Onkologie. 2024:18(4):237-243 | DOI: 10.36290/xon.2024.049

Locoregionally advanced carcinoma of gastroesophageal junction and stomach: past, present, future

Marián Liberko1, 2, Renata Soumarová1, 2
1 Onkologická klinika, 3. LF UK a FNKV, Praha
2 3. lékařská fakulta Univerzity Karlovy, Praha

Given the high incidence of gastroesophageal junction (OGJ) and gastric tumours globally, they represent a major medical problem. The majority of these diseases are diagnosed at a locoregionally advanced and/or metastatic stage, which requires a comprehensive multidisciplinary approach. The mainstay of treatment of locoregionally advanced stages is systemic perioperative therapy, which has been shown to improve patient prognosis. With the aim of further improvement, standard periope­rative chemotherapy is combined with immunotherapy. The aim of this review is to provide an overview of current recommendations and new treatment guidelines for locoregionally advanced stages of OGJ and gastric cancer.

Keywords: gastroesophageal junction tumours, gastric tumours, perioperative chemotherapy, FLOT, immunotherapy.

Accepted: October 1, 2024; Published: October 7, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Liberko M, Soumarová R. Locoregionally advanced carcinoma of gastroesophageal junction and stomach: past, present, future. Onkologie. 2024;18(4):237-243. doi: 10.36290/xon.2024.049.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • PDF will be unlocked 7.10.2025

    References

    1. Ferlay J, Ervik M, Colombet M, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today. Published 2022. Accessed May 19, 2024.
    2. GBD 2017 Stomach Cancer Collaborators. The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol Hepatol. 2020;5(1):42-54. doi: 10.1016/S2468-1253(19)30328-0. Epub 2019 Oct 21. Erratum in: Lancet Gastroenterol Hepatol. 2020;5(3):e2. PMID: 31648970; PMCID: PMC7033564. Go to original source... Go to PubMed...
    3. Colquhoun A, Arnold M, Ferlay J, et al. Global patterns of cardia and non-cardia gastric cancer incidence in 2012. Gut. 2015;64(12):1881-1888. doi: 10.1136/gutjnl-2014-308915. Epub 2015 Mar 6. PMID: 25748648. Go to original source... Go to PubMed...
    4. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015;47(9):829-854. doi: 10.1055/s-0034-1392882. Epub 2015 Aug 28. PMID: 26317585. Go to original source... Go to PubMed...
    5. Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(10):1005-1020. doi: 10.1016/j.annonc.2022.07.004. Epub 2022 Jul 29. PMID: 35914639. Go to original source... Go to PubMed...
    6. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11-20. doi: 10.1056/NEJMoa055531. PMID: 16822992. Go to original source... Go to PubMed...
    7. Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastro­esophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715-1721. doi: 10.1200/JCO.2010.33.0597. Epub 2011 Mar 28. PMID: 21444866. Go to original source... Go to PubMed...
    8. Alderson D, Cunningham D, Nankivell M, et al. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017;18(9):1249-1260. doi: 10.1016/S1470-2045(17)30447-3. Epub 2017 Aug 4. PMID: 28784312; PMCID: PMC5585417. Go to original source... Go to PubMed...
    9. Al-Batran SE, Homann N, Pauligk C, 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):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11. PMID: 30982686. Go to original source... Go to PubMed...
    10. Smyth EC, Fassan M, Cunningham D, et al. Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. J Clin Oncol. 2016;34(23):2721-2727. doi: 10.1200/JCO.2015.65.7692. Epub 2016 Jun 13. PMID: 27298411; PMCID: PMC5019747. Go to original source... Go to PubMed...
    11. Rahman S, Thomas B, Maynard N, et al. Impact of postoperative chemotherapy on survival for oesophagogastric adenocarcinoma after preoperative chemotherapy and surgery. Br J Surg. 2022;109(2):227-236. doi: 10.1093/bjs/znab427. PMID: 34910129; PMCID: PMC10364695. Go to original source... Go to PubMed...
    12. Smyth E, Mauer M, Cella C, et al. O-6 EORTC 1707 VESTIGE: Adjuvant immunotherapy in patients (pts) with resected gastro­esophageal adenocarcinoma (GEA) following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1) an open-label randomized controlled phase II study. Annals of Oncology. 2023;34:S182-S183. https://doi.org/10.1016/j.annonc.2023.04.021. Go to original source...
    13. Cats A, Jansen EPM, van Grieken NCT, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):616-628. doi: 10.1016/S1470-2045(18)30132-3. Epub 2018 Apr 9. PMID: 29650363. Go to original source... Go to PubMed...
    14. de Steur WO, van Amelsfoort RM, Hartgrink HH, et al. Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial. Ann Oncol. 2021;32(3):360-367. doi: 10.1016/j.annonc.2020.11.004. Epub 2020 Nov 20. PMID: 33227408. Go to original source... Go to PubMed...
    15. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neo­adjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5. PMID: 26254683. Go to original source... Go to PubMed...
    16. Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol. 2021;39(18):1995-2004. doi: 10.1200/JCO.20.03614. Epub 2021 Apr 23. PMID: 33891478. Go to original source... Go to PubMed...
    17. Reynolds JV, Preston SR, O'Neill B, et al. Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial. Lancet Gastroenterol Hepatol. 2023;8(11):1015-1027. doi: 10.1016/S2468-1253(23)00243-1. Epub 2023 Sep 18. PMID: 37734399; PMCID: PMC10567579. Go to original source... Go to PubMed...
    18. Hoeppner J, Brunner T, Lordick F, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial). JCO. 2024;42:LBA1-LBA1. doi: 10.1200/JCO.2024.42.17_suppl.LBA1. Go to original source...
    19. Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379(9813):315-321. doi: 10.1016/S0140-6736(11)61873-4. Epub 2012 Jan 7. PMID: 22226517. Go to original source... Go to PubMed...
    20. Noh SH, Park SR, Yang HK, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(12):1389-1396. doi: 10.1016/S1470-2045(14)70473-5. Epub 2014 Oct 15. PMID: 25439693. Go to original source... Go to PubMed...
    21. Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810-1820. doi: 10.1056/NEJMoa072252. Erratum in: N Engl J Med. 2008;358(18):1977. PMID: 17978289. Go to original source... Go to PubMed...
    22. Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29(33):4387-4393. doi: 10.1200/JCO.2011.36.5908. Epub 2011 Oct 17. PMID: 22010012. Go to original source... Go to PubMed...
    23. Kakeji Y, Yoshida K, Kodera Y, et al. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in sta­ge III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022;25(1):188-196. doi: 10.1007/s10120-021-01224-2. Epub 2021 Aug 5. PMID: 34351555. Go to original source... Go to PubMed...
    24. GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group; Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, Van Cutsem E, Buyse M. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303(17):1729-1737. doi: 10.1001/jama.2010.534. PMID: 20442389. Go to original source... Go to PubMed...
    25. Terashima M, Kang YK, Kim YW, et al. ATTRACTION-5: A phase 3 study of nivolumab plus chemotherapy as postoperative adjuvant treatment for pathological stage III (pStage III) gastric or gastroesophageal junction (G/GEJ) cancer. JCO. 2023;41:4000-4000. doi: 10.1200/JCO.2023.41.16_suppl.4000. Go to original source...
    26. Lee J, Lim DH, Kim S, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30(3):268-273. doi: 10.1200/JCO.2011.39.1953. Epub 2011 Dec 19. PMID: 22184384. Go to original source... Go to PubMed...
    27. Park SH, Lim DH, Sohn TS, et al. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆. Ann Oncol. 2021;32(3):368-374. doi: 10.1016/j.annonc.2020.11.017. Epub 2020 Dec 3. PMID: 33278599. Go to original source... Go to PubMed...
    28. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725-730. doi: 10.1056/NEJMoa010187. PMID: 11547741. Go to original source... Go to PubMed...
    29. Smalley SR, Benedetti JK, Haller DG, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30(19):2327-2333. doi: 10.1200/JCO.2011.36.7136. Epub 2012 May 14. PMID: 22585691; PMCID: PMC4517071. Go to original source... Go to PubMed...
    30. Dikken JL, Jansen EP, Cats A, et al. Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin Oncol. 2010;28(14):2430-2436. doi: 10.1200/JCO.2009.26.9654. Epub 2010 Apr 5. PMID: 20368551. Go to original source... Go to PubMed...
    31. Bang YJ, Van Cutsem E, Feyereislova A, et al. 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. 2010;376(9742):687-697. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19. Erratum in: Lancet. 2010;376(9749):1302. PMID: 20728210. Go to original source... Go to PubMed...
    32. Hofheinz RD, Hegewisch-Becker S, Kunzmann V, et al. Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group. Int J Cancer. 2021;149(6):1322-1331. doi: 10.1002/ijc.33696. Epub 2021 May 29. PMID: 34019698. Go to original source... Go to PubMed...
    33. Hofheinz RD, Merx K, Haag GM, et al. FLOT Versus FLOT/Trastuzumab/Pertuzumab Perioperative Therapy of Human Epidermal Growth Factor Receptor 2-Positive Resectable Esophagogastric Adenocarcinoma: A Randomized Phase II Trial of the AIO EGA Study Group. J Clin Oncol. 2022;40(32):3750-3761. doi: 10.1200/JCO.22.00380. Epub 2022 Jun 16. PMID: 35709415. Go to original source... Go to PubMed...
    34. Wagner AD, Grabsch HI, Mauer M, et al. Integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy (CT) of HER-2 positive gastric (GC) and esophagogastric junction cancer (EGJC): First results of the EORTC 1203 INNOVATION study, in collaboration with the Korean Can­cer Study Group, and the Dutch Upper GI Cancer group. JCO. 2023;41:4057-4057. doi: 10.1200/JCO.2023.41.16_suppl.4057. Go to original source...
    35. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31-39. doi: 10.1016/S0140-6736(13)61719-5. Epub 2013 Oct 3. PMID: 24094768. Go to original source... Go to PubMed...
    36. Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. doi: 10.1016/S1470-2045(14)70420-6. Epub 2014 Sep 17. PMID: 25240821.Další literatura u autora a na www.onkologiecs.cz Go to original source... Go to PubMed...
    37. Goetze TO, Hofheinz RD, Gaiser T, et al. Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM. Int J Cancer. 2023;153(1):153-163. doi: 10.1002/ijc.34495. Epub 2023 Mar 23. PMID: 36883420. Go to original source... Go to PubMed...
    38. Lorenzen S, Götze TO, Thuss-Patience P, 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):410-420. doi: 10.1200/JCO.23.00975. Epub 2023 Nov 14. PMID: 37963317. Go to original source... Go to PubMed...
    39. Oh DY, Janjigian YY, Al-Batran SE, et al. 129O Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study. Annals of Oncology. 2023;34:S1520-S1521. https://doi.org/10.1016/j.annonc.2023.10.265. Go to original source...
    40. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastro-oesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study. 2023 European Society for Medical Oncology Congress 2023; Oct 20-24, abstr LBA73. Go to original source...
    41. Shitara K, Rha SY, Wyrwicz LS, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024;25(2):212-224. doi: 10.1016/S1470-2045(23)00541-7. Epub 2023 Dec 19. PMID: 38134948. Go to original source... Go to PubMed...
    42. Verschoor YL, van de Haar J, van den Berg JG, et al. Neo­adjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nat Med. 2024;30(2):519-530. doi: 10.1038/s41591-023-02758-x. Epub 2024 Jan 8. Erratum in: Nat Med. 2024 Mar 6. PMID: 38191613; PMCID: PMC10878980. Go to original source... Go to PubMed...
    43. André T, Tougeron D, Piessen G, et al. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study. J Clin Oncol. 2023;41(2):255-265. doi: 10.1200/JCO.22.00686. Epub 2022 Aug 15. PMID: 35969830; PMCID: PMC9839243. Go to original source... Go to PubMed...
    44. Pietrantonio F, Raimondi A, Lonardi S, et al. INFINITY: A multicentre, single-arm, multi-cohort, phase II trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability-high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC). JCO. 2023;41:358-358(2023). doi :10.1200/JCO.2023.41.4_suppl.358. Go to original source...

    Return to the content


    Oncology

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.