at baseline and after the first cycle of chemotherapy. PRMSI+ indicates proportions of voxels within a tumor with increased signal intensity. PRMSI- indicates proportions of voxels within a tumor with decreased signal intensity. PRMSI0 indicates proportions of voxels within a tumor with unchanged signal intensity.
Time frame: Baseline, post-1st chemotherapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI) | PRMSI+ | 14.0 % of voxels | Standard Deviation 6.5 |
| Pathologic Response to Chemotherapy | Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI) | PRMSI- | 83.4 % of voxels | Standard Deviation 7.6 |
| Pathologic Response to Chemotherapy | Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI) | PRMSI0 | 2.7 % of voxels | Standard Deviation 1.4 |
| Non-pCR | Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI) | PRMSI- | 56.4 % of voxels | Standard Deviation 27.8 |
| Non-pCR | Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI) | PRMSI0 | 2.9 % of voxels | Standard Deviation 1.5 |
| Non-pCR | Proportions of Voxels Within a Tumor With Increased or Decreased Signal Intensity (Parametric Response Map Signal Intensity; PRMSI) | PRMSI+ | 40.7 % of voxels | Standard Deviation 27.2 |
Secondary
Rate Constant of the Escape of the Contrast Agent From the Extracellular Extravascular Space Into the Plasma Compartment (Kep)
Time frame: Baseline, post-1st chemotherapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Rate Constant of the Escape of the Contrast Agent From the Extracellular Extravascular Space Into the Plasma Compartment (Kep) | Baseline | 0.616 min-1 | Standard Deviation 0.262 |
| Pathologic Response to Chemotherapy | Rate Constant of the Escape of the Contrast Agent From the Extracellular Extravascular Space Into the Plasma Compartment (Kep) | Post-1st chemotherapy | 0.992 min-1 | Standard Deviation 0.917 |
| Non-pCR | Rate Constant of the Escape of the Contrast Agent From the Extracellular Extravascular Space Into the Plasma Compartment (Kep) | Baseline | 0.787 min-1 | Standard Deviation 0.729 |
| Non-pCR | Rate Constant of the Escape of the Contrast Agent From the Extracellular Extravascular Space Into the Plasma Compartment (Kep) | Post-1st chemotherapy | 0.616 min-1 | Standard Deviation 0.298 |
Secondary
Standardized Uptake Value on 18F-fluoro-deoxy-glucose Positron Emission Tomography
Time frame: Baseline, post-1st chemotherapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Standardized Uptake Value on 18F-fluoro-deoxy-glucose Positron Emission Tomography | Baseline | 18.9 unitless | Standard Deviation 12.1 |
| Pathologic Response to Chemotherapy | Standardized Uptake Value on 18F-fluoro-deoxy-glucose Positron Emission Tomography | Post-1st chemotherapy | 9.7 unitless | Standard Deviation 10.7 |
| Non-pCR | Standardized Uptake Value on 18F-fluoro-deoxy-glucose Positron Emission Tomography | Baseline | 10.7 unitless | Standard Deviation 5.6 |
| Non-pCR | Standardized Uptake Value on 18F-fluoro-deoxy-glucose Positron Emission Tomography | Post-1st chemotherapy | 7.6 unitless | Standard Deviation 4.4 |
Secondary
Total Choline Amount of the Tumor Measured on Single Voxel 1H-magnetic Resonance Spectroscopy
Single voxel 1H-magnetic resonance spectroscopy quantifies the amount of total choline-containing compounds of a tumor, which indicates cellular proliferation and malignant transformation.
Time frame: Baseline, post-1st chemotherapy
Population: Of the 48 participants, 13 participants did not undergo magnetic resonance spectroscopy examinations due to workflow problem. We included the available data from 35 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Total Choline Amount of the Tumor Measured on Single Voxel 1H-magnetic Resonance Spectroscopy | Baseline | 15.0 unitless | Standard Deviation 8.4 |
| Pathologic Response to Chemotherapy | Total Choline Amount of the Tumor Measured on Single Voxel 1H-magnetic Resonance Spectroscopy | Post-1st chemotherapy | 3.4 unitless | Standard Deviation 2.8 |
| Non-pCR | Total Choline Amount of the Tumor Measured on Single Voxel 1H-magnetic Resonance Spectroscopy | Baseline | 13.5 unitless | Standard Deviation 11.5 |
| Non-pCR | Total Choline Amount of the Tumor Measured on Single Voxel 1H-magnetic Resonance Spectroscopy | Post-1st chemotherapy | 7.8 unitless | Standard Deviation 6.3 |
Secondary
Tumor Size
Maximal tumor diameter measured on magnetic resonance imaging
Time frame: baseline, completion of 1st cycle of chemotherapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Tumor Size | Post-1st chemotherapy tumor size | 4.2 cm | Standard Deviation 1.8 |
| Pathologic Response to Chemotherapy | Tumor Size | Baseline tumor size | 4.9 cm | Standard Deviation 1.8 |
| Non-pCR | Tumor Size | Baseline tumor size | 5.0 cm | Standard Deviation 2 |
| Non-pCR | Tumor Size | Post-1st chemotherapy tumor size | 4.5 cm | Standard Deviation 1.8 |
Secondary
Tumor Volume
Tumor volume measured on 3-dimensional magnetic resonance imaging
Time frame: Baseline, post-1st chemotherapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pathologic Response to Chemotherapy | Tumor Volume | Baseline | 22.0 cm3 | Standard Deviation 18.7 |
| Pathologic Response to Chemotherapy | Tumor Volume | Post-1st chemotherapy | 11.0 cm3 | Standard Deviation 13.2 |
| Non-pCR | Tumor Volume | Baseline | 38.9 cm3 | Standard Deviation 89.8 |
| Non-pCR | Tumor Volume | Post-1st chemotherapy | 26.4 cm3 | Standard Deviation 44.4 |