Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

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Abstract

Background

There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC.

Methods

Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described.

Results

Suggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team.

Conclusions

To optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential.

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Most cited references 36

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Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer.

Paul De Leyn, Christophe Dooms, Jaroslaw Kuzdzal … (2014)

Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with potentially resectable non-small-cell lung cancer (NSCLC) is of paramount importance. In 2007, the European Society of Thoracic Surgeons (ESTS) published an algorithm on preoperative mediastinal staging integrating imaging, endoscopic and surgical techniques. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a new lymph node map. Some changes in this map have an important impact on mediastinal staging. Moreover, more evidence of the different mediastinal staging technique has become available. Therefore, a revision of the ESTS guidelines was needed. In case of computed tomography (CT)-enlarged or positron emission tomography (PET)-positive mediastinal lymph nodes, tissue confirmation is indicated. Endosonography [endobronchial ultrasonography (EBUS)/esophageal ultrasonography (EUS)] with fine-needle aspiration (FNA) is the first choice (when available), since it is minimally invasive and has a high sensitivity to rule in mediastinal nodal disease. If negative, surgical staging with nodal dissection or biopsy is indicated. Video-assisted mediastinoscopy is preferred to mediastinoscopy. The combined use of endoscopic staging and surgical staging results in the highest accuracy. When there are no enlarged lymph nodes on CT and when there is no uptake in lymph nodes on PET or PET-CT, direct surgical resection with systematic nodal dissection is indicated for tumours ≤ 3 cm located in the outer third of the lung. In central tumours or N1 nodes, preoperative mediastinal staging is indicated. The choice between endoscopic staging with EBUS/EUS and FNA or video-assisted mediastinoscopy depends on local expertise to adhere to minimal requirements for staging. For tumours >3 cm, preoperative mediastinal staging is advised, mainly in adenocarcinoma with high standardized uptake value. For restaging, invasive techniques providing histological information are advisable. Both endoscopic techniques and surgical procedures are available, but their negative predictive value is lower compared with the results obtained in baseline staging. An integrated strategy using endoscopic staging techniques to prove mediastinal nodal disease and mediastinoscopy to assess nodal response after induction therapy needs further study.

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Identifying and targeting ROS1 gene fusions in non-small cell lung cancer.

Kurtis Davies, Anh Le, Mariana Theodoro … (2012)

Oncogenic gene fusions involving the 3' region of ROS1 kinase have been identified in various human cancers. In this study, we sought to characterize ROS1 fusion genes in non-small cell lung cancer (NSCLC) and establish the fusion proteins as drug targets. An NSCLC tissue microarray (TMA) panel containing 447 samples was screened for ROS1 rearrangement by FISH. This assay was also used to screen patients with NSCLC. In positive samples, the identity of the fusion partner was determined through inverse PCR and reverse transcriptase PCR. In addition, the clinical efficacy of ROS1 inhibition was assessed by treating a ROS1-positive patient with crizotinib. The HCC78 cell line, which expresses the SLC34A2-ROS1 fusion, was treated with kinase inhibitors that have activity against ROS1. The effects of ROS1 inhibition on proliferation, cell-cycle progression, and cell signaling pathways were analyzed by MTS assay, flow cytometry, and Western blotting. In the TMA panel, 5 of 428 (1.2%) evaluable samples were found to be positive for ROS1 rearrangement. In addition, 1 of 48 patients tested positive for rearrangement, and this patient showed tumor shrinkage upon treatment with crizotinib. The patient and one TMA sample displayed expression of the recently identified SDC4-ROS1 fusion, whereas two TMA samples expressed the CD74-ROS1 fusion and two others expressed the SLC34A2-ROS1 fusion. In HCC78 cells, treatment with ROS1 inhibitors was antiproliferative and downregulated signaling pathways that are critical for growth and survival. ROS1 inhibition may be an effective treatment strategy for the subset of patients with NSCLC whose tumors express ROS1 fusion genes. ©2012 AACR.

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Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology.

Neal I. Lindeman, Sanja Dacic, Ellen Beasley … (2013)

To establish evidence-based recommendations for the molecular analysis of lung cancers that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed. Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies. Three unbiased literature searches of electronic databases were performed to capture articles published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation. Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4). The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines.

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Author and article information

Journal

Journal ID (nlm-ta): Thorax

Journal ID (iso-abbrev): Thorax

Journal ID (hwp): thoraxjnl

Journal ID (publisher-id): thorax

Title: Thorax

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Print): 0040-6376

ISSN (Electronic): 1468-3296

Publication date (Print): February 2016

Publication date (Electronic): 3 November 2015

Volume: 71

Issue: 2

Pages: 177-184

Affiliations

[1 ]Institute of Pathology, Charité Universitätsmedizin Berlin , Berlin, Germany

[2 ]Institute of Pathology, University Hospital Basel , Basel, Switzerland

[3 ]Department of Respiratory Diseases, Maastricht University Medical Center , Maastricht, The Netherlands

[4 ]Respiratory Division, University Hospitals KU Leuven , Leuven, Belgium

[5 ]Department of Laboratory Medicine, Pathology, Örebro University Hospital , Örebro, Sweden

[6 ]Department of Radiology, Hospital Universitario 12 de Octubre , Madrid, Spain

[7 ]Aberdeen University Medical School , Aberdeen, UK

[8 ]Academic Division of Thoracic Surgery, The Royal Brompton Hospital and Imperial College , London, UK

[9 ]Laboratorio de Dianas Terapéuticas, Hospital Universitario HM Sanchinarro , Madrid, Spain

[10 ]Department of Pathology, VU University Medical Center , Amsterdam, The Netherlands

[11 ]Department of Thoracic and Vascular Surgery, Antwerp University Hospital , Antwerp, Belgium

Author notes

[Correspondence to ] Professor Manfred Dietel, Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Charité, Charitéplatz 1, Berlin 10117, Germany; manfred.dietel@ 123456charite.de

Article

Publisher ID: thoraxjnl-2014-206677

DOI: 10.1136/thoraxjnl-2014-206677

PMC ID: 4752623

PubMed ID: 26530085

SO-VID: 97e1198b-70cd-499e-adfe-11d4e7006973

Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

History

Date received : 10 December 2014

Date revision received : 10 June 2015

Date accepted : 21 July 2015

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ScienceOpen disciplines: Surgery

Keywords: non-small cell lung cancer,histology/cytology

Data availability:

ScienceOpen disciplines: Surgery

Keywords: non-small cell lung cancer, histology/cytology

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Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

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Abstract

Background

Methods

Results

Conclusions

Related collections

Karger: Oncology

Most cited references 36

Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer.

Identifying and targeting ROS1 gene fusions in non-small cell lung cancer.

Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology.

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