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Multimodal treatment in locally advanced gastric cancer

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Abstract

According to the data of the GLOBOCAN-network of the World Health Organization, there were 952,000 (6.8% of the total) new cases of gastric cancer in 2012, making it the fifth most common malignancy in the world. It represents a substantive change since the very first estimates in 1975 when stomach cancer was the most common neoplasm. More than 70% of cases (677,000 cases) occur in developing countries, and half the world total occurs in Eastern Asia, mainly in China. Gastric cancer is the third leading cause of cancer death in both sexes worldwide (Globocan, Estimated cancer incidence, mortality and prevalence worldwide in 2012, http://globocan.iarc.fr, 2012). Annually, worldwide 723,000 patients die of this tumor entity. Interestingly, a strong change in incidence rates in relation to the anatomical–topographic localization of the primary tumors in the stomach and esophagus has been experienced. While the frequency of proximal gastric carcinoma and adenocarcinoma of the cardiac and subcardiac region in Europe and North America has been constantly rising, distal gastric carcinomas have become less common (Torre et al. in JAMA 65:87–108, 2015). Furthermore, the relative incidence of esophageal adenocarcinoma (mostly localized in the distal esophagus) has strongly increased (Jemal et al. in JAMA 58:71–96, 2008; Crew and Neugut 31:450–464, 2004; Pohl and Welch 97:142–146, 2005).

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References

  1. Globocan (2012) Estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr

  2. Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics 2012. CA Cancer J Clin 65:87–108

    Article  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics. CA Cancer J Clin 58:71–96

    Article  PubMed  Google Scholar 

  4. Crew KD, Neugut AI (2004) Epidemiology of upper gastrointestinal malignancies. Semin Oncol 31:450–464

    Article  PubMed  Google Scholar 

  5. Pohl H, Welch HG (2005) The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 97:142–146

    Article  PubMed  Google Scholar 

  6. Cunningham D, Allum WH, Stenning SP (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20

    Article  PubMed  CAS  Google Scholar 

  7. Ychou M, Boige V, Pignon JP et al (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29:1715–1721

    Article  PubMed  CAS  Google Scholar 

  8. Songun I, Putter H, Kranenbarg EM et al (2010) Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 11:439–449

    Article  PubMed  Google Scholar 

  9. Wittekind C (2010) TNM-Klassifikation maligner Tumoren. 7. Auflage. Wiley-VCH, Weinheim

  10. Wagner PK, Ramaswamy A, Ruschoff J et al (1991) Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer. Br J Surg 78:825–827

    Article  PubMed  CAS  Google Scholar 

  11. Waddell T, Verheij M, Allum W et al (2013) Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6):57–63

    Article  Google Scholar 

  12. Moehler M, Al-Batran SE, Andus T et al (2011) German S3-guideline “diagnosis and treatment of esophagogastric cancer”. Z Gastroenterol 49:461–531

    Article  PubMed  CAS  Google Scholar 

  13. Alderson D, Langley RE, Nankivell MG (2015) Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072). J Clin Oncol 33(Suppl. 15):4002

    Google Scholar 

  14. Al-Batran SE, Hofheinz RD, Pauligk C et al (2016) 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 17:1697–1708

    Article  PubMed  CAS  Google Scholar 

  15. Al-Batran SE, Homann N, Schmalenberg H et al (2017) Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial. J Clin Oncol 35(Suppl. 15):4004

    Article  Google Scholar 

  16. Hofheinz R, Hegewisch-Becker S, Thuss-Patience P (2014) HER-FLOT: trastuzumab in combination with FLOT as perioperative treatment for patients with HER2-positive locally advanced esophagogastric adenocarcinoma: a phase II trial of the AIO Gastric Cancer Study Group. J Clin Oncol 32(Suppl. 5):4073

    Google Scholar 

  17. Fuchs CS, Tepper J, Niedzwiecki D et al (2011) Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: intergroup trial CALGB 80101. J Clin Oncol 29(Suppl. 15):4003

    Article  Google Scholar 

  18. Wilke H, Muro K, van Cutsem E et al (2014) 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 15:1224–1235

    Article  PubMed  CAS  Google Scholar 

  19. Ohtsu A, Shah MA, Van Cutsem E et al (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29:3968–3976

    Article  PubMed  CAS  Google Scholar 

  20. Shen L, Li J, Xu J et al (2015) Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastr Cancer 18:168–176

    Article  CAS  Google Scholar 

  21. Yoon HH, Bendell JC, Braiteh FS et al (2016) Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter phase II trial. Ann Oncol. https://doi.org/10.1093/annonc/mdw423

    Article  PubMed Central  PubMed  Google Scholar 

  22. Cunningham D, Stenning SP, Smyth EC et al (2017) Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial. Lancet Oncol 18:357–370

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Lordick F, Kang YK, Chung HC et al (2013) Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 14:490–499

    Article  PubMed  CAS  Google Scholar 

  24. Ilson DH, SuntharalingamJM Mohan, Dicker A et al (2014) RTOG 0436: a phase III trial evaluating the addition of cetuximab to paclitaxel, cisplatin, and radiation for patients with esophageal cancer treated without surgery. J Clin Oncol 32(Suppl. 15):4007

    Google Scholar 

  25. Kang YK, Ryu MH, Chao Y et al (2017) Nivolumab (ONO-4538/BMS-936558) as salvage treatment after second or later-line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): a double-blinded, randomized, phase III trial. J Clin Oncol 35(Suppl. 4):2

    Article  Google Scholar 

  26. Stahl M, Walz MK, Stuschke M et al (2009) Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27:851–856

    Article  PubMed  CAS  Google Scholar 

  27. Burmeister BH, Thomas JM, Burmeister EA et al (2011) Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer 47:354–360

    Article  PubMed  Google Scholar 

  28. Shapiro J, van Lanschot JJ, Hulshof MC et al (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16:1090–1098

    Article  PubMed  Google Scholar 

  29. Leichman LP, Bohanes PO, Lenz HJ et al (2011) A phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma. J Clin Oncol 29:4555–4560

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Ajani JA, Xiao L, Roth JA et al (2013) A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol 24:2844–2849

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Sjoquist KM, Burmeister BH, Smithers BM et al (2011) Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 12:681–692

    Article  PubMed  Google Scholar 

  32. Paoletti X, Ob K, Burzykowski T et al (2010) Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA 303:1729–1737

    Article  PubMed  CAS  Google Scholar 

  33. Sasako M, Sakuramoto S, Katai H et al (2011) 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 29:4387–4393

    Article  PubMed  CAS  Google Scholar 

  34. Noh SH, Park SR, Yang HK et al (2014) 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 15:1389–1396

    Article  PubMed  CAS  Google Scholar 

  35. Bajetta E, Floriani I, Di Bartolomeo M et al (2014) Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer. Ann Oncol 25:1373–1378

    Article  PubMed  CAS  Google Scholar 

  36. Cascinu S, Labianca R, Barone C et al (2007) Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. J Natl Cancer Inst 99:601–607

    Article  PubMed  CAS  Google Scholar 

  37. Smalley SR, Benedetti JK, Haller DG et al (2012) 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 30:2327–2333

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Park SH, Sohn TS, Lee J et al (2015) Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol 33:3130–3136

    Article  PubMed  CAS  Google Scholar 

  39. Smyth EC, Wotherspoon A, Peckitt C et al (2017) Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial. JAMA Oncol 3(9):1197–1203

    Article  PubMed  Google Scholar 

  40. Everett SM, Axon AT (1997) Early gastric cancer in Europe. Gut 41:142–150

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Fujitani K, Yang HK, Mizusawa J et al (2016) Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol 17(3):309–318

    Article  PubMed  CAS  Google Scholar 

  42. Al-Batran SE, Homann N, Pauligk C et al (2017) Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: the AIO-FLOT3 trial. JAMA Oncol 3(9):1237–1244

    Article  PubMed  PubMed Central  Google Scholar 

  43. Al-Batran SE, Goetze TO, Mueller DW et al (2017) The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction—a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer 17(1):893

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Stefan Paul Mönig.

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The article is part of the topical collection Gastric Cancer Surgery.

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Goetze, O.T., Al-Batran, SE., Chevallay, M. et al. Multimodal treatment in locally advanced gastric cancer. Updates Surg 70, 173–179 (2018). https://doi.org/10.1007/s13304-018-0539-z

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