{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:00:11Z","timestamp":1792414811226,"version":"4.4.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Schleswig-Holstein - Campus Kiel"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Since the FLOT4 gastric cancer (GC) trial, the use of adjuvant chemotherapy has been perceived as limited and its added value questioned. We wanted to objectify this perception and reassess the value of adjuvant chemotherapy in a real-world setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In our retrospective cohort study we analyzed real-world data from 147 patients with GC or cancer of the gastroesophageal junction (AEG) who received perioperative FLOT. Data originated from clinical care at the university hospital, local hospitals and medical practices. Clinicopathologic data, survival outcomes, and targetable biomarkers were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median overall survival (OS) and tumor specific survival (TSS) were 19.4\u2009\u00b1\u20092.9 and 19.9\u2009\u00b1\u20093.1 months, respectively. 84.4% completed all cycles of neoadjuvant chemotherapy. The pathological complete response rate was 11.8%. Adjuvant chemotherapy was initiated in only 42.9%. Survival rates of patients with marked tumor regression (TRG1) were not improved by adjuvant chemotherapy. Conversely, patients with partial histopathologic response (TRG2) showed a marked trend and those with minimal histopathologic response (TRG3) showed a significantly longer survival with any number of adjuvant chemotherapy cycles (OS: 22.3\u2009\u00b1\u20092.6 months versus 8.7\u2009\u00b1\u20092.4 months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005; TSS: 22.3\u2009\u00b1\u20094.5 months versus 8.7\u2009\u00b1\u20092.4 months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016). Targetable biomarkers PD-L1, Claudin 18.2, HER2 and microsatellite instability were detected in 53.4%, 26.2%, 7.8%, and 3.9% of the TRG2\/3 patient subset, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the real-world setting, adjuvant chemotherapy proved to be a critical turning point of the FLOT regimen. It should be sought\u2014even in a reduced form\u2014in patients with TRG2\/3.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10120-025-01624-8","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T15:07:00Z","timestamp":1747408020000},"page":"982-992","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Impact of adjuvant therapy on outcomes of cancer of the stomach and gastroesophageal junction in the real-world"],"prefix":"10.1007","volume":"28","author":[{"given":"Steffen M.","family":"Heckl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Michael","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Ebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dita","family":"Ulase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Letsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6989-8002","authenticated-orcid":false,"given":"Christoph","family":"R\u00f6cken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"1624_CR1","unstructured":"Varon C, Megraud F. Stomach cancer: still one of the main cancer types worldwide. Wild CP, Weiderpass E, Steward BW, editors. Lyon: International Agency for Research on Cancer; 2020. p. 10."},{"issue":"1","key":"1624_CR2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa055531","volume":"355","author":"D Cunningham","year":"2006","unstructured":"Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11\u201320.","journal-title":"N Engl J Med"},{"issue":"10184","key":"1624_CR3","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1016\/S0140-6736(18)32557-1","volume":"393","author":"SE Al-Batran","year":"2019","unstructured":"Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2\/3 trial. Lancet. 2019;393(10184):1948\u201357.","journal-title":"Lancet"},{"issue":"7","key":"1624_CR4","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1002\/cncr.11660","volume":"98","author":"K Becker","year":"2003","unstructured":"Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98(7):1521\u201330.","journal-title":"Cancer"},{"issue":"2","key":"1624_CR5","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41416-022-02047-3","volume":"128","author":"M Kock Am Brink","year":"2023","unstructured":"Kock Am Brink M, Dunst LS, Behrens HM, Kruger S, Becker T, Rocken C. Intratumoral heterogeneity affects tumor regression and Ki67 proliferation index in perioperatively treated gastric carcinoma. Br J Cancer. 2023;128(2):375\u201386.","journal-title":"Br J Cancer"},{"issue":"1","key":"1624_CR6","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-033323","volume":"10","author":"L Lou","year":"2020","unstructured":"Lou L, Wang L, Zhang Y, Chen G, Lin L, Jin X, et al. Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017. BMJ Open. 2020;10(1): e033323.","journal-title":"BMJ Open"},{"key":"1624_CR7","doi-asserted-by":"crossref","unstructured":"Bartel M, Brahmbhatt M, Bhurwal A. Incidence of gastroesophageal junction cancer continues to rise: analysis of surveillance, epidemiology, and end results (SEER) database. J Clin Oncol. 2019;37.","DOI":"10.1200\/JCO.2019.37.4_suppl.40"},{"key":"1624_CR8","doi-asserted-by":"crossref","unstructured":"Janjigian Y, Al-Batran S-E, Wainberg ZA, Van Cutsem E, Molena D, Muro K, et al. Pathological complete response (pCR) to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) with or without durvalumab (D) in resectable gastric and gastroesophageal junction cancer (GC\/GEJC): Subgroup analysis by region from the phase 3, randomized, double-blind MATTERHORN study. J Clin Oncol. 2024;42.","DOI":"10.1200\/JCO.2024.42.3_suppl.LBA246"},{"issue":"12","key":"1624_CR9","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1016\/S1470-2045(16)30531-9","volume":"17","author":"SE Al-Batran","year":"2016","unstructured":"Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2\/3 trial. Lancet Oncol. 2016;17(12):1697\u2013708.","journal-title":"Lancet Oncol"},{"issue":"4","key":"1624_CR10","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1200\/JCO.23.00975","volume":"42","author":"S Lorenzen","year":"2024","unstructured":"Lorenzen S, Gotze TO, Thuss-Patience P, Biebl M, Homann N, Schenk M, et al. Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: interim results from the randomized, multicenter, phase II\/III DANTE\/IKF-s633 trial. J Clin Oncol. 2024;42(4):410\u201320.","journal-title":"J Clin Oncol"},{"key":"1624_CR11","unstructured":"Investigators S-F. Pathological response guides adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in surgically resected gastro-oesophageal cancer (SPACE-FLOT): international cohort study. Br J Surg. 2025;112(4)."},{"issue":"11","key":"1624_CR12","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.35340","volume":"4","author":"L Deng","year":"2021","unstructured":"Deng L, Groman A, Jiang C, Perimbeti S, Gabriel E, Kukar M, et al. Association of preoperative chemosensitivity with postoperative survival in patients with resected gastric adenocarcinoma. JAMA Netw Open. 2021;4(11): e2135340.","journal-title":"JAMA Netw Open"},{"issue":"7","key":"1624_CR13","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1002\/jso.24601","volume":"115","author":"JH Saunders","year":"2017","unstructured":"Saunders JH, Bowman CR, Reece-Smith AM, Pang V, Dorrington MS, Mumtaz E, et al. The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery. J Surg Oncol. 2017;115(7):821\u20139.","journal-title":"J Surg Oncol"},{"issue":"10","key":"1624_CR14","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.ejso.2015.07.010","volume":"41","author":"T Glatz","year":"2015","unstructured":"Glatz T, Bronsert P, Schafer M, Kulemann B, Marjanovic G, Sick O, et al. Perioperative platin-based chemotherapy for locally advanced esophagogastric adenocarcinoma: Postoperative chemotherapy has a substantial impact on outcome. Eur J Surg Oncol. 2015;41(10):1300\u20137.","journal-title":"Eur J Surg Oncol"},{"key":"1624_CR15","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.humpath.2020.11.001","volume":"108","author":"G Saliba","year":"2021","unstructured":"Saliba G, Detlefsen S, Carneiro F, Conner J, Dorer R, Flejou JF, et al. Tumor regression grading after neoadjuvant treatment of esophageal and gastroesophageal junction adenocarcinoma: results of an international Delphi consensus survey. 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Transl Oncol. 2020;13(2):165\u201376.","journal-title":"Transl Oncol"},{"issue":"2","key":"1624_CR18","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.annonc.2024.10.829","volume":"36","author":"F Lordick","year":"2025","unstructured":"Lordick F, Mauer ME, Stocker G, Cella CA, Ben-Aharon I, Piessen G, et al. Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and\/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study. Ann Oncol. 2025;36(2):197\u2013207.","journal-title":"Ann Oncol"}],"container-title":["Gastric Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01624-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10120-025-01624-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01624-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T14:54:29Z","timestamp":1757170469000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10120-025-01624-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1624"],"URL":"https:\/\/doi.org\/10.1007\/s10120-025-01624-8","relation":{},"ISSN":["1436-3291","1436-3305"],"issn-type":[{"value":"1436-3291","type":"print"},{"value":"1436-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]},"assertion":[{"value":"10 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"AL received payment or honoraria from Astra Zeneca, Bayer, BMS, B\u00f6hringer Ingelheim, Gr\u00fcnenthal, Janssen, Lilly, MSD, Novartis, Roche, Servier and Tesaro. AL participates on the advisory boards of MSD, BMS and Lilly. AL has a leadership role in the Board of Directors European Association of Palliative Care (2023\u20132026) and in the ESMO Supportive and Palliative Care Faculty (2023\u20132026). All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures followed were in accordance with the ethical standards of the ethics committee [D453\/10 (22.10.2010); D525\/15 (20.08.2015)] of the University Hospital Schleswig\u2013Holstein, Kiel, Germany, which allowed us to use samples from those patients who had also given written informed consent for prospective scientific use of their patient material (broad consent). The study was performed in compliance with all relevant laws and institutional guidelines and in accordance with the code of ethics of the Helsinki Declaration of 1964 and later versions.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}