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

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.

SLNB

• Location of drainages.

• Detection of lymph node(s).

• Avoid morbidity associated with

lymphadenectomy.

• Prognostic utility?

Unmatched

Matched

Ann Surg Oncol. 2014 Oct;21(11):3377-85

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.

• 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

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).

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.

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.

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, ...).

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

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.

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.

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)

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

DATA COLLECTION SHEET

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.

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.