{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:09:09Z","timestamp":1780546149891,"version":"3.54.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T00:00:00Z","timestamp":1577491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T00:00:00Z","timestamp":1577491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005788","name":"Medizinische Universit\u00e4t Wien","doi-asserted-by":"publisher","award":["n.a."],"award-info":[{"award-number":["n.a."]}],"id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["HORM CANC"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As endocrinological parameters such as thyroid hormones modulate proliferative, metabolic, and angiogenic pathways, it is surmised that their levels can be associated with cancer development and progression. Most patients with gastroesophageal cancer are diagnosed very late and have a poor prognosis, yet the association with endocrinological parameters has not been addressed so far. The aim of this study was to correlate hormones with the outcome, so new prognostic and potentially therapeutic markers can be defined. We analyzed clinical and endocrinological parameters including history of thyroid disorders and laboratory analyses of thyroid hormones and correlated these with the overall survival in a large European cohort of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. In total, the survival outcome of 258 patients was evaluated. Higher levels of fT4 (<jats:italic>p<\/jats:italic>\u2009=\u20090.041, HR\u2009=\u20092.202) and lower levels of T3 (<jats:italic>p<\/jats:italic>\u00a0=\u20090,003, HR\u2009=\u20090,141) were associated with significantly shorter survival. However, the overall survival of patients with known thyroid disorders did not differ significantly from euthyroid patients (euthyroid, 283\u00a0days; hyperthyroid, 354\u00a0days; hypothyroid, 284\u00a0days; <jats:italic>p<\/jats:italic>\u2009=\u20090.472). Elevated fT4 levels are associated with poorer overall survival of patients with gastroesophageal cancer in advanced stages. Since data on the correlation of endocrinological parameters and gastroesophageal cancer are scarce, this analysis is an important impulse for further studies concerning the impact of thyroxine on patients with cancer of the upper GI tract.<\/jats:p>","DOI":"10.1007\/s12672-019-00374-1","type":"journal-article","created":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T11:02:41Z","timestamp":1577530961000},"page":"42-51","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Elevated Free Thyroxine Levels Are Associated with Poorer Overall Survival in Patients with Gastroesophageal Cancer: A Retrospective Single Center Analysis"],"prefix":"10.1007","volume":"11","author":[{"given":"H. C.","family":"Puhr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. S.","family":"Berghoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. F.","family":"Schoppmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Preusser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-0873","authenticated-orcid":false,"given":"Aysegul","family":"Ilhan-Mutlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,28]]},"reference":[{"issue":"5","key":"374_CR1","doi-asserted-by":"publisher","first-page":"E359","DOI":"10.1002\/ijc.29210","volume":"136","author":"J Ferlay","year":"2015","unstructured":"Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359\u2013E386. https:\/\/doi.org\/10.1002\/ijc.29210","journal-title":"Int J Cancer"},{"issue":"suppl 5","key":"374_CR2","doi-asserted-by":"publisher","first-page":"v50","DOI":"10.1093\/annonc\/mdw329","volume":"27","author":"F Lordick","year":"2016","unstructured":"Lordick F, Mariette C, Haustermans K, Obermannova R, Arnold D (2016) Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 27(suppl 5):v50\u2013v57. https:\/\/doi.org\/10.1093\/annonc\/mdw329","journal-title":"Ann Oncol"},{"issue":"suppl 5","key":"374_CR3","doi-asserted-by":"publisher","first-page":"v38","DOI":"10.1093\/annonc\/mdw350","volume":"27","author":"EC Smyth","year":"2016","unstructured":"Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D (2016) Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 27(suppl 5):v38\u2013v49. https:\/\/doi.org\/10.1093\/annonc\/mdw350","journal-title":"Ann Oncol"},{"key":"374_CR4","unstructured":"National Cancer Institute Bethesda MD SEER Cancer Stat Facts: Esophageal Cancer. https:\/\/seer.cancer.gov\/statfacts\/html\/esoph.html Accessed 10 October, 2019"},{"key":"374_CR5","unstructured":"National Cancer Institute Bethesda MD SEER Cancer Stat Facts: Stomach Cancer. https:\/\/seer.cancer.gov\/statfacts\/html\/stomach.html Accessed 10 October, 2019"},{"issue":"3","key":"374_CR6","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s10456-014-9418-5","volume":"17","author":"SA Mousa","year":"2014","unstructured":"Mousa SA, Lin HY, Tang HY, Hercbergs A, Luidens MK, Davis PJ (2014) Modulation of angiogenesis by thyroid hormone and hormone analogues: implications for cancer management. Angiogenesis 17(3):463\u2013469. https:\/\/doi.org\/10.1007\/s10456-014-9418-5","journal-title":"Angiogenesis"},{"issue":"9","key":"374_CR7","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.1172\/jci60047","volume":"122","author":"GA Brent","year":"2012","unstructured":"Brent GA (2012) Mechanisms of thyroid hormone action. J Clin Invest 122(9):3035\u20133043. https:\/\/doi.org\/10.1172\/jci60047","journal-title":"J Clin Invest"},{"issue":"15","key":"374_CR8","doi-asserted-by":"publisher","first-page":"6312","DOI":"10.18632\/oncotarget.2205","volume":"5","author":"K Cohen","year":"2014","unstructured":"Cohen K, Flint N, Shalev S, Erez D, Baharal T, Davis PJ, Hercbergs A, Ellis M, Ashur-Fabian O (2014) Thyroid hormone regulates adhesion, migration and matrix metalloproteinase 9 activity via alphavbeta3 integrin in myeloma cells. Oncotarget 5(15):6312\u20136322. https:\/\/doi.org\/10.18632\/oncotarget.2205","journal-title":"Oncotarget"},{"issue":"5","key":"374_CR9","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1097\/MED.0b013e32833d9710","volume":"17","author":"AH Hercbergs","year":"2010","unstructured":"Hercbergs AH, Ashur-Fabian O, Garfield D (2010) Thyroid hormones and cancer: clinical studies of hypothyroidism in oncology. Curr Opin endocrinol Diabetes Obes 17(5):432\u2013436. https:\/\/doi.org\/10.1097\/MED.0b013e32833d9710","journal-title":"Curr Opin endocrinol Diabetes Obes"},{"issue":"7","key":"374_CR10","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1016\/j.bbagen.2012.04.002","volume":"1830","author":"WG Kim","year":"2013","unstructured":"Kim WG, Cheng SY (2013) Thyroid hormone receptors and cancer. Biochim Biophys Acta 1830(7):3928\u20133936. https:\/\/doi.org\/10.1016\/j.bbagen.2012.04.002","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"374_CR11","doi-asserted-by":"publisher","first-page":"R19","DOI":"10.1530\/ERC-12-0219","volume":"20","author":"LC Moeller","year":"2013","unstructured":"Moeller LC, Fuhrer D (2013) Thyroid hormone, thyroid hormone receptors, and cancer: a clinical perspective. Endocr Relat Cancer 20(2):R19\u2013R29. https:\/\/doi.org\/10.1530\/ERC-12-0219","journal-title":"Endocr Relat Cancer"},{"issue":"2","key":"374_CR12","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer (Oxford, England : 1990) 45(2):228\u2013247. https:\/\/doi.org\/10.1016\/j.ejca.2008.10.026","journal-title":"Eur J Cancer (Oxford, England : 1990)"},{"issue":"2","key":"374_CR13","first-page":"245","volume":"10","author":"A Hercbergs","year":"1996","unstructured":"Hercbergs A (1996) The thyroid gland as an intrinsic biologic response-modifier in advanced neoplasia \u2013 a novel paradigm. In vivo (Athens, Greece) 10(2):245\u2013247","journal-title":"In vivo (Athens, Greece)"},{"issue":"13","key":"374_CR14","doi-asserted-by":"publisher","first-page":"11038","DOI":"10.18632\/oncotarget.3566","volume":"6","author":"ID Fabian","year":"2015","unstructured":"Fabian ID, Rosner M, Fabian I, Vishnevskia-Dai V, Zloto O, Shinderman Maman E, Cohen K, Ellis M, Lin HY, Hercbergs A, Davis PJ, Ashur-Fabian O (2015) Low thyroid hormone levels improve survival in murine model for ocular melanoma. Oncotarget 6(13):11038\u201311046. https:\/\/doi.org\/10.18632\/oncotarget.3566","journal-title":"Oncotarget"},{"issue":"12","key":"374_CR15","doi-asserted-by":"publisher","first-page":"5030","DOI":"10.1210\/jc.2016-2104","volume":"101","author":"SR Khan","year":"2016","unstructured":"Khan SR, Chaker L, Ruiter R, Aerts JG, Hofman A, Dehghan A, Franco OH, Stricker BH, Peeters RP (2016) Thyroid function and cancer risk: the Rotterdam study. J Clin Endocrinol Metab 101(12):5030\u20135036. https:\/\/doi.org\/10.1210\/jc.2016-2104","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"374_CR16","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1002\/(SICI)1097-0142(19991015)86:8<1596::AID-CNCR30>3.0.CO;2-C","volume":"86","author":"C Theodossiou","year":"1999","unstructured":"Theodossiou C, Skrepnik N, Robert EG, Prasad C, Axelrad TW, Schapira DV, Hunt JD (1999) Propylthiouracil-induced hypothyroidism reduces xenograft tumor growth in athymic nude mice. Cancer 86(8):1596\u20131601","journal-title":"Cancer"},{"issue":"2","key":"374_CR17","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1158\/1055-9965.EPI-08-0911","volume":"18","author":"AI Hellevik","year":"2009","unstructured":"Hellevik AI, Asvold BO, Bjoro T, Romundstad PR, Nilsen TI, Vatten LJ (2009) Thyroid function and cancer risk: a prospective population study. Cancer Epidemiol Biomark Prev 18(2):570\u2013574. https:\/\/doi.org\/10.1158\/1055-9965.EPI-08-0911","journal-title":"Cancer Epidemiol Biomark Prev"},{"issue":"9","key":"374_CR18","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1002\/ijc.27470","volume":"131","author":"A Tosovic","year":"2012","unstructured":"Tosovic A, Becker C, Bondeson AG, Bondeson L, Ericsson UB, Malm J, Manjer J (2012) Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk. Int J Cancer 131(9):2126\u20132133. https:\/\/doi.org\/10.1002\/ijc.27470","journal-title":"Int J Cancer"},{"issue":"10","key":"374_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047730","volume":"7","author":"AM Mondul","year":"2012","unstructured":"Mondul AM, Weinstein SJ, Bosworth T, Remaley AT, Virtamo J, Albanes D (2012) Circulating thyroxine, thyroid-stimulating hormone, and hypothyroid status and the risk of prostate cancer. PLoS One 7(10):e47730. https:\/\/doi.org\/10.1371\/journal.pone.0047730","journal-title":"PLoS One"},{"issue":"6","key":"374_CR20","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1002\/cncr.20881","volume":"103","author":"M Cristofanilli","year":"2005","unstructured":"Cristofanilli M, Yamamura Y, Kau SW, Bevers T, Strom S, Patangan M, Hsu L, Krishnamurthy S, Theriault RL, Hortobagyi GN (2005) Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer 103(6):1122\u20131128. https:\/\/doi.org\/10.1002\/cncr.20881","journal-title":"Cancer"},{"issue":"1","key":"374_CR21","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.cgh.2006.07.011","volume":"5","author":"A Reddy","year":"2007","unstructured":"Reddy A, Dash C, Leerapun A, Mettler TA, Stadheim LM, Lazaridis KN, Roberts RO, Roberts LR (2007) Hypothyroidism: a possible risk factor for liver cancer in patients with no known underlying cause of liver disease. Clin Gastroenterol Hepatol: the official clinical practice journal of the American Gastroenterological Association 5(1):118\u2013123. https:\/\/doi.org\/10.1016\/j.cgh.2006.07.011","journal-title":"Clin Gastroenterol Hepatol: the official clinical practice journal of the American Gastroenterological Association"},{"key":"374_CR22","doi-asserted-by":"crossref","unstructured":"Wippel C SA, Berghoff AS, Bergen E, Wolf P, Widhalm G, Frischer JM, Gatterbauer B, Marosi C, Dieckmann K, Bartsch R, Preusser M (2018) Hypothyroidism is associated with improved survival prognosis in patients with newly diagnosed brain metastases. https:\/\/oncologypro.esmo.org\/Meeting-Resources\/ESMO-2018-Congress\/Hypothyroidism-is-associated-with-improved-survival-prognosis-in-patients-with-newly-diagnosed-brain-metastases Accessed 10 October, 2019","DOI":"10.1093\/annonc\/mdy273.366"},{"issue":"3","key":"374_CR23","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s12672-018-0326-9","volume":"9","author":"A Hercbergs","year":"2018","unstructured":"Hercbergs A, Mousa SA, Leinung M, Lin HY, Davis PJ (2018) Thyroid hormone in the clinic and breast cancer. Horm Cancer 9(3):139\u2013143. https:\/\/doi.org\/10.1007\/s12672-018-0326-9","journal-title":"Horm Cancer"},{"issue":"11","key":"374_CR24","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1089\/thy.2005.15.1253","volume":"15","author":"Johannes L.P. Kuijpens","year":"2005","unstructured":"Kuijpens JLP, Nykl\u00ed\u010dtek I, Louwman MWJ, Weetman TAP, Pop DVJM, Coebergh J-WW (2005) Hypothyroidism might be related to breast cancer in post-menopausal women. 15(11):1253\u20131259. https:\/\/doi.org\/10.1089\/thy.2005.15.1253","journal-title":"Thyroid"},{"issue":"7","key":"374_CR25","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.tem.2009.03.011","volume":"20","author":"A Aranda","year":"2009","unstructured":"Aranda A, Martinez-Iglesias O, Ruiz-Llorente L, Garcia-Carpizo V, Zambrano A (2009) Thyroid receptor: roles in cancer. Trends Endocrinol Metab 20(7):318\u2013324. https:\/\/doi.org\/10.1016\/j.tem.2009.03.011","journal-title":"Trends Endocrinol Metab"},{"issue":"1","key":"374_CR26","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1634\/theoncologist.2013-0237","volume":"19","author":"Y Carter","year":"2014","unstructured":"Carter Y, Sippel RS, Chen H (2014) Hypothyroidism after a cancer diagnosis: etiology, diagnosis, complications, and management. Oncologist 19(1):34\u201343. https:\/\/doi.org\/10.1634\/theoncologist.2013-0237","journal-title":"Oncologist"},{"issue":"2","key":"374_CR27","first-page":"99","volume":"6","author":"K Hartmann","year":"2015","unstructured":"Hartmann K (2015) Thyroid disorders in the oncology patient. J Adv Pract Oncol 6(2):99\u2013106","journal-title":"J Adv Pract Oncol"},{"issue":"2","key":"374_CR28","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s10549-014-3256-4","volume":"149","author":"S de Groot","year":"2015","unstructured":"de Groot S, Janssen LG, Charehbili A, Dijkgraaf EM, Smit VT, Kessels LW, van Bochove A, van Laarhoven HW, Meershoek-Klein Kranenbarg E, van Leeuwen-Stok AE, van de Velde CJ, Putter H, Nortier JW, van der Hoeven JJ, Pijl H, Kroep JR (2015) Thyroid function alters during neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01). Breast Cancer Res Treat 149(2):461\u2013466. https:\/\/doi.org\/10.1007\/s10549-014-3256-4","journal-title":"Breast Cancer Res Treat"},{"issue":"4","key":"374_CR29","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1210\/jc.2017-01939","volume":"103","author":"A Hercbergs","year":"2018","unstructured":"Hercbergs A, Mousa SA, Davis PJ (2018) Nonthyroidal illness syndrome and thyroid hormone actions at integrin \u03b1v\u03b23. J Clin Endocrinol Metab 103(4):1291\u20131295. https:\/\/doi.org\/10.1210\/jc.2017-01939","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"374_CR30","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1634\/theoncologist.2014-0308","volume":"20","author":"A Hercbergs","year":"2015","unstructured":"Hercbergs A, Johnson RE, Ashur-Fabian O, Garfield DH, Davis PJ (2015) Medically induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study. Oncologist 20(1):72\u201376. https:\/\/doi.org\/10.1634\/theoncologist.2014-0308","journal-title":"Oncologist"},{"issue":"4","key":"374_CR31","doi-asserted-by":"publisher","first-page":"580","DOI":"10.4103\/2230-8210.113724","volume":"17","author":"Y Balhara","year":"2013","unstructured":"Balhara Y, Deb K (2013) Impact of alcohol use on thyroid function. Indian J Endocr Metab 17(4):580\u2013587. https:\/\/doi.org\/10.4103\/2230-8210.113724","journal-title":"Indian J Endocr Metab"},{"issue":"9742","key":"374_CR32","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/s0140-6736(10)61121-x","volume":"376","author":"YJ Bang","year":"2010","unstructured":"Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687\u2013697. https:\/\/doi.org\/10.1016\/s0140-6736(10)61121-x","journal-title":"Lancet"},{"issue":"1","key":"374_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10120-013-0252-z","volume":"17","author":"N Boku","year":"2014","unstructured":"Boku N (2014) HER2-positive gastric cancer. Gastric Cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 17(1):1\u201312. https:\/\/doi.org\/10.1007\/s10120-013-0252-z","journal-title":"Gastric Cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association"},{"issue":"1","key":"374_CR34","doi-asserted-by":"publisher","first-page":"54","DOI":"10.5603\/ep.2014.0008","volume":"65","author":"N Sawicka-Gutaj","year":"2014","unstructured":"Sawicka-Gutaj N, Gutaj P, Sowinski J, Wender-Ozegowska E, Czarnywojtek A, Brazert J, Ruchala M (2014) Influence of cigarette smoking on thyroid gland \u2013 an update. Endokrynol Pol 65(1):54\u201362. https:\/\/doi.org\/10.5603\/ep.2014.0008","journal-title":"Endokrynol Pol"}],"container-title":["Hormones and Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-019-00374-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12672-019-00374-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-019-00374-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,27]],"date-time":"2020-12-27T00:45:51Z","timestamp":1609029951000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12672-019-00374-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,28]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["374"],"URL":"https:\/\/doi.org\/10.1007\/s12672-019-00374-1","relation":{},"ISSN":["1868-8497","1868-8500"],"issn-type":[{"value":"1868-8497","type":"print"},{"value":"1868-8500","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,28]]},"assertion":[{"value":"13 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"HC.P. has received travel support from Eli Lilly, MSD, Novartis, Pfizer, and Roche.AS.B. has research support from Daiichi Sankyo and Roche; honoraria for lectures, consultation, or advisory board participation from Roche, Bristol-Myers Squibb, Merck, and Daiichi Sankyo; as well as travel support from Roche, Amgen, Daiichi Sankyo, and AbbVie. M.P. has received honoraria for lectures, consultation, or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp and Dohme.A.I-M. participated in advisory boards from MSD and Servier, received lecture honoraria from Eli Lilly and Servier, and is the local PI for clinical trials sponsored by BMS and Astellas.Other authors have nothing to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1964 and later versions. Due to the retrospective design, no separate informed consent was necessary in the scope of this study. The study was approved by the ethics committee of the Medical University of Vienna (signee J\u00fcrgen Zezula, reference number: 2267\/2016).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}