pet/ct in breast cancer · without clinical symptoms. fdg pet in this scenario is more accurate...
TRANSCRIPT
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PET/CT in Breast Cancer
Rodolfo Núñez Miller, M.D.
Nuclear Medicine and Diagnostic Imaging Section
Division of Human Health
International Atomic Energy Agency
Vienna, Austria
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Overview
Introduction
Locorregional staging
Distant (Sistemic) staging
FDG PET in skeletal metastasis
Monitoring response to neoadjuvant therapy
Monitoring response to metastatic disease
Positron Emission Mammography (PEM) and BSGI
Metabolic Flare
Future directions: molecular imaging
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Breast Cancer
Is the second leading cause of cancer mortality in
women.
Although the incidence continues to rise, mortality has
declined over the past several years.
This decline has been attributed to both, early diagnosis
and more effective treatment.
Advances in molecular cancer biology, are bringing a
better understanding of breast cancer pathogenesis and
progression, which translates into new and effective
treatments.
Personalized target therapy.
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Locoregional Staging with FDG
PET/CT
There is currently no clinical role for routine FDG PET/CT
axillary staging in women with newly diagnosed breast
cancer.
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Locoregional Staging with FDG
PET/CT in patients at high risk for
nodal disease FDG PET is highly specific for axillary nodal metastases.
There may be a certain role for preoperative FDG PET/CT in certain
patient populations, such as LABC, IBC, plexopathy and
symptomatic metastasis.
In these cases, if confirmed by PET, US guided tissue sampling of
abnormal findings can confirm the diagnosis.
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FDG PET of the Internal Mammary
Nodes
Is seen in approximately 25% of patients with LABC.
Is predictive of both, likelihood and pattern of treatment failure,
consistent with IM nodal disease involvement and progression.
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PET/CT in Inflammatory Breast
Cancer (IBC) Study by Carkaci et al., demonstrated that in newly diagnosed
unilateral IBC (n=41), FDG PET/CT was positive for ipsilateral
axillary nodal involvement in 90%, ipsilateral subpectoral nodes in
44%, and distant metastasis in 49% (17% unknown before PET/CT).
FDG PET/CT should be considered in the initial staging of IBC.
Carkaci et al. JNM 2009; 50: 231-238
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Retrospective Analysis of 18F-FDG PET/CT for Staging
Asymptomatic Breast Cancer Patients Younger Than 40
Years. Riedl CC et al. JNM October 2014
PET/CT revealed distant metastases in 17% of asymptomatic stage IIB breast cancer
patients younger than 40 y.
Although guidelines of the National Comprehensive Cancer Network recommend
against systemic staging in patients with stage II disease, our data suggest that PET/CT
might be valuable in younger patients with stage IIB and III disease.
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PET/CT revealed distant metastases in 17% of asymptomatic stage IIB breast cancer
patients younger than 40 y.
Although guidelines of the National Comprehensive Cancer Network recommend
against systemic staging in patients with stage II disease, our data suggest that PET/CT
might be valuable in younger patients with stage IIB and III disease.
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Distant (Systemic) Staging with
FDG PET
Current NCCN practice guidelines, recommend FDG
PET as an option for patients with stage 4 disease. In
this setting it has been shown to be both, sensitive and
specific.
FDG PET can be particularly helpful in identifying occult
sites of disease; thus affecting therapeutic options.
FDG PET or PET/CT can reveal in this setting unknown
metastasis in locoregional and mediastinal nodal basins,
which are not obtimally evaluated by conventional
imaging.
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39 year old woman with left breast cancer, treated with surgery (Febr,
2010) followed by chemo. There is known liver involvement. Referred
for re-staging after initial therapy.
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Systemic Staging with FDG PET
FDG PET and PET/CT can improve staging and alter therapeutic options in patients suspected to have recurrent breast cancer and distant metastatic disease.
FDG PET can change or affect treatment in up to 44% of patients suspected to have locorregional recurrence.
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43 year old woman with left breast cancer, treated initially with surgery,
followed by chemo and RT during 2008. PET/CT requested to re-stage
after initial therapies.
October 2009
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43 year old woman with left breast cancer, treated initially with surgery,
followed by chemo and RT during 2008. PET/CT requested to re-stage
after initial therapies.
October 2009
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She gets treated with additional chemo. PET/CT is requested 6 months
later to assess response to therapy.
April 2010
October 2009
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She gets treated with additional chemo. PET/CT is requested 6 months
later to assess response to therapy.
October 2009
April 2010
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Staging with FDG PET and
PET/CT: When does it help? Is not recommended for routine staging of breast cancer.
FDG PET can provide additional information in staging or re-staging
cases when results of conventional imaging are equivocal or
conflicting.
Evaluating asymptomatic patients with rising serum tumor markers
without clinical symptoms. FDG PET in this scenario is more
accurate than conventional imaging. In a recent study* FDG PET/CT
was 90% sensitive for diagnosing recurrent tumor, affecting clinical
management in 51% of patients.
* Randan L et al. Cancer 2006; 107(11):2545-2551
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54 year old woman with breast cancer. Referred for re-staging
purposes.
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FDG PET and PET/CT of Skeletal
Metastases
FDG PET is complementary to bone scintigraphy, which remains
the standard imaging modality for surveying the skeleton for
metastatic disease.
FDG PET better for osteolitic. BS better for osteoblastic.
In the “future” F18 Fluoride PET may offer improve bone metastasis
detection compared to FDG and BS.
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FDG FDG Na18F Na18F
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Monitoring Response to Therapy
with FDG PET and PET/CT
Neoadjuvant
Metastatic Disease
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Monitoring response to
Neoadjuvant Therapy
Limitations of conventional anatomic imaging.
Neoadjuvant Therapy can improve surgical options and
provide prognostic information.
One of the main objectives is to assess response of the
primary tumor to the treatment regime.
Most studies measure the change in FDG uptake to mid-
therapy compared to baseline.
50% or more decline in FDG uptake.
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Monitoring response to
Neoadjuvant Therapy FDG PET may serve as an earlier predictor of response.
Absence of FDG uptake is not a reliable indicator of pCR.
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Dedicated Molecular Breast
Imaging Devices
PEM
BSGI
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BSGI
The concept – Greater access, close to chest
wall, able to image breast only
with no background activity
and scatter from surrounding
organs.
– Greater maneuverability
– Less intimidating
Enabling Technology – CZT detectors, low dead
space.
– Registered colimation
– Optimized pixel size
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Positron Emission Mammography
(PEM)
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The latest design allows for 12 tomographic slices and PEM directed
biopsies.
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Advantages in the detection with
PEM
• The advantages are:
- Greater spatial resolution.
- Improved geometric sensitivity.
- Shorter time of image acquisition.
- Less attenuation in comparison with PET
• Fairly small size, with possibility of doing biopsies directed by PEM.
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62 y-o IDC 2.4cm mass, PEM ratio 3.4,
0.6 cm satellite
RMLO LMLO Images of PEM cortesy of Dr. Javier Villanueva-Meyer
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57 y-o IDC unexpected 10 foci in L breast, index
lesion 2 cm, PEM ratio 3.7
RCC LCC
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RMLO LMLO
43 y old IDC + DCIS index lesion 1,7 cm. PEM
ratio 7.7 . Multifocal + cysts
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46 y-o IDC triple negative, R lumpectomy,
8 year FU in remission
RCC LCC
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Limitations of PEM
• False Negatives – Posterior Lesions
– Tale of the breast
– Precision IDC > ILC > DCIS
• False Positives – Recent Biopsy
– Fat necrosis
– Fibroadenoma
– Other benign lesions
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PEM as alternative to MR
Patients with doubtful / equivocal lesions,
which cannot be evaluated by MR
(claustrophobia, pacemakers, which
happens in approx. 15% of cases).
Assessment of response to Neoadjuvant
therapy.
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Monitoring Response to Metastatic
Disease
FDG PET can be particularly useful in this setting to evaluate the
response to systemic therapy , since conventional imaging is often
challenging in these cases (e.g. skeleton).
Changes in FDG can be prognostic.
Combination of FDG and Na-18F can be helpful to assess the
skeleton. However, Na-18F can also have a “flare response”.
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Metabolic flare
ER+ Tamoxifen
Transient increase in metabolic activity of breast cancer within 1 to 2 wks after starting tamoxifen
The increase is about +25% in responders while non responders have no change
Seen with FDG and FES
Dehdashty & Mortimer
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Metabolic Flare
Dehdashti et al. Eur J Nucl Med 1999. 26:51-56.
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Future Directions: Molecular
Imaging
Tumor Perfusion and Angiogenesis Imaging.
- 15Oxigen water, imbalance of metabolism and perfusion (high mb, and
poor perfusion) is associated with poor response and early relapse.
- Assess tumor neovasculature, PET probes (RGD peptides) bind to
integrins (α5β3) in neovessels
Tumor Receptor Imaging.
- 18Fluoro 17-β-estradiol (FES)
- 68Ga-labelled F(ab’)2 fragment of trastuzumab, measuring regional
HER2 expression in animal models.
Early Response Imaging.
- FLT. Lilkely to become important in the future.
- 124 I Annexin V for apoptosis.
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CONCLUSIONS
FDG PET and PET/CT have been shown to be most helpful in
staging recurrent or metastatic breast cancer, and in evaluating the
response of LABC and metastatic disease to treatment.
Emerging data support the use of FDG PET/CT in advance axillary
disease and evaluation of regional nodal spread in LABC.
Currently FDG and occasionally Fluoride PET are used in clinical
practice.
It is likely that future studies will benefit from tracers other than FDG,
for example FES and FLT.
As breast cancer diagnosis and therapy become increasingly
molecular and individualized, PET/CT imaging will play a
progressively more important role in breast cancer patient care.
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Thank You