{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:06:39Z","timestamp":1780067199315,"version":"3.54.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T00:00:00Z","timestamp":1693094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T00:00:00Z","timestamp":1693094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims<\/jats:title>\n                <jats:p>To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (\u2265\u200965\u00a0years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12\u00a0months from starting treatment. We now reported the updated results after a median follow-up 76\u00a0months.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6\u00a0months, until 30\u00a0months from baseline, then yearly for at least 5\u00a0years.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203\/2011; EudraCT identification number: 2010-024067-41<jats:bold>,<\/jats:bold> for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18\u00a0months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84\u00a0months. At these time points, a statistically significant reduction of \u2212\u00a03.2%, \u2212\u00a04.6%, \u2212\u00a06.4% and \u2212\u00a07.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse\u00a0and,\u00a0 of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10238-023-01144-8","type":"journal-article","created":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T12:01:41Z","timestamp":1693137701000},"page":"5113-5120","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study"],"prefix":"10.1007","volume":"23","author":[{"given":"Luigi","family":"Coltelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Finale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Musettini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Barletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra Renata","family":"Lucarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Fabiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Scalese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Bocci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna Chiara","family":"Masini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Soria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Cupini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Arrighi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Barbara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ermelinda","family":"De Maio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Salvadori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Marini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pellino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Stasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Emdin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Giaconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Marcucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Allegrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,27]]},"reference":[{"issue":"1130","key":"1144_CR1","doi-asserted-by":"publisher","first-page":"20211033","DOI":"10.1259\/bjr.20211033","volume":"95","author":"L Wilkinson","year":"2022","unstructured":"Wilkinson L, Gathani T, et al. Understanding breast cancer as a global health concern. Br J Radiol. 2022;95(1130):20211033. https:\/\/doi.org\/10.1259\/bjr.20211033.","journal-title":"Br J Radiol"},{"issue":"6","key":"1144_CR2","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1586\/14737140.2016.1170595","volume":"16","author":"N Pond\u00e8","year":"2016","unstructured":"Pond\u00e8 N, Dal Lago L, et al. Adjuvant chemotherapy in elderly patients with breast cancer: key challenges. Expert Rev Anticancer Ther. 2016;16(6):661\u201371. https:\/\/doi.org\/10.1586\/14737140.2016.1170595.","journal-title":"Expert Rev Anticancer Ther"},{"key":"1144_CR3","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1007\/s11864-009-0092-6","volume":"10","author":"M Leung","year":"2009","unstructured":"Leung M, Shapira I, et al. Adjuvant chemotherapy for early breast cancer in the elderly. Curr Treat Options Oncol. 2009;10:144\u201358. https:\/\/doi.org\/10.1007\/s11864-009-0092-6.","journal-title":"Curr Treat Options Oncol"},{"key":"1144_CR4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.breast.2022.09.001","volume":"66","author":"Y Sang","year":"2022","unstructured":"Sang Y, Benlong Y, et al. Treatment and survival outcomes in older women with primary breast cancer: a retrospective propensity score-matched analysis. Breast. 2022;66:24\u201330. https:\/\/doi.org\/10.1016\/j.breast.2022.09.001.","journal-title":"Breast"},{"key":"1144_CR5","doi-asserted-by":"publisher","first-page":"e327","DOI":"10.1016\/S1470-2045(20)30741-5","volume":"22","author":"L Biganzoli","year":"2021","unstructured":"Biganzoli L, Battisti N, et al. Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European society of breast cancer specialists (EUSOMA) and the international society of geriatric oncology (SIOG). Lancet Oncol. 2021;22:e327\u201340. https:\/\/doi.org\/10.1016\/S1470-2045(20)30741-5.","journal-title":"Lancet Oncol"},{"issue":"2","key":"1144_CR6","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1177\/1074248420968689","volume":"26","author":"E Screever","year":"2021","unstructured":"Screever E, Meijers W, et al. Age-related considerations in cardio-oncology. J Cardiovasc Pharmacol Ther. 2021;26(2):103\u201313. https:\/\/doi.org\/10.1177\/1074248420968689.","journal-title":"J Cardiovasc Pharmacol Ther"},{"key":"1144_CR7","doi-asserted-by":"publisher","unstructured":"Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Peto R, Davies C et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet, 2012; 379 (9814): 432\u2013444. https:\/\/doi.org\/10.1016\/S0140-6736(11)61625-5.","DOI":"10.1016\/S0140-6736(11)61625-5"},{"issue":"34","key":"1144_CR8","doi-asserted-by":"publisher","first-page":"8597","DOI":"10.1200\/JCO.2005.02.5841","volume":"23","author":"JJ Doyle","year":"2005","unstructured":"Doyle JJ, Neugut AI, et al. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol. 2005;23(34):8597\u2013605. https:\/\/doi.org\/10.1200\/JCO.2005.02.5841.","journal-title":"J Clin Oncol"},{"issue":"5","key":"1144_CR9","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1007\/s00520-020-05766-6","volume":"29","author":"A Monteiro","year":"2021","unstructured":"Monteiro A, Garcia A, et al. Acute toxicity and tolerability of anthracycline-based chemotherapy regimens in older versus younger patients with breast cancer: real-world data. Support Care Cancer. 2021;29(5):2347\u201353. https:\/\/doi.org\/10.1007\/s00520-020-05766-6.","journal-title":"Support Care Cancer"},{"issue":"4","key":"1144_CR10","doi-asserted-by":"publisher","first-page":"853","DOI":"10.4103\/0973-1482.139267","volume":"10","author":"S Rivankar","year":"2014","unstructured":"Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther. 2014;10(4):853\u20138. https:\/\/doi.org\/10.4103\/0973-1482.139267.","journal-title":"J Cancer Res Ther"},{"key":"1144_CR11","doi-asserted-by":"publisher","unstructured":"Rafiyath SM, Rasu M et al. Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis. Exper Hematol Oncol 2012. https:\/\/doi.org\/10.1186\/2162-3619-1-10.","DOI":"10.1186\/2162-3619-1-10"},{"key":"1144_CR12","doi-asserted-by":"publisher","unstructured":"Van Dalen EC, Michiels EM et al. Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev, 2010; 18: (4): CD005006. https:\/\/doi.org\/10.1002\/14651858.CD005006.pub4.","DOI":"10.1002\/14651858.CD005006.pub4"},{"issue":"1","key":"1144_CR13","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1186\/s12885-021-09050-6","volume":"21","author":"J Zhang","year":"2021","unstructured":"Zhang J, Hongchuan J, et al. Effectiveness and safety of pegylated liposomal doxorubicin versus epirubicin as neoadjuvant or adjuvant chemotherapy for breast cancer: a real-world study. BMC Cancer. 2021;21(1):1301. https:\/\/doi.org\/10.1186\/s12885-021-09050-6.","journal-title":"BMC Cancer"},{"issue":"27","key":"1144_CR14","doi-asserted-by":"publisher","first-page":"4522","DOI":"10.1200\/JCO.2008.20.5013","volume":"27","author":"JA Sparano","year":"2009","unstructured":"Sparano JA, Makhson AN, et al. Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol. 2009;27(27):4522\u20139. https:\/\/doi.org\/10.1200\/JCO.2008.20.5013.","journal-title":"J Clin Oncol"},{"issue":"3","key":"1144_CR15","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s10549-015-3415-2","volume":"151","author":"MJ Gilgil","year":"2015","unstructured":"Gilgil MJ, Bellet M, et al. Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study. Breast Cancer Res Treat. 2015;151(3):597\u2013606. https:\/\/doi.org\/10.1007\/s10549-015-3415-2.","journal-title":"Breast Cancer Res Treat"},{"key":"1144_CR16","doi-asserted-by":"publisher","unstructured":"Gilgil MJ, Bellet M et al. Long-term cardiac safety and survival outcomes of neoadjuvant pegylated liposomal doxorubicin in elderly patients or prone to cardiotoxicity and triple negative breast cancer. Final results of the multicentre phase II CAPRICE study. Front Oncol. 2021 9;11:645026. https:\/\/doi.org\/10.3389\/fonc.2021.645026.","DOI":"10.3389\/fonc.2021.645026"},{"key":"1144_CR17","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.breast.2016.11.006","volume":"31","author":"L Coltelli","year":"2017","unstructured":"Coltelli L, Fontana A, et al. Cardiac safety of adjuvant non-pegylated liposomal doxorubicin combined with cyclophosphamide and followed by paclitaxel in older breast cancer patients. Breast. 2017;31:186\u201391. https:\/\/doi.org\/10.1016\/j.breast.2016.11.006.","journal-title":"Breast"},{"issue":"3","key":"1144_CR18","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1634\/theoncologist.5-3-224","volume":"5","author":"L Balducci","year":"2000","unstructured":"Balducci L, Extermann M, et al. Management of cancer in the older person: a practical approach. Oncologist. 2000;5(3):224\u201337. https:\/\/doi.org\/10.1634\/theoncologist.5-3-224.","journal-title":"Oncologist"},{"key":"1144_CR19","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1002\/sim.721","volume":"20","author":"RP A'Hern","year":"2001","unstructured":"A\u2019Hern RP. Sample size tables for exact single-stage phase II designs. Statist Med. 2001;20:859\u201366. https:\/\/doi.org\/10.1002\/sim.721.","journal-title":"Statist Med"},{"key":"1144_CR20","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE) v3.0. National Cancer Institute. http:\/\/ctep.cancer.gov\/reporting\/ctc.html."},{"issue":"8","key":"1144_CR21","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s41569-020-0348-1","volume":"17","author":"J Herrmann","year":"2020","unstructured":"Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nat Rev Cardiol. 2020;17(8):474\u2013502. https:\/\/doi.org\/10.1038\/s41569-020-0348-1.","journal-title":"Nat Rev Cardiol"},{"key":"1144_CR22","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1093\/annonc\/mdf284","volume":"13","author":"H Gogas","year":"2002","unstructured":"Gogas H, Papadimitriou C, et al. Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx\u00ae) and paclitaxel in locally advanced breast cancer: a phase II study by the hellenic cooperative oncology group. Ann Oncol. 2002;13:1737\u201342. https:\/\/doi.org\/10.1093\/annonc\/mdf284.","journal-title":"Ann Oncol"},{"issue":"1","key":"1144_CR23","doi-asserted-by":"publisher","first-page":"18135","DOI":"10.1038\/s41598-019-54387-5","volume":"9","author":"R Li","year":"2019","unstructured":"Li R, Tian F, et al. Pegylated liposomal doxorubicin plus cyclophosphamide followed by docetaxel as neoadjuvant chemotherapy in locally advanced breast cancer. Sci Rep. 2019;9(1):18135. https:\/\/doi.org\/10.1038\/s41598-019-54387-5.","journal-title":"Sci Rep"},{"key":"1144_CR24","doi-asserted-by":"publisher","first-page":"4247","DOI":"10.2147\/OTT.S162003","volume":"11","author":"M Dong","year":"2018","unstructured":"Dong M, Luo L, et al. Comparable efficacy and less toxicity of pegylated liposomal doxorubicin versus epirubicin for neoadjuvant chemotherapy of breast cancer: a case-control study. Onco Targets Ther. 2018;11:4247\u201352. https:\/\/doi.org\/10.2147\/OTT.S162003.","journal-title":"Onco Targets Ther"},{"issue":"41","key":"1144_CR25","doi-asserted-by":"publisher","first-page":"4229","DOI":"10.1093\/eurheartj\/ehac244","volume":"43","author":"AR Lyon","year":"2022","unstructured":"Lyon AR, L\u00f2pez-F\u00e8rnandez T, et al. ESC guidelines on cardio-oncology developed in collaboration with the European hematology association (EHA), the European society for therapeutic radiology and oncology (ESTRO) and the international cardio-oncology society (IC-OS). Eur Heart J. 2022;43(41):4229\u2013361. https:\/\/doi.org\/10.1093\/eurheartj\/ehac244.","journal-title":"Eur Heart J"},{"issue":"4","key":"1144_CR26","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.jacc.2020.11.020","volume":"77","author":"P Thavendiranathan","year":"2021","unstructured":"Thavendiranathan P, Negishi T, et al. Strain-guided management of potentially cardiotoxic cancer therapy. J Am Coll Cardiol. 2021;77(4):392\u2013401. https:\/\/doi.org\/10.1016\/j.jacc.2020.11.020.","journal-title":"J Am Coll Cardiol"},{"key":"1144_CR27","doi-asserted-by":"publisher","unstructured":"Oikonomou, EK, Kokkinidis DG et al. Assessment of prognostic value of left ventricular global longitudinal strain for early prediction of chemotherapy-induced cardiotoxicity. A systematic review and meta-analysis. JAMA Cardiol. 2019;4(10):1007\u20131018. https:\/\/doi.org\/10.1001\/jamacardio.2019.2952.","DOI":"10.1001\/jamacardio.2019.2952"},{"issue":"2","key":"1144_CR28","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/ejhf.1631","volume":"22","author":"L Michel","year":"2020","unstructured":"Michel L, Mincu RI, et al. Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis. Eur J Heart Fail. 2020;22(2):350\u201361. https:\/\/doi.org\/10.1002\/ejhf.1631.","journal-title":"Eur J Heart Fail"},{"issue":"2","key":"1144_CR29","doi-asserted-by":"publisher","first-page":"e014708","DOI":"10.1161\/JAHA.119.014708","volume":"9","author":"BG Demissei","year":"2020","unstructured":"Demissei BG, Hubbard RA, et al. Changes in cardiovascular biomarkers with breast cancer therapy and associations with cardiac dysfunction. J Am Heart Assoc. 2020;9(2):e014708. https:\/\/doi.org\/10.1161\/JAHA.119.014708.","journal-title":"J Am Heart Assoc"},{"issue":"Suppl 2","key":"1144_CR30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1634\/theoncologist.8-suppl_2-17","volume":"8","author":"T Safra","year":"2003","unstructured":"Safra T. Cardiac safety of liposomal anthracyclines. Oncologist. 2003;8(Suppl 2):17\u201324. https:\/\/doi.org\/10.1634\/theoncologist.8-suppl_2-17.","journal-title":"Oncologist"},{"key":"1144_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/2162-3619-1-10","author":"MR Shamudheen","year":"2012","unstructured":"Shamudheen MR, Mohammad R, et al. Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis. Exp Hematol Oncol. 2012. https:\/\/doi.org\/10.1186\/2162-3619-1-10.","journal-title":"Exp Hematol Oncol"},{"issue":"4","key":"1144_CR32","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/jebm.12506","volume":"15","author":"Y Wu","year":"2022","unstructured":"Wu Y, Yang Q, et al. Effect of adjuvant chemotherapy on the survival outcomes of elderly breast cancer: a retrospective cohort study based on SEER database. J Evid Based Med. 2022;15(4):354\u201364. https:\/\/doi.org\/10.1111\/jebm.12506.","journal-title":"J Evid Based Med"},{"issue":"4","key":"1144_CR33","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1093\/annonc\/mdu564","volume":"26","author":"F Perrone","year":"2015","unstructured":"Perrone F, Nuzzo F, et al. Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial. Ann Oncol. 2015;26(4):675\u201382. https:\/\/doi.org\/10.1093\/annonc\/mdu564.","journal-title":"Ann Oncol"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-023-01144-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-023-01144-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-023-01144-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T16:13:06Z","timestamp":1702743186000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-023-01144-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,27]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1144"],"URL":"https:\/\/doi.org\/10.1007\/s10238-023-01144-8","relation":{},"ISSN":["1591-9528"],"issn-type":[{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,27]]},"assertion":[{"value":"18 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The present work was supported by The Fondazione per le Attivit\u00e0 di Ricerca in Oncologia (F.A.R.O.) of Pontedera, Pisa, (Italy). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. No writing assistance was utilized in the production of this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee authorization CESM-AOUP, 3203\/2011; EudraCT identification number: 2010\u2013024067-41<b>,<\/b> for Pisa and Pontedera Hospitals.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}