Evaluation of Lymph Node Analysis Using One Step Nucleic Acid Amplification (OSNA) in Patients With Lung Cancer Who Underwent Robotic Lung Resection, Comparison With Traditional Methods

Overview

This prospective study aims to evaluate the effectiveness of the One-Step Nucleic Acid Amplification (OSNA) technique for detecting micrometastases in lymph nodes of patients with clinical stage I-II non-small cell lung cancer (NSCLC) undergoing robotic lung resection. OSNA targets CK19 mRNA expression in order to improve the accuracy of mediastinal lymph node staging. The secondary objectives are to identify skip metastases, evaluate the potential for pathological upstaging and analyse long-term outcomes such as overall survival (OS) and disease-free survival (DFS). This prospective study was approved by the local Ethics Committee in December 2022, and patient enrolment began in May 2023. The inclusion criteria were: * Resectable non-small cell lung cancer (NSCLC). * Clinical stage I-II. * Absence of pathological lymphadenopathy in preoperative staging (cN0). The exclusion criteria included: * Clinically advanced NSCLC * Neoadjuvant chemo-immunotherapy * Presence of other oncological diseases * Patient refusal to participate. All patients underwent robotic anatomical lung resection combined with systematic lymphadenectomy. Patients were randomised into two groups based on the lymph node (LN) analysis method: OSNA technique or standard histopathological analysis (hematoxylin and eosin or immunohistochemistry).

Detailed description

This prospective study aims to evaluate the effectiveness of the One-Step Nucleic Acid Amplification (OSNA) technique for detecting micrometastases in lymph nodes of patients with clinical stage I-II non-small cell lung cancer (NSCLC) undergoing robotic lung resection. OSNA targets CK19 mRNA expression in order to improve the accuracy of mediastinal lymph node staging.

Cytokeratin 19 is a cytoskeletal component exclusively found in normal or neoplastic epithelial cells, and its presence in lymph nodes serves as an indicator of involvement by tumor cells of epithelial origin.The OSNA method represents a novel approach that determines the number of mRNA copies in the homogenized entire lymph node, overcoming the limitations of hematoxylin- eosin and immunohistochemistry methods that only analyze histological sections and avoiding sampling bias due to the non-uniform localization of metastatic foci. The present study aims to evaluate the advantages of using molecular lymph node assessment in homogeneous samples of patients with the same clinical stage of tumour presentation, stage I and II N0 NSCLC, to optimise data comparison and reduce the risk of potential bias.

Secondary objectives will be the identification of skip metastases and lymph node upstaging.

The future perspective of the study is to analyse long-term follow-up data through outpatient surveillance and radiological examinations to estimate possible disease recurrence and mortality rates in patients The secondary objectives are to identify skip metastases, evaluate the potential for pathological upstaging and analyse long-term outcomes such as overall survival (OS) and disease-free survival (DFS).

Interventions

• Diagnostic test lymph node analysis using the OSNA assay
  lymph node analysis using the OSNA assay in early stage NSCLC patients

Primary outcome measures

• Number of Participants with nodal micrometastasis with OSNA analisis [Time frame: through study completion, an average of 5 year]

Eligibility criteria

Inclusion criteria

• Resectable non-small cell lung cancer (NSCLC)
• Clinical stage I-II
• Absence of pathological lymphadenopathy in preoperative staging (cN0)

Exclusion criteria

• Clinically advanced NSCLC
• Prior neoadjuvant chemo-immunotherapy
• Presence of other oncological diseases
• Patient refusal to participate.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

Italy · 1 center

• University of Pisa — Pisa

Publications

• Romano G, Zirafa CC, Calabro F, Ali G, Manca G, De Liperi A, Proietti A, Manfredini B, Di Stefano I, Marciano A, Davini F, Volterrani D, Melfi F. Sentinel Lymph Node Mapping in Lung Cancer: A Pilot Study for the Detection of Micrometastases in Stage I Non-Small Cell Lung Cancer. Tomography. 2024 May 15;10(5):761-772. doi: 10.3390/tomography10050058. PMID 38787018
• Nakagawa K, Asamura H, Tsuta K, Nagai K, Yamada E, Ishii G, Mitsudomi T, Ito A, Higashiyama M, Tomita Y, Inoue M, Morii E, Matsuura N, Okumura M. The novel one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node metastasis in patients with non-small cell lung cancer (NSCLC): Results of a multicenter prospective study. Lung Cancer. 2016 Jul;97:1-7. doi: 10.1016/j.lungcan.20 PMID 27237020
• Masai K, Nakagawa K, Yoshida A, Sakurai H, Watanabe S, Asamura H, Tsuta K. Cytokeratin 19 expression in primary thoracic tumors and lymph node metastases. Lung Cancer. 2014 Dec;86(3):318-23. doi: 10.1016/j.lungcan.2014.09.018. Epub 2014 Oct 12. PMID 25453845
• Vodicka J, Mukensnabl P, Vejvodova S, Spidlen V, Kulda V, Topolcan O, Pesta M. A more sensitive detection of micrometastases of NSCLC in lymph nodes using the one-step nucleic acid amplification (OSNA) method. J Surg Oncol. 2018 Feb;117(2):163-170. doi: 10.1002/jso.24826. Epub 2017 Dec 4. PMID 29205350

Identifiers

NCT: NCT07301983 · 22283

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗