title: Gamma probe and ultrasound guided fine needle aspiration cytology of the sentinel node (GULF) trial - overview of the literature, pilot and study protocol.
abstract: Sentinel node (SN) biopsy (SNB) detects clinically occult metastases of breast cancer and melanoma in 20-30%. Wound infections, seroma and lymph edema occur in up to 10%. Targeted ultrasound (US) of the SN, (with fine needle aspiration cytology (FNAC) if appropriate) has been investigated as a minimally invasive alternative, but reported sensitivity rates are too low to replace SNB. Our hypothesis is that the use of a handheld gamma probe concomitant with US may improve sensitivity. Our aim is to provide an overview of the current literature on preoperative nodal staging of clinical N0 melanoma patients, report on a pilot, and present a study protocol for a minimally invasive alternative to the SNB: Gamma probe and Ultrasound guided Fine needle aspiration cytology of the sentinel node (GULF trial).
  
  
  
  The GULF trial is a multicenter open single arm observational trial. Newly diagnosed cT1b-4N0M0 cutaneous melanoma or cT1-3N0M0 breast cancer patients, aged >18 years, presenting for SNB are eligible. 120 patients will be included for preoperative targeted gamma probe guided US and FNAC of the SN. Afterwards all patients proceed to surgical SNB. Primary endpoint is the sensitivity of FNAC. Secondary endpoints include SN identification rate and the histopathological compatibility of Core Needle Biopsy and FNAC vs. SNB. Secondary endpoints were investigated in a pilot with 10 FNACs and marker placements, and 10 FNACs combined with Core Needle Biopsy.
  
  
  
  A pilot in 20 patients showed that SN identification rate was 90%, supporting the feasibility of this technique.
  
  
  
  There is broad experience with US (in combination with FNAC) prior to SNB, but sensitivity and specificity are too low to completely abandon SNB. Promising alternative techniques potentially will replace SNB in the future but more evidence is needed in the form of prospective studies. Accurate identification of the SN for US-FNAC has been proven feasible in our pilot. When adequate sensitivity can be reached, US-FNAC provides a minimally invasive alternative for the surgical SNB procedure.
  
  
  
  The GULF trial is registered in the Netherlands Trial Registry (NTR), ID: NRT5193 . May 1st 2015.
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075, Rotterdam, EA, The Netherlands. c.oudeophuis@erasmusmc.nl.
authors.forename: Charlotte M C
authors.initials: CMC
authors.lastname: Oude Ophuis
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075, Rotterdam, EA, The Netherlands.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Koppert
authors.affiliation: Department of Radiology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075, Rotterdam, EA, The Netherlands.
authors.forename: Cécile
authors.initials: C
authors.lastname: de Monyé
authors.affiliation: Department of Pathology, Erasmus Medical Center, Wytemaweg 80, 3015, Rotterdam, CN, The Netherlands.
authors.forename: Carolien H M
authors.initials: CHM
authors.lastname: van Deurzen
authors.affiliation: Department of Pathology, Erasmus Medical Center, Wytemaweg 80, 3015, Rotterdam, CN, The Netherlands.
authors.forename: Senada
authors.initials: S
authors.lastname: Koljenović
authors.affiliation: Department of Surgical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066, Amsterdam, CX, The Netherlands.
authors.forename: Alexander C J
authors.initials: ACJ
authors.lastname: van Akkooi
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075, Rotterdam, EA, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075, Rotterdam, EA, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Grünhagen
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration / Q000295:instrumentation* / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005720:Gamma Rays; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000473:pathology*; D009367:Neoplasm Staging; D010865:Pilot Projects; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy / Q000295:instrumentation*; D012878:Skin Neoplasms / Q000473:pathology*
keywords: Breast Neoplasms; Fine-needle biopsy; Melanoma; Minimally invasive surgical procedures; Sentinel lymph node biopsy; Ultrasonography