To determine whether [18F]FES PET/CT improves staging for women with clinical stage II/III or LRR, ER+ breast cancer as compared to standard [18F]FDG PET/CT.
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1) Percentage of patients with a correctly changed treatment plan according to
information obtained with [18F]FES PET/CT compared to [18F]FDG PET/CT at
staging.
2) Percentage of metastatic lesions detected with [18F]FES PET/CT compared to
[18F]FDG PET/CT at staging.
3) Percentage of missed metastases with [18F]FES PET/CT compared to [18F]FDG
PET/CT (at staging and developed during follow-up).
4) Percentage of correct treatment plans as well as diagnostic confidence after
6 months of follow-up as determined by the adjudication committee based on the
added information obtained with [18F]FES PET/CT compared to [18F]FDG PET/CT.
Secondary outcome
1) The relationship between the level of [18F]FES/[18F]FDG uptake in the
primary tumor, lymph node and distant metastases and standard (size, location
of lesion, histological subtype, grade, ER/PR/HER2 expression levels,
Ki67%/mitotic index)/experimental clinicopathological parameters (intensity of
ER staining, tumor cell and microvessel density, infiltration of lymphocytes,
amount of necrosis and stroma, expression of glucose
transporter-1 (GLUT1) of the primary tumor, lymph node and distant metastases).
2) Cut off value for [18F]FDG SUV (max and peak) below which [18F]FES PET/CT
adds information for staging.
3) Cut off value for grade and ER expression level below which or above which,
respectively, [18F]FES PET/CT adds information for staging.
Background summary
Accurate staging is of great importance in patients with clinically locally
advanced primary breast cancer (LABC, stage III) or locoregional recurrent
(LRR) breast cancer for making a correct treatment plan. According to current
guidelines, staging is performed with positron emission tomography (PET) using
the 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET tracer, combined with
diagnostic computed tomography (CT). However, previous studies have shown that
this technique (with the current PET tracer) might not be sufficient for
accurate staging. Specifically in low grade, estrogen receptor positive (ER+)
breast cancer metastases can be missed due to the low metabolic activity,
leading to low uptake of [18F]FDG. Therefore, there is a clinical need to
improve staging procedures. 16α-[18F]-fluoro-17β-estradiol ([18F]FES), an
ER-targeted PET tracer, allows imaging of ER+ tumor lesions regardless of their
metabolic activity. Patients with clinically LABC and LRR have a 25-50% risk of
distant metastases. Correct identification of distant metastases allows
adaptation of the treatment plan to avoid burdensome treatment with surgery,
systemic and radiotherapy in order to maintain quality of life. In case of
oligometastases, correct identification increases the likelihood for cure with
local treatment. In the current study we will compare disease staging with
[18F]FES- and [18F]FDG PET in patients with clinical stage II/III or LRR breast
cancer.
Study objective
To determine whether [18F]FES PET/CT improves staging for women with clinical
stage II/III or LRR, ER+ breast cancer as compared to standard [18F]FDG PET/CT.
Study design
In this multicenter observational study with invasive measurements, patients
with clinically ER+ clinical stage II/III and LRR breast cancer will be
included. All patients will undergo the current *standard* diagnostic
procedures including a histological biopsy of the primary tumor, cytology of
axillary lymph nodes and imaging procedures with mammography, ultrasound of
breast and axilla, magnetic resonance imaging (MRI) breast and whole body
[18F]FDG PET combined with diagnostic chest/abdominal CT. The histological
and/or cytological biopsies will be performed before or more than 4 days after
the [18F]FDG PET/CT scan to avoid biopsy related [18F]FDG uptake. The
*experimental* imaging procedure with [18F]FES PET/CT will be performed within
21 days before or after the [18F]FDG PET/CT with at least a 24 h interval
between both tracer administrations to allow for sufficient decay.
After evaluation of the obtained scans, an *experimental histological biopsy*
of a lymph node metastasis will be obtained and clinically relevant [18F]FDG+
and/or [18F]FES+ lesions and/or suspicious lesions on CT will be biopsied
according to standard clinical practice for pathological analyses. New
(experimentally) identified and pathologically confirmed metastases will be
included in the subsequent treatment plan. The standard follow-up will take
place every 3 months for a time period of 24 months after diagnosis to detect
potentially missed metastases. At 6 months of follow-up, the treatment plan
will be evaluated by an independent committee (surgeon, medical oncologist and
nuclear physician/radiologist). We expect to include the total number of
patients (40 patients) in 18 months.
Study burden and risks
Patients will receive an intravenous cannula for tracer injection and blood
sampling, causing potentially transient discomfort at the site of the cannula
insertion. Tumor biopsy will be performed from an easy accessible lesion and
the most frequent complications that can occur are discomfort, bleeding and
(local) infection. The risk of complications from a tumor biopsy is considered
low: 0.24-1.6% and 0.11-0.48% for major complications and mortality,
respectively. Radiation exposure from a [18F]FES PET and [18F]FDG PET scan
usually ranges between 4-11 mSv and 7-8 mSv, respectively. Radiation exposure
from a diagnostic CT scan ranges between 8-14 mSv. The total radiation burden
is considered justifiable when compared to the information that can be obtained
from this study, in this patient group with breast cancer.
For the [18F]FES PET scan: patients will be asked to fast for 4 hours prior to
the scan.
Imaging with [18F]FES PET may improve staging for patients with breast cancer
as it may show tumor lesions that could not be identified with [18F]FDG PET,
the current standard for staging. If this is the case, the initial treatment
goal and intensity can be adjusted which can have beneficial effects for the
patient.
De Boelelaan 1118
Amsterdam 1081 HV
NL
De Boelelaan 1118
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Clinical stage II/III or locoregional recurrent breast cancer (all
histological types) with ER+ and low grade according to Bloom Richardson
criteria (grade 1-2)
- Females aged 18 years or older at screening
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
- Candidates for treatment with curative intent (patients are also allowed for
inclusion in the current study if they have undergone recent surgery (<6 weeks)
for current breast cancer and require staging because of unexpected stage III
disease)
- [18F]FDG PET/CT imaging should be performed for staging according to standard
of care (in case [18F]FDG PET/CT imaging has already been performed, patients
can be included <=21 days after this scan)
- Estimated glomerular filtration rate (eGFR) >=30 ml/min
- Written and signed informed consent
Exclusion criteria
- History with another cancer within the last 5 years, except non-melanoma skin
cancer
- Undergoing treatment for current breast cancer such as (neo)adjuvant
chemotherapy, hormonal therapy (only in case of Tamoxifen), radiotherapy or
investigational drug therapy
- Pregnancy or lactating women
- Any medical, psychological or social condition that may interfere with the
subject*s safety and participation in the study, will lead to exclusion from
this study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-002013-35-NL |
| CCMO | NL66099.029.18 |