title: Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.
abstract: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND).
  
  
  
  The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper.
  
  
  
  The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (<31%) or recommended (>31%).
  
  
  
  The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.
authors.affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. franco.difilippo@ifo.gov.it.
authors.forename: Franco
authors.initials: F
authors.lastname: Di Filippo
authors.affiliation: Ospedale di Latina, Latina, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Filippo
authors.affiliation: San Camillo, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ferrari
authors.affiliation: Az. Ospedaliera Universitaria Foggia, Foggia, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Antonetti
authors.affiliation: ASL, Prato, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Battaglia
authors.affiliation: ULSS 7 Pieve di Soligo, Pieve di Soligo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Becherini
authors.affiliation: Hospital Lluís Alcanyís, Xàtiva, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Bernet
authors.affiliation: Università of Piemonte, Vercelli, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
authors.affiliation: Hôpitaux de Lyon, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bouteille
authors.affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Buglioni
authors.affiliation: ULSS 7 Pieve di Soligo, Pieve di Soligo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Burelli
authors.affiliation: Hospital Universitario de La Ribera, Alzira, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cano
authors.affiliation: Centro Regionale Oncologico, Bari, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.affiliation: , San Donato, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Chiodera
authors.affiliation: Policlinico of Bari, Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cirilli
authors.affiliation: San Filippo Neri, Florence, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Coppola
authors.affiliation: San Filippo Neri, Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Drago
authors.affiliation: Humanitas Rozzano, Rozzano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
authors.affiliation: ASST Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Privato
authors.initials: P
authors.lastname: Fenaroli
authors.affiliation: Azienda Ospedaliera "Maggiore della Carità" di Novara, Novara, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Franchini
authors.affiliation: ASST Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gianatti
authors.affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: University of Bari, Bari, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Giardina
authors.affiliation: Eugene Marquis Cancer Center, Rennes, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Godey
authors.affiliation: Humanitas Gavazzeni, Bergamo, Italy.
authors.forename: Massimo M
authors.initials: MM
authors.lastname: Grassi
authors.affiliation: San Filippo Neri, Florence, Italy.
authors.forename: Giuseppe B
authors.initials: GB
authors.lastname: Grassi
authors.affiliation: Hampshire Hospitals NHS Foundation Trust, England, UK.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Laws
authors.affiliation: Centro Regionale Oncologico, Bari, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Massarut
authors.affiliation: University of Pisa, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Naccarato
authors.affiliation: Azienda Ospedaliero-Universitaria OO.RR. Foggia, Foggia, Italy.
authors.forename: Maria Iole
authors.initials: MI
authors.lastname: Natalicchio
authors.affiliation: University of L'Aquila, L'Aquila, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Orefice
authors.affiliation: I.R.C.C.S. L. Spallanzani, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Palmieri
authors.affiliation: Centro Regionale Oncologico, Bari, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Perin
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Roncella
authors.affiliation: Humanitas, Pisa, Italy.
authors.forename: Massimo G
authors.initials: MG
authors.lastname: Roncalli
authors.affiliation: University of Perugia, Perugia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rulli
authors.affiliation: University of Perugia, Perugia, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sidoni
authors.affiliation: Humanitas, Pisa, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Tinterri
authors.affiliation: USL, Prato, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Truglia
authors.affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000601:surgery*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007432:Intraoperative Period; D053539:Keratin-19 / Q000235:genetics*; D008197:Lymph Node Excision / Q000379:methods*; D008207:Lymphatic Metastasis; D008962:Models, Theoretical; D060787:Neoplasm Grading; D061206:Neoplasm Micrometastasis; D049451:Nomograms; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D053539:Keratin-19
keywords: CK19 mRNA number copies; Nomogram; Non Sentinel Node status; OSNA method