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

BackgroundTumor-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).MethodsThe 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.ResultsThe 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%).ConclusionsThe 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.

Application of OSNA Nomogram in Patients With Macrometastatic Sentinel Lymph Node: A Retrospective Assessment of Accuracy

“…Former research, through which the OSNA nomogram was validated, 4 considered a population of patients for whom complete ALND was performed even if micrometastasis were found in the SLN. Our study, instead, could not assess the accuracy of OSNA nomogram for the population of patients with micrometastasis in the SLN, because the histologic data on NSLN was missing.…”

“…Complete ALND could be avoided in patients with nomogram lower than 31% while, when the nomogram is higher than 31%, it should still be recommended. 4,5 Our study population included 141 patients who underwent surgery in the service of Breast Surgical Oncology of Modena University Hospital (Italy) in the period from April 2015 to March 2018. The patients enrolled in the study fulfilled the following criteria, which are also resumed in Table 1: • Diagnosis of invasive carcinoma of the breast in stage T1-T3 with indication to surgery as primary therapeutic procedure.…”

“…On these grounds, "European OSNA Committee" (a group of 22 European centers where OSNA technique is routinely used), developed a nomogram aimed to predict NSLN status, thus helping to offer the best treatment for each patient. 4 OSNA nomogram was designed and validated through a clinical trial involving around 4000 patients having their SLN processed with OSNA. 4,5 It appears that predictive models that have a good performance in one population, may not have the same results when applied to other population.…”

“…4 OSNA nomogram was designed and validated through a clinical trial involving around 4000 patients having their SLN processed with OSNA. 4,5 It appears that predictive models that have a good performance in one population, may not have the same results when applied to other population. The aim of the study was to verify diagnostic accuracy of OSNA nomogram through its retrospective application in a group of patients who already underwent sentinel node biopsy and subsequent…”

Detection of CK19 mRNA Using One-step Nucleic Acid Amplification (OSNA) in Prostate Cancer: Preliminary Results

“…During the last few years, new biomolecular techniques have been used to assess LN metastases. In breast cancer, one-step nucleic acid amplification (OSNA) has recently been indicated as a fast-molecular intraoperative approach for the detection of LN metastases 19, 20, 21. This procedure exploits that CK19 is normally not expressed in lymphatic tissue.…”