{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:02:12Z","timestamp":1774436532168,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Netzwerk Neuroendokrine Tumoren (NeT) e.V., Nuremberg, Germany"},{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare entity occurring in less than 4% of all lung cancers. Due to its low differentiation and high glucose transporter 1 (GLUT1) expression, LCNEC demonstrates an increased glucose turnover. Thus, PET\/CT with 2-[\n                      <jats:sup>18<\/jats:sup>\n                      F]-fluoro-deoxyglucose ([\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG) is suitable for LCNEC staging. Surgery with curative intent is the treatment of choice in early stage LCNEC. Prerequisite for this is correct lymph node staging. This study aimed at evaluating the diagnostic performance of [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT validated by histopathology following surgical resection or mediastinoscopy. N-staging interrater-reliability was assessed to test for robustness of the [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Between 03\/2014 and 12\/2020, 46 patients with LCNEC were included in this single center retrospective analysis. All underwent [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT for pre-operative staging and subsequently either surgery (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200938) or mediastinoscopy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098). Regarding the lymph node involvement, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT using the final histopathological N-staging (pN0 to pN3) as reference.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Per patient 14\u2009\u00b1\u20097 (range 4\u201332) lymph nodes were resected and histologically processed. 31\/46 patients had no LCNEC spread into the lymph nodes. In 8\/46 patients, the final stage was pN1, in 5\/46 pN2 and in 2\/46 pN3. [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT diagnosed lymph node metastasis of LCNEC with a sensitivity of 93%, a specificity of 87%, an accuracy of 89%, a PPV of 78% and a NPV of 96%. In the four false positive cases, the [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG uptake of the lymph nodes was 33 to 67% less in comparison with that of the respective LCNEC primary. Interrater-reliability was high with a strong level of agreement (\u03ba\u2009=\u20090.82).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In LCNEC N-staging with [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT demonstrates both high sensitivity and specificity, an excellent NPV but a slightly reduced PPV. Accordingly, preoperative invasive mediastinal staging may be omitted in cases with cN0 disease by [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT. In [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET\/CT cN1-cN3 stages histological confirmation is warranted, particularly in case of only moderate [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG uptake as compared to the LCNEC primary.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13550-021-00811-9","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T08:03:43Z","timestamp":1626941023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["N-staging in large cell neuroendocrine carcinoma of the lung: diagnostic value of [18F]FDG PET\/CT compared to the histopathology reference standard"],"prefix":"10.1186","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-5264","authenticated-orcid":false,"given":"Hubertus","family":"Hautzel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazan","family":"Alnajdawi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang P.","family":"Fendler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Rischpler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaid","family":"Darwiche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilfried E.","family":"Eberhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lale","family":"Umutlu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Theegarten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Stuschke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Schuler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"Aigner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Till","family":"Pl\u00f6nes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"811_CR1","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.1002\/cam4.2188","volume":"8","author":"J Gu","year":"2019","unstructured":"Gu J, Gong D, Wang Y, Chi B, Zhang J, Hu S, et al. The demographic and treatment options for patients with large cell neuroendocrine carcinoma of the lung. Cancer Med. 2019;8:2979\u201393.","journal-title":"Cancer Med"},{"key":"811_CR2","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s11748-014-0379-9","volume":"62","author":"A Iyoda","year":"2014","unstructured":"Iyoda A, Makino T, Koezuka S, Otsuka H, Hata Y. Treatment options for patients with large cell neuroendocrine carcinoma of the lung. Gen Thorac Cardiovasc Surg. 2014;62:351\u20136.","journal-title":"Gen Thorac Cardiovasc Surg"},{"key":"811_CR3","doi-asserted-by":"publisher","first-page":"7047","DOI":"10.1007\/s13277-016-5003-4","volume":"37","author":"G Lo Russo","year":"2016","unstructured":"Lo Russo G, Pusceddu S, Proto C, Macerelli M, Signorelli D, Vitali M, et al. Treatment of lung large cell neuroendocrine carcinoma. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2016;37:7047\u201357.","journal-title":"Tumour Biol J Int Soc Oncodevelopmental Biol Med"},{"key":"811_CR4","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1016\/j.jtho.2019.09.005","volume":"14","author":"V Raman","year":"2019","unstructured":"Raman V, Jawitz OK, Yang C-FJ, Voigt SL, Tong BC, D\u2019Amico TA, et al. Outcomes for surgery in large cell lung neuroendocrine cancer. J Thorac Oncol. 2019;14:2143\u201351.","journal-title":"J Thorac Oncol"},{"key":"811_CR5","first-page":"4219","volume":"33","author":"K Kaira","year":"2013","unstructured":"Kaira K, Murakami H, Endo M, Ohde Y, Naito T, Kondo H, et al. Biological correlation of 18F-FDG uptake on PET in pulmonary neuroendocrine tumors. Anticancer Res. 2013;33:4219\u201328.","journal-title":"Anticancer Res"},{"key":"811_CR6","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.2214\/AJR.06.0503","volume":"188","author":"S Chong","year":"2007","unstructured":"Chong S, Lee KS, Kim B-T, Choi JY, Yi CA, Chung MJ, et al. Integrated PET\/CT of pulmonary neuroendocrine tumors: diagnostic and prognostic implications. AJR Am J Roentgenol. 2007;188:1223\u201331.","journal-title":"AJR Am J Roentgenol"},{"key":"811_CR7","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.lungcan.2007.11.012","volume":"61","author":"YS Song","year":"2008","unstructured":"Song YS, Lee WW, Chung JH, Park SY, Kim YK, Kim SE. Correlation between FDG uptake and glucose transporter type 1 expression in neuroendocrine tumors of the lung. Lung Cancer. 2008;61:54\u201360.","journal-title":"Lung Cancer"},{"key":"811_CR8","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1016\/j.ejrad.2015.07.033","volume":"84","author":"KW Lee","year":"2015","unstructured":"Lee KW, Lee Y, Oh SW, Jin KN, Goo JM. Large cell neuroendocrine carcinoma of the lung: CT and FDG PET findings. Eur J Radiol. 2015;84:2332\u20138.","journal-title":"Eur J Radiol"},{"key":"811_CR9","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.athoracsur.2014.10.015","volume":"99","author":"F Eichhorn","year":"2015","unstructured":"Eichhorn F, Dienemann H, Muley T, Warth A, Hoffmann H. Predictors of survival after operation among patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg. 2015;99:983\u20139.","journal-title":"Ann Thorac Surg"},{"key":"811_CR10","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jtho.2015.09.009","volume":"11","author":"P Goldstraw","year":"2016","unstructured":"Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WEE, et al. The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11:39\u201351.","journal-title":"J Thorac Oncol"},{"key":"811_CR11","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1378\/chest.08-0978","volume":"136","author":"FC Detterbeck","year":"2009","unstructured":"Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136:260\u201371.","journal-title":"Chest"},{"key":"811_CR12","doi-asserted-by":"publisher","first-page":"261","DOI":"10.2214\/ajr.144.2.261","volume":"144","author":"GM Glazer","year":"1985","unstructured":"Glazer GM, Gross BH, Quint LE, Francis IR, Bookstein FL, Orringer MB. Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping. AJR Am J Roentgenol. 1985;144:261\u20135.","journal-title":"AJR Am J Roentgenol"},{"key":"811_CR13","doi-asserted-by":"publisher","first-page":"276","DOI":"10.11613\/BM.2012.031","volume":"22","author":"ML McHugh","year":"2012","unstructured":"McHugh ML. Interrater reliability: the kappa statistic. Biochem Med. 2012;22:276\u201382.","journal-title":"Biochem Med"},{"key":"811_CR14","doi-asserted-by":"publisher","first-page":"8369","DOI":"10.1007\/s13277-014-2102-y","volume":"35","author":"F Lococo","year":"2014","unstructured":"Lococo F, Cesario A, Paci M, Filice A, Versari A, Rapicetta C, et al. PET\/CT assessment of neuroendocrine tumors of the lung with special emphasis on bronchial carcinoids. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:8369\u201377.","journal-title":"Tumour Biol J Int Soc Oncodevelopmental Biol Med."},{"key":"811_CR15","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.lungcan.2019.03.013","volume":"132","author":"V Gr\u00f8ndahl","year":"2019","unstructured":"Gr\u00f8ndahl V, Binderup T, Langer SW, Petersen RH, Nielsen K, Kjaer A, et al. Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence. Lung Cancer. 2019;132:141\u20139.","journal-title":"Lung Cancer"},{"key":"811_CR16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.lungcan.2009.10.015","volume":"69","author":"C Casali","year":"2010","unstructured":"Casali C, Cucca M, Rossi G, Barbieri F, Iacuzio L, Bagni B, et al. The variation of prognostic significance of Maximum Standardized Uptake Value of [18F]-fluoro-2-deoxy-glucose positron emission tomography in different histological subtypes and pathological stages of surgically resected Non-Small Cell Lung Carcinoma. Lung Cancer. 2010;69:187\u201393.","journal-title":"Lung Cancer"},{"key":"811_CR17","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1007\/s00259-009-1291-x","volume":"37","author":"M Agarwal","year":"2010","unstructured":"Agarwal M, Brahmanday G, Bajaj SK, Ravikrishnan KP, Wong CYO. Revisiting the prognostic value of preoperative (18)F-fluoro-2-deoxyglucose ( (18)F-FDG) positron emission tomography (PET) in early-stage (I & II) non-small cell lung cancers (NSCLC). Eur J Nucl Med Mol Imaging. 2010;37:691\u20138.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"811_CR18","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1093\/ejcts\/ezu214","volume":"47","author":"T Yamamoto","year":"2015","unstructured":"Yamamoto T, Sakairi Y, Nakajima T, Suzuki H, Tagawa T, Iwata T, et al. Comparison between endobronchial ultrasound-guided transbronchial needle aspiration and 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of postoperative nodal recurrence in patients with lung cancer. Eur J Cardio-Thoracic Surg. 2015;47:234\u20138.","journal-title":"Eur J Cardio-Thoracic Surg"},{"issue":"45","key":"811_CR19","first-page":"185","volume":"2011","author":"SY Kwon","year":"2010","unstructured":"Kwon SY, Min J-J, Song H-C, Choi C, Na K-J, Bom H-S. Impact of lymphoid follicles and histiocytes on the False-Positive FDG uptake of lymph nodes in non-small cell lung cancer. Nucl Med Mol Imaging. 2010;2011(45):185\u201391.","journal-title":"Nucl Med Mol Imaging"},{"key":"811_CR20","first-page":"348","volume":"38","author":"GK Gedik","year":"2019","unstructured":"Gedik GK, Yilmaz F. Is there any improvement in clinical staging with (18)F-FDG PET\/CT compared to surgical staging in cases of lung cancer? Rev Esp Med Nucl Imagen Mol. 2019;38:348\u201354.","journal-title":"Rev Esp Med Nucl Imagen Mol"},{"key":"811_CR21","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.rx.2016.12.001","volume":"59","author":"ABG de Castro","year":"2017","unstructured":"de Castro ABG, Ferreir\u00f3s Dom\u00ednguez J, Delgado Bolton R, Fern\u00e1ndez P\u00e9rez C, Cabeza Mart\u00ednez B, Garc\u00eda-Garc\u00eda-Esquinas M, et al. PET-CT in presurgical lymph node staging in non-small cell lung cancer: the importance of false-negative and false-positive findings. Radiologia. 2017;59:147\u201358.","journal-title":"Radiologia"},{"key":"811_CR22","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1007\/s11748-020-01345-y","volume":"68","author":"GE Darling","year":"2020","unstructured":"Darling GE. Lymph node assessment in early stage non-small cell lung cancer lymph node dissection or sampling? Gen Thorac Cardiovasc Surg. 2020;68:716\u201324.","journal-title":"Gen Thorac Cardiovasc Surg"},{"issue":"48","key":"811_CR23","first-page":"41","volume":"2014","author":"AY Lee","year":"2010","unstructured":"Lee AY, Choi SJ, Jung KP, Park JS, Lee SM, Bae SK. Characteristics of metastatic mediastinal lymph nodes of non-small cell lung cancer on preoperative F-18 FDG PET\/CT. Nucl Med Mol Imaging. 2010;2014(48):41\u20136.","journal-title":"Nucl Med Mol Imaging"},{"key":"811_CR24","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3892\/mco.2014.408","volume":"3","author":"J Xue","year":"2015","unstructured":"Xue J, Zheng J, Guo H, Wang X, Han A. Predictive value of 18(F)-fluorodeoxyglucose positron emission tomography\u2014computed tomography compared to postoperative pathological findings for patients with non-small-cell lung cancer. Mol Clin Oncol. 2015;3:109\u201314.","journal-title":"Mol Clin Oncol"},{"key":"811_CR25","doi-asserted-by":"publisher","first-page":"281","DOI":"10.4103\/1450-1147.215486","volume":"16","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Elam Y, Hall P, Williams H, Pucar D, Patel V. The role of fluorodeoxy-D-glucose positron emission tomography\/computed tomography in nodal staging of nonsmall cell lung cancer in sequential surgical algorithm. World J Nucl Med. 2017;16:281\u20135.","journal-title":"World J Nucl Med"},{"key":"811_CR26","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cpet.2017.09.006","volume":"13","author":"G Cheng","year":"2018","unstructured":"Cheng G. Non-small-cell lung cancer PET imaging beyond F18 fluorodeoxyglucose. PET Clin. 2018;13:73\u201381.","journal-title":"PET Clin"},{"key":"811_CR27","doi-asserted-by":"publisher","first-page":"9288","DOI":"10.18632\/oncotarget.7063","volume":"7","author":"C Lapa","year":"2016","unstructured":"Lapa C, L\u00fcckerath K, Rudelius M, Schmid J-S, Schoene A, Schirbel A, et al. [68Ga]Pentixafor-PET\/CT for imaging of chemokine receptor 4 expression in small cell lung cancer\u2013initial experience. Oncotarget. 2016;7:9288\u201395.","journal-title":"Oncotarget"},{"key":"811_CR28","doi-asserted-by":"publisher","first-page":"801","DOI":"10.2967\/jnumed.119.227967","volume":"60","author":"C Kratochwil","year":"2019","unstructured":"Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. (68)Ga-FAPI PET\/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801\u20135.","journal-title":"J Nucl Med"}],"container-title":["EJNMMI Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13550-021-00811-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13550-021-00811-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13550-021-00811-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T08:10:05Z","timestamp":1626941405000},"score":1,"resource":{"primary":{"URL":"https:\/\/ejnmmires.springeropen.com\/articles\/10.1186\/s13550-021-00811-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["811"],"URL":"https:\/\/doi.org\/10.1186\/s13550-021-00811-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-513428\/v1","asserted-by":"object"}]},"ISSN":["2191-219X"],"issn-type":[{"value":"2191-219X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]},"assertion":[{"value":"10 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 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":"This was a retrospective analysis of available patient data which was performed according to the Declaration of Helsinki and approved by the local ethics committee (Ethics committee, University Duisburg-Essen, faculty of medicine). Informed consent was obtained from all participating subjects.","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":"Hubertus Hautzel, Yazan Alnajdawi, Christoph Rischpler, Kaid Darwiche, Wilfried E. Eberhardt, Dirk Theegarten, Martin Stuschke, Clemens Aigner and Till Pl\u00f6nes have nothing to disclose. Wolfgang P. Fendler reports personal fees and other from Endocyte, personal fees and other from BTG, personal fees from RadioMedix, personal fees from Bayer Healthcare, personal fees from Parexel, outside the submitted work. Lale Umutlu reports grants, personal fees and other from Siemens Healthineers and personal fees and other from Bayer Healthcare outside the submitted work. Martin Schuler received research funding from AstraZeneca, Boehringer Ingelheim, and Bristol Myers-Squibb and reports personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, MorphoSys, Novartis, Roche, Takeda, Amgen, MSD\u00a0outside the submitted work. Ken Herrmann reports personal fees from Siemens Healthineers, personal fees from Bayer Healthcare, 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 GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, outside the submitted work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"68"}}