Adam R Belanger1, Johnathan Hollyfield2, Gabriella Yacovone3, Agathe S Ceppe4, Jason A Akulian1, A Cole Burks1, M Patricia Rivera1, Leslie G Dodd2, Jason M Long5, Benjamin E Haithcock5, Chad V Pecot3. 1. Section of Interventional Pulmonology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. 2. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA. 3. Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. 4. Marsico Lung Institute/Cystic Fibrosis Research Center, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. 5. Division of Cardiothoracic Surgery, Department of Surgery, University of North Carolina, Chapel Hill, NC, USA.
Abstract
BACKGROUND: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. METHODS: We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. RESULTS: Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs. 1,293 days, P=0.0093) and overall survival (median 239 vs. 1,120 days, P=0.0357). CONCLUSIONS: Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm.
BACKGROUND: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. METHODS: We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. RESULTS: Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs. 1,293 days, P=0.0093) and overall survival (median 239 vs. 1,120 days, P=0.0357). CONCLUSIONS: Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm.
Authors: Robert Timmerman; Rebecca Paulus; James Galvin; Jeffrey Michalski; William Straube; Jeffrey Bradley; Achilles Fakiris; Andrea Bezjak; Gregory Videtic; David Johnstone; Jack Fowler; Elizabeth Gore; Hak Choy Journal: JAMA Date: 2010-03-17 Impact factor: 56.272
Authors: Beatrix Cucuruz; Sebastian Dango; Vindi Jurinovic; Olga Mayer; Marie Follo; Joachim Böhm; Nikolaus Freudenberg; Mirjam Elze; Wulf Sienel; Christoph A Klein; Bernward Passlick; Bernhard Polzer Journal: J Thorac Oncol Date: 2012-04 Impact factor: 15.609
Authors: Michael B Wallace; Mark I Block; William Gillanders; James Ravenel; Brenda J Hoffman; Carolyn E Reed; Mostafa Fraig; David Cole; Michael Mitas Journal: Chest Date: 2005-02 Impact factor: 9.410
Authors: Valerie W Rusch; Debra Hawes; Paul A Decker; Sue Ellen Martin; Andrea Abati; Rodney J Landreneau; G Alexander Patterson; Richard I Inculet; David R Jones; Richard A Malthaner; Robbin G Cohen; Karla Ballman; Joe B Putnam; Richard J Cote Journal: J Clin Oncol Date: 2011-10-11 Impact factor: 44.544
Authors: S Dango; B Cucuruz; O Mayer; S Brabletz; M Follo; M Elze; W Sienel; T Brabletz; B Passlick Journal: Lung Cancer Date: 2009-09-04 Impact factor: 5.705
Authors: Laila Khazai; Uma R Kundu; Betsy Jacob; Shobha Patel; Nour Sneige; George A Eapen; Rodolfo C Morice; Nancy P Caraway Journal: Cytojournal Date: 2011-05-31 Impact factor: 2.091
Authors: Maja Guberina; Kaid Darwiche; Hubertus Hautzel; Christoph Pöttgen; Nika Guberina; Thomas Gauler; Till Ploenes; Lale Umutlu; Dirk Theegarten; Clemens Aigner; Wilfried E E Eberhardt; Martin Metzenmacher; Marcel Wiesweg; Rüdiger Karpf-Wissel; Martin Schuler; Ken Herrmann; Martin Stuschke Journal: Radiat Oncol Date: 2021-09-15 Impact factor: 3.481