SLNB IN CUTANEOUS MELANOMA: VALIDATION OF ITS INTRAOPERATIVE DETECTION THROUGH SPIO IMINEM STUDY

Transcription

1 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

2 PROGNOSTIC FACTORS OF CUTANEOUS MELANOMA Classic TNM TNM + ulceration + mitotic index N Number of affected lymph nodes Tumor load (micrometastasis macrometastasis) Controversy of the utility of elective lymphadenectomy versus therapeutic lymphadenectomy.

3 SLNB Location of drainages. Detection of lymph node(s). Avoid morbidity associated with lymphadenectomy. Prognostic utility?

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6 Ann Surg Oncol Oct;21(11): Unmatched Matched

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8 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.

9 IMINEM INTRODUCTION: new method The company Endomagnetics has developed a non-radioactive method to identify the sentinel lymph node using a superparamagnetic ironoxide (SPIO) tracer called Sienna+ and a manual magnetometer called SentiMag.

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13 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).

14 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.

15 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.

16 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,...).

17 SAMPLE SIZE Power of 80%, 95% CI (5% alpha error), Proportion of discordant pairs: % of losses 186 patients Non-inferiority design Competitive recruitment after minimal inclusion

18 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: H 0 : p S p E 0.05 H 1 : p S p E < 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.

19 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.

20 PROTOCOL (II) After 20 minutes: transcutaneous measurement with SentiMag Valuing territories (lymphoscintigraphy information?) Surgical identification: o 1 st SentiMag o 2 nd gamma detection probe PLASTIC MATERIAL INSTRUMENTS Ex vivo check and HRD record SLN analysis (deferred)

21 TC99 injection 1 day before General anaesthesia Sienna+ injection at least 20 min before the SLNB +/- colorant injection Patient preparation SLN localization Incision Transcutaneous localization gamma probe Transcutaneous localization SentiMag SLN extraction Data analysis SLN diagnosis Statistics

22 DATA COLLECTION SHEET

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24 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-necktrunk versus concordance between the cases with location of the melanoma in the limbs.

25 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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