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Inclusion criteria were curative treatment intent, <jats:sup>18<\/jats:sup>F-FDG PET\/CT and EBUS-TBNA prior to start of treatment. The lymphatic drainage was classified into echelon-1 (ipsilateral hilum), echelon-2 (ipsilateral LN-stations 4 and 7) and echelon-3 (rest of the mediastinum, contralateral hilum). The pattern of spread was classified according to all permutations of echelon-1, echelon-2, and echelon-3 EBUS-TBNA findings.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001, exact symmetry test). In a multivariable logistic model for EBUS-positivity at echelon-3, prognostic factors were PET-positivity at echelon-3 (Hazard ratio (HR)\u2009=\u200912.1; 95%-CI: 3.2\u201346.5), EBUS-TBNA positivity at echelon-2 (HR\u2009=\u20096.7; 95%-CI: 1.31\u201331.2) and left-sided tumor location (HR\u2009=\u20094.0; 95%-CI: 1.24\u201313.2). There were significantly less combined ipsilateral upper (LN-stations 2 and 4) and lower (LN-station 7) mediastinal involvements (16.8% of patients) with EBUS-TBNA than with PET (38.9%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001, exact symmetry test). EBUS-TBNA detected a lobe specific heterogeneity between the odds ratios of LN-positivity in the upper versus lower mediastinum (<jats:italic>p<\/jats:italic>\u2009=\u20090.0021, Breslow-Day test), while PET did not (<jats:italic>p<\/jats:italic>\u2009=\u20090.19).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Frequent patterns of LN-metastatic spread could be defined by EBUS-TBNA and PET and discrepancies in the pattern were seen between both methods. EBUS-TBNA showed more lobe and tumor laterality specific patterns of LN-metastases than PET and skipped lymph node stations were rare. These systematic relations offer the opportunity to further refine multi-parameter risk of LN-involvement models for target volume delineation based on pattern of spread by EBUS-TBNA and PET.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13014-021-01904-4","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T10:04:18Z","timestamp":1631700258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Patterns of nodal spread in stage III NSCLC: importance of EBUS-TBNA and 18F-FDG PET\/CT for radiotherapy target volume definition"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-0539","authenticated-orcid":false,"given":"Maja","family":"Guberina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaid","family":"Darwiche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubertus","family":"Hautzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"P\u00f6ttgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nika","family":"Guberina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gauler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Ploenes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lale","family":"Umutlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Theegarten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Aigner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried E. 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Lung Cancer. 2021;156:122\u20138.","journal-title":"Lung Cancer"}],"container-title":["Radiation Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-021-01904-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13014-021-01904-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-021-01904-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T11:06:48Z","timestamp":1631704008000},"score":1,"resource":{"primary":{"URL":"https:\/\/ro-journal.biomedcentral.com\/articles\/10.1186\/s13014-021-01904-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1904"],"URL":"https:\/\/doi.org\/10.1186\/s13014-021-01904-4","relation":{},"ISSN":["1748-717X"],"issn-type":[{"value":"1748-717X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,15]]},"assertion":[{"value":"10 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics committee of the medical faculty, University Duisburg-Essen, UK Essen 19-9056-BO.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Maja Guberina, Nika Guberina, Lale Umutlu, Till Ploenes, Hubertus Hautzel, Dirk Theegarten, Clemens Aigner; R\u00fcdiger Karpf-Wissel. There are no relationships\/conditions\/circumstances that present a potential conflict of interest. All authors declare that they have no conflict of interest. Christoph P\u00f6ttgen reports personal honoraria from Roche Pharma, personal fees from Boehringer Ingelheim, personal fees from Astra Zeneca, outside the submitted work. There are no relationships\/conditions\/circumstances that present a potential conflict of interest. Thomas Gauler: advisory board or consultant: Ipsen, No-vartis, BMS, Eisai; honoraria: BMS, Ipsen, Novartis, MSD, Eisai, Pfizer; traveling expenses: BMS, Ipsen, Novartis, MSD, Eisai, Pfiz-er; stocks: Bayer. Martin Metzenmacher reports honoraria from BMS, Boehringer Ingelheim, MSD, Roche, Takeda. Marcel Wiesweg: Honoraria: Amgen, Boehringer Ingelheim, Novartis, Roche, Takeda. Research Funding: Bristol-Myers Squibb, Takeda. Ken Herrmann reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Bain Capital, personal fees from MPM Capital, outside the submitted work. Kaid Darwiche received travel grants from Olympus and Boston Scientific. There are no relationships\/conditions\/circumstances that present a potential conflict of interest. W. E. E. Eberhardt: Honoraria (Advisory board function) Astra Zeneca, BMS, Roche, MSD, Pfizer, Boehringer, Takeda, Eli Lilly, Bayer, Celgene. Honoraria (educational lectures) BMS, MSD Astra Zeneca, Roche, Novartis, Pfizer, Boehringer, Takeda, Abbvie, Celgene, Eli Lilly. Research grant: Eli Lilly, BMS, Astra Zeneca; Other: none. The author declares that no competing interests exist. Martin Schuler: Consultant (compensated): AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Roche, Takeda. Stock ownership: none. Honoraries for CME presentations: Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, MSD, Novartis. Research funding to institution: AstraZeneca, Boehringer Ingelheim, Bristol Myers-Squibb, Novartis. MS confirms that the above mentioned funding source was not involved in the study design or materials used, neither in the collection, analysis, and interpretation of data nor in the writing of the paper. Martin Stuschke: Honoraria (Advisory board function) AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, Janssen-Cilag Research funding to institution by AstraZeneca in 2019 and 2020. Prof. Dr. Martin Stuschke confirms that the above mentioned funding source was not involved in the study design or materials used, neither in the collection, analysis, and interpretation of data nor in the writing of the paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"176"}}