We propose to use an alternative superparamagnetic tracer containing ironoxide, which can be detected with MRI and with a magnetic probe. The spatial resolution of MRI is superior to gamma camera detection. Moreover, there is no radiation exposure…
ID
Source
Brief title
Condition
- Metastases
- Head and neck therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter is the diagnostic accuracy, in terms of sensitivity
and negative predictive value, of a complete magnetic SLNB procedure (SPIO
peritumoral injections, preoperative SPIO-enhanced MRI and SLN harvesting using
a magnetometer) and the additional value of the magnetic SLNB procedure to the
radioactive (conventional) SLNB. Results of the complete magnetic SLNB will be
evaluated and compared with the reference standard, i.e. histopathological
examination of SLNs and complementary neck dissection specimens as well as 12
months follow-up.
False-negative SLNB outcomes of included patients will be scored.
False-negative rates (false-negative/(false-negative + true-positive))
following each SLNB technique and the combination will be calculated and
presented in percentages. If a positive SLN is missed by one of the techniques
(but depicted by the other technique) this SLN is considered false-negative for
this technique. Using the false-negative rates, the sensitivity
(true-positive/(true-positive + false-negative)) and NPVs
(true-negative/(true-negative + false-negative)) will be calculated accordingly
for each technique separately and combined.
Secondary outcome
Detection rate (in percentages) of SLN(s) with SPIO-enhanced MR
lymphoscintigraphy as compared to conventional lymphoscintigraphy using
99mTc-nanocolloid with histopathology as the reference standard as well as 12
months follow-up.
The number of SLNs identified for each subject will be recorded, and summary
statistics (mean, median, standard deviation, minimum, and maximum) on the
number of SLNs will be displayed.
The pathological status of SLNs will be assessed on a per subject basis. The
number and percentages of subjects who have at least one
histopathological-positive SLN will be calculated.
Background summary
Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that has
been implemented as Dutch standard oncological care for several tumor types,
including early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC). An
infamous limitation of the routine SLNB procedure arises in situations where
sentinel lymph nodes (SLN) are located in close vicinity of the radioactive
tracer injection site. In these cases, due to the limited resolution of the γ-
camera and SPECT, the hotspot of the tracer injection site can hide adjacent
SLNs, which consequently hampers discrimination between tracer injection site
and SLNs. This shine-through phenomenon is particularly evident in
floor-of-mouth (FOM) OSCC, resulting in a significantly lower accuracy of SLNB
in FOM tumors (sensitivity 63%; NPV 90%) compared to other oral cavity subsites
(sensitivity 86%; NPV
95%).
A lower accuracy for SLNB can result in abandonment of occult lymph node
metastasis, by erroneously staging the neck as negative for metastases, which
will inevitably develop into clinical manifestation of disease and consequently
harbors a poor oncological prognosis.
Study objective
We propose to use an alternative superparamagnetic tracer containing ironoxide,
which can be detected with MRI and with a magnetic probe. The spatial
resolution of MRI is superior to gamma camera detection. Moreover, there is no
radiation exposure and no dependency on complex radioisotope production and
transport infrastructure with this alternative.
The non-inferiority of superparamagnetic compared to radioactive tracers has
already been proven in breast cancer. It is not clear if results obtained in
breast cancer can be translated to oral cancer, because of its complex
lymphatic drainage pattern and higher lymphatic flow. Two studies showed that
preoperative identification of SLNs in oral cancer patients with a magnetic
tracer on MRI lymphography corresponded with radioisotope tracer identification
on lymphoscintigraphy. A recent feasibility study showed that SLNs with
superparamagnetic particles of ironoxide (SPIO) could be identified
intraoperatively by means of a magnetic probe after peritumoral injections of
these SPIO particles. In another recent study we confirmed the feasibility to
detect SLNs with SPIO nanoparticles intraoperatively and optimized the protocol
of preoperative MRI visualization and intraoperative
detection for tracer dose and interval between injection and imaging. Combining
the results of both studies revealed a sensitivity of 80% (4/5) and a negative
predictive value of 93% (14/15), using routine histopathological examination of
the elective neck dissection specimen as reference standard. Of note, 42%
(8/19) of these patients had OSCC located in the FOM.
Study design
This study is designed as a prospective Dutch multicenter cohort study. A total
of 82 patients with early-stage OSCC (cT1-3N0M0), scheduled for transoral tumor
resection and SLNB, will be included in a multicenter study to evaluate
SPIO-enhanced MRI and intraoperative detection of magnetic particles by
magnetometer for SLNB. Following inclusion, participants will undergo both
conventional (standard) lymphoscintigraphy and SPECT-CT after peritumoral
administration of [99mTc]-nanocolloid as well as SPIO-enhanced MRI after
peritumoral administration of superparamagnetic iron oxide nanoparticles.
Paired images of each patient (i.e. [99mTc]-nanocolloid lymphoscintigraphic
images including SPECT-CT and SPIO nanoparticles MR images) will be evaluated
with regard to similarity of depicted draining lymph node basins, number and
location of SLNs and their histopathological outcome. During surgery SLNB will
be first performed using the magnetometer (harvested SLNs will also be measured
by gamma probe) by surgeon A (blinded for lymphoscintigraphy results) and
thereafter using the gamma probe for eventual remaining SLNs in the neck by
surgeon B (lymphoscintigraphy report available and/or discussed with the
nuclear physician).
Results of the complete magnetic SLNB will be evaluated and compared with the
reference standard, i.e. histopathological examination of SLNs and
complementary neck dissection specimens as well as 12 months follow-up.
False-negative SLNB outcomes of included patients will be scored. Accordingly,
the diagnostic accuracy (i.e. sensitivity, negative predictive value) of both
sentinel node biopsy methods only and the combination will be calculated and
compared. Intranodal appearance on SPIO-enhanced MRI will be correlated to
detailed histopathological examinations of the resected SLN. Although not
included in this research project, due to time limitations, included patients
will be asked for participation in a long-term follow-up study, with at least
two years follow-up.
Intervention
The study population will receive peritumoral injections of superparamagnetic
iron oxide nanoparticles (SPIO) and afterwards a pre-operative MRI lymphography
will be performed to locate the sentinel nodes. On the day of surgery, or the
day before, pre-operative MRI lymphography will be performed. First, the
sentinel node extirpation will be performed with the magnetometer (Sentimag).
Afterwards, the surgery will proceed according to standard protocol.
Study burden and risks
Patients will undergo additional peritumoral injections (i.e. SPIO 0.4 mL) and
MRI lymphography with an estimated duration of 30 minutes. Besides irritation
or pain at the injection site, adverse reactions after injection of SPIO rarely
occur. Besides, there is substantial experience in the use of SPIO in breast
cancer. No interactions between 99mTc-radiotracers and SPIO that might harm the
patient are known. Magnetic SLNB may result in harvesting additional SLNs, not
detected by conventional radioactive SLNB. Resection of additional SLNs,
expected mainly close to the injection site (generally in level I of the neck),
may have complications, but are rare in this procedure. However, harvesting
these SLNs, which can be missed by conventional lymphoscintigraphy and SPECT-CT
(false-negative outcome), provides better staging of the nodal basin.
Abandonment of occult lymph node metastasis, especially if this has therapeutic
consequences in context of SLNB, will inevitably result in clinical
manifestation of disease, resulting in more extensive treatment (more often
modified radical neck dissection and adjuvant radiotherapy) and a worse
oncological prognosis. A slight prolongation of operation room time is
expected, however operation risks are practically not increased. Therefore, we
conclude the risk is negligible for this study according to the NFU-guidelines.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
1. The patient has provided written informed consent authorization before
participating in the study.
2. The patient has a diagnosis of primary oral squamous cell carcinoma that is
anatomically located in: mucosal lip, buccal mucosa, lower alveolar ridge,
upper alveolar ridge, retromolar gingival (retromolar trigone),
floor-of-the-mouth, hard palate or oral (mobile) tongue, and is stage cT1-T2
and T3 (only when T3 is assessed based on tumor dimensions of >2 cm and <=4 cm
with DOI >10 mm) (see Appendix 3: Tumor Nodal Metastasis (TNM) Staging).
3. Clinical nodal staging (cN0) has been confirmed by at least ultrasound, with
in case of suspicious lymph nodes ultrasound guided fine-needle aspiration
cytology, CT and/or MRI within 30 days of the SLNB procedure.
4. The patient is a candidate for transoral excision.
5. Patients with prior malignancy of the head and neck area are allowed,
provided the patient meets both of the following criteria:
a. Underwent potentially curative therapy for all prior head and neck
malignancies and is deemed low risk for recurrence; and
b. No head and neck malignancy for the past three years and no evidence of
recurrence.
6. The patient is >=18 years of age at the time of consent.
7. The patient has an ECOG status of Grade 0 - 2 (see Appendix 4: Performance
Status Criteria).
Exclusion criteria
1. The patient has a diagnosis of squamous cell carcinoma of the head and neck
in the following anatomical areas: non-mobile base of the tongue, oropharynx,
nasopharynx, hypopharynx, and larynx.
2. The patient has clinical or radiological evidence of metastatic cancer to
the regional lymph nodes.
3. The patient has a history of neck dissection, or gross injury to the neck
that would pre-clude reasonable surgical dissection for this trial, or
radiotherapy to the neck.
4. The patient is incapacitated.
5. The patient has had an intolerance or hypersensitivity to iron or dextran
compounds, Magtrace® or lidocaine.
6. The patient has an iron overload disease.
7. The patient has an active implantable device in the upper body.
8. The patient is known with claustrophobia, who are a consequence unable to
undergo MR imaging.
9. The patient has a contra-indication for MR imaging (e.g. metal implant).
10. The patient is pregnant.
11. Participation will result in unacceptable delay regarding oncological
treatment.
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
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In other registers
| Register | ID |
|---|---|
| CCMO | NL81165.041.22 |