Non-invasive nodal staging in breast cancer with MRI Lymphography using gadofosveset.

Lymph node status is one of the most important prognostic factors in breast
cancer and is of particular value in choosing
adjuvant therapy. About 30% of breast cancer patients have histopathologically
positive axillary lymph nodes.
Nowadays, all breast cancer patients undergo a mammography, breast ultrasound,
histology, and a breast MRI. After the
diagnosis breast cancer has been determined, the current nodal staging consists
of an axillary ultrasound and possible
cytologic or histologic punction followed by sentinel lymph node biopsy (SLNB)
and/or an axillary lymph node dissection
(ALND). After introduction of the MRL, first the accuracy has to be
established. If MRL is equally accurate to the current
nodal staging workup, skipping partly the SLNB and its histology might make
this workup more efficient. So, accuracy will be researched by comparing the
current, invasive, nodal-staging with noninvasive MRL in relation to the golden
standard, histological examination of the SLNB and/or ALND.
In addition, MRL might be able to detect extra-axillary lymph node metastases
which could induce a change in treatment
regimen for an unknown number of patients. Studies on a positive parasternal
SLNB show a change in adjuvant treatment
in 0.9% of the patients. Furthermore, it is known that the SLNB has a false
negative rate of 9.8%. In this pilot study we will
only investigate the axillary region with MRL. We know that a possible reason
for a false negative SNLB is a low number
of specimens removed during the SLNB procedure. MRL might be able to detect the
nodes missed by SLNB.

The aim of this pilot-study is to examine the accuracy of MRL compared to
current nodal staging methods. We expect an
acceptable accuracy of the MRL based on earlier studies with gadofosveset
enhanced MRI in rectum cancer patients. Then the MRL could indicate a tailored
made treatment possible. It is unlikely that the MRL can replace all SLNB*s
considering the fact that it might not be able to detect nodal metastases
smaller than 0.2mm. Detection of these metastases is crucial since they change
adjuvant treatment regimen.

This study is designed as a single-center prospective cohort study. We plan to
include 160 patients in this pilot-study.
Patients will be recruited in the Maastricht Universitair Medisch Centrum
(MUMC). We expect a period needed to recruit of 15 months.
Patients will undergo an axillary MRI with gadofosveset contrast agent. With
the MRI and coils used in this study we only investigate the axilla on the site
of the breast cancer.
The accuracy of MRL will be determined on the basis of a node-to-node matching
of imaged nodes to the definitive
histopathology. The pathologic examination of the SNLB or ALND will be regarded
as the golden standard for nodal
involvement. The pathologic examination will take place following the regular
procedure. During microscopic examination each node will
be recorded as benign, or isolated tumor cell (ITC) ( pN0(i+) ) (* 0.2mm ), or
micrometastase (pN1mi) (0.2 * 2.0mm) or
macrometastase (pN1) (>2.0mm).
Overall nodal status will be reported following the regular procedure. With
this result we can make the patient by patient
analysis.
The results of the pathologic examinations will be compared to the results of
the MRL. The MRL will be assessed by two
radiologists, who will independently read all the images and they are blinded
for earlier investigations. In the meantime
they will receive feedback about the pathologic results, in order to make a
learning curve possible.
Each lymph node visible on MRL will be scored as benign or malignant using a
confidence level score (0= definitely
benign, 1= probably benign, 2= possibly benign, 3= probably malignant, and 4=
definitely malignant). Criteria for
malignancy on gadofosveset-MRI will be low signal intensity and absence of a
*relief* sign.
The diagnostic performance of gadofosveset-MRI will be analyzed on lesion by
lesion basis and on patient by patient
basis. In this way we can obtain precise validation of imaging findings with
the underlying histopathology. The lesion by
lesion results will be translated to a patient by patient validation in order
to obtain a clinically more relevant assessment of
the diagnostic performance on a patient basis.

MRI of the lymph nodes in the axilla with gadofosveset contrast agent.

The patient who participates in this study will undergo all regular
investigations to come to a proper staging of the breast
cancer. The current procedure on staging of breast cancer patients is
extensive. The procedure includes in most cases a
MRI scan of the breast. For this study we will perform an extra MRI with
gadofosveset contrast agent of the axilla a couple of days after the initial
MRI scan. Further investigation needed for this study will not extra burdensome
the patients, because all further procedures are already included in the
regular treatment.