slnb in cutaneous melanoma: validation of its intraoperative detection through spio ·...
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SLNB IN CUTANEOUS MELANOMA: VALIDATION OF ITS INTRAOPERATIVE
DETECTION THROUGH SPIO
IMINEM STUDY
Antonio Piñero-Madrona MD PhD
Hospital Clínico Universitario “Virgen de la Arrixaca” Murcia
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PROGNOSTIC FACTORS OF
CUTANEOUS MELANOMA
• “Classic” TNM
• TNM + ulceration + mitotic index
NNumber of affected lymph nodes
“Tumor load” (micrometastasis – macrometastasis)
Controversy of the utility of elective lymphadenectomy
versus therapeutic lymphadenectomy.
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SLNB
• Location of drainages.
• Detection of lymph node(s).
• Avoid morbidity associated with
lymphadenectomy.
• Prognostic utility?
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Unmatched
Matched
Ann Surg Oncol. 2014 Oct;21(11):3377-85
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IMINEM
INTRODUCTION: current status
• Combined technique as gold standard to perform SLNB. Isotope
essential:
o Need for prior lymphoscintigraphy.
o Exposure to radiation.
o Periods of latency (controversies).
o Colorant disadvantages:
• Allergic reactions.
• Distortion by “spotting” of the field.
• Residual stains at the injection site.
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• The company Endomagnetics has developed a non-radioactive method
to identify the sentinel lymph node using a superparamagnetic iron-
oxide (SPIO) tracer called Sienna+® and a manual magnetometer
called SentiMag®.
IMINEM
INTRODUCTION: new method
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AIMS
• Primary: To assess the equivalence of the Endomagnetics
SentiMag®/Sienna+® system with the technique currently used in
routine for the detection of the sentinel lymph node in patients with
cutaneous melanoma.
• Secondary: To check the concordance in cases with a different site of
location of the primary tumor (trunk-head-neck vs limbs).
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STUDY TYPE
• Non-EPA observational study (consult AEMPS).
• Approval by the Ethical Committee of reference (HCUVA).
• It requires approval by the corresponding local Ethical
Committee.
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INCLUSION CRITERIA
• Adult patients (>18 years of age),
• with diagnosis of cutaneous melanoma and
• in which SLNB is indicated as a staging method, and
• with cN0 result after clinical-echographic-cytohistological
evaluation.
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EXCLUSION CRITERIA
• Previous treatment with systemic therapy.
• Recent previous surgery (<3 months) in the area susceptible of lymphatic
drainage from the melanoma.
• Intolerance or hypersensitivity to iron or dextran compounds.
• Impossibility of use of radioisotope.
• Existence of pathology related to elevation of organic iron (hemosiderosis,
hemochromatosis, iron deficiency anemia of metabolic or circulatory
origin).
• Implantation of pacemakers or partially or totally metallic thoracic
implants.
• Treatment with iron chelators (deferasirox, deferoxamine, ...).
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SAMPLE SIZE
• Power of 80%,
• 95% CI (5% alpha error),
• Proportion of discordant pairs: 0.05
• 10% of losses
186 patients
Non-inferiority design
Competitive recruitment after minimal inclusion
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STATISTICS
• The main analysis aims to demonstrate the non-inferiority of the new or experimental technique (E) with respect to the standard technique (S), with a limit of non-inferiority of 0.05 (or 5%), and will consist of proposing the following hypothesis test:
H0: pS – pE ≥ 0.05H1: pS – pE < 0.05
• It is a unilateral test, in which pS and pE represent the proportions of patients in whom sentinel node(s) was detected with standard and new technique, respectively. The test will be performed with significance level a=0.05.
• To perform the test, all valid patients will be used, that is, patients who meet the study selection criteria and have the necessary data for the analysis of the main objective.
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PROTOCOL (I)
• Injection of the isotopic tracer in standard form (intradermal;
perilesional / pericicatricial; "centrifugal") and in the usual
preoperative period (hours-day).
• Identical injection in three-four punctures of 2 mL of Sienna+ ®
diluted (saline) up to a total of 5 mL. Local massage of 5-10 minutes.
• Optional: colorant injection in standard form. Local massage of 5-10
minutes.
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PROTOCOL (II)
• After 20 minutes: transcutaneous measurement with SentiMag®
• Valuing territories (lymphoscintigraphy information?)
• Surgical identification:
o 1st SentiMag®
o 2nd gamma detection probe
• PLASTIC MATERIAL INSTRUMENTS
• Ex vivo check and HRD record
• SLN analysis (deferred)
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TC99 injection1 day before
General anaesthesia
Sienna+ injection at least 20 min before
the SLNB +/-colorant injection
Patient preparation
Transcutaneous localizationSentiMag
Transcutaneous localization
gamma probeIncision
SLN localization
SLN extraction Data analysis SLN diagnosis Statistics
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DATA COLLECTION SHEET
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ANALYSIS
• Relative efficacy of the procedure through study of proportion of
sentinel lymph nodes detected with the two methods.
• Percentage of concordance in the detection (by patient and lymph
node). Each case acts as its own control.
• Concordance between the cases with tumor located in head-neck-
trunk versus concordance between the cases with location of the
melanoma in the limbs.
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Participating Centers
• Hospital Clínico Universitario “Virgen de la Arrixaca”. Murcia.
• Hospital Universitario “Ramón y Cajal”. Madrid.
• MD Anderson Cancer Center. Madrid
• Hospital Clínic. Barcelona.
• Instituto Valenciano de Oncología.
• Hospital General Universitario “Reina Sofía”. Murcia.
• Hospital General Universitario de Ciudad Real.
• Hospital “Nuestra Señora del Prado”. Talavera de la Reina.
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