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Annals of Surgical Oncology

, Volume 26, Issue 11, pp 3618–3626 | Cite as

Impact of ypT, ypN, and Adjuvant Therapy on Survival in Gastric Cancer Patients Treated with Perioperative Chemotherapy and Radical Surgery

  • Felipe José Fernández CoimbraEmail author
  • Victor Hugo F. de Jesus
  • Héber S. C. Ribeiro
  • Alessandro L. Diniz
  • André Luís de Godoy
  • Igor Correia de Farias
  • Tiago Felismino
  • Celso A. L. Mello
  • Maria Fernanda Almeida
  • Maria Dirlei F. S. Begnami
  • Emmanuel Dias-Neto
  • Rachel S. P. Riechelmann
  • Wilson L. da CostaJr.Email author
Gastrointestinal Oncology
  • 146 Downloads

Abstract

Background

Perioperative chemotherapy and surgery is the standard of care in advanced gastroesophageal cancer patients, but its impact among those treated with radical surgery still needs further assessment. We present the results of this multimodality treatment approach in a gastric cancer patients cohort treated with D2 lymphadenectomy. We aimed to identify prognostic factors associated with improved survival.

Patients and Methods

This retrospective cohort study enrolled patients treated with perioperative chemotherapy and resection in a single cancer center in Brazil between 2006 and 2016. Subjects presenting tumors of the gastric stump, esophageal tumors, or treated with intraperitoneal chemotherapy were excluded. Intention-to-treat survival analysis was performed for all subjects who started neoadjuvant chemotherapy, and prognostic factors were determined among those who had R0 resection.

Results

This study included 239 patients, of whom 198 had R0 resection. The mean age was 59.9 years, and most had clinical stage IIB or III disease (88%). Among the 239 patients who started neoadjuvant chemotherapy, 207 (86.6%) completed all neoadjuvant treatment cycles, and surgical resection was performed in 225 subjects (94.1%). Overall 60-day morbidity and mortality rates were 35.6% and 4.4%, respectively. For the entire cohort, median survival was 78 months and the 5-year survival rate was 55.3%. Factors associated with worse survival were ypT3–4 stage, ypN + stage, extended resection, and no adjuvant chemotherapy.

Conclusions

Perioperative chemotherapy resulted in very good outcomes for patients treated with radical surgery, and downstaging after chemotherapy was shown to be a major determinant of prognosis.

Notes

Acknowledgment

The authors acknowledge the financial support given by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Project 2014/26897-0.

Disclosures

All the authors in this study report no disclosures.

References

  1. 1.
    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):11–20.CrossRefGoogle Scholar
  2. 2.
    Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, 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):1715–21.CrossRefGoogle Scholar
  3. 3.
    Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28(35):5210–8.CrossRefGoogle Scholar
  4. 4.
    Schmidt T, Sicic L, Blank S, Becker K, Weichert W, Bruckner T, et al. Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas. Br J Cancer. 2014;110(7):1712–20.CrossRefGoogle Scholar
  5. 5.
    Becker K, Langer R, Reim D, Novotny A, Meyer zum Buschenfelde C, Engel J, et al. Significance of histopathological tumor regression after neoadjuvant chemotherapy in gastric adenocarcinomas: a summary of 480 cases. Ann Surg. 2011;253(5):934–9.CrossRefGoogle Scholar
  6. 6.
    Reddavid R, Sofia S, Chiaro P, Colli F, Trapani R, Esposito L, et al. Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake? World J Gastroenterol. 2018;24(2):274–89.CrossRefGoogle Scholar
  7. 7.
    Ahn HS, Lee HJ, Yoo MW, Kim SG, Im JP, Kim SH, et al. Diagnostic accuracy of T and N stages with endoscopy, stomach protocol CT, and endoscopic ultrasonography in early gastric cancer. J Surg Oncol. 2009;99(1):20–7.CrossRefGoogle Scholar
  8. 8.
    Almeida MFA, Verza L, Bitencourt AGV, Boaventura CS, Barbosa P, Chojniak R. Computed tomography with a stomach protocol and virtual gastroscopy in the staging of gastric cancer: an initial experience. Radiol Bras. 2018;51(4):211–7.CrossRefGoogle Scholar
  9. 9.
    Zhong X, Lim EA, Hershman DL, Moinpour CM, Unger J, Lee SM. Identifying severe adverse event clusters using the National Cancer Institute’s common terminology criteria for adverse events. J Oncol Pract. 2016;12(3):e270–80, 45–46.Google Scholar
  10. 10.
    Doyle DJ, Garmon EH. American Society of Anesthesiologists Classification (ASA Class). Treasure Island: StatPearls; 2018.Google Scholar
  11. 11.
    Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20(1):1–19.CrossRefGoogle Scholar
  12. 12.
    Brierley J, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 8th edn. Hoboken: Wiley; 2017.Google Scholar
  13. 13.
    Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, 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):616–28.CrossRefGoogle Scholar
  14. 14.
    Al-Batran S-E, Hofheinz RD, Pauligk C, Kopp H-G, 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):1697–708.CrossRefGoogle Scholar
  15. 15.
    Ikoma N, Hofstetter WL, Estrella JS, Das P, Minsky BD, Fournier KF, et al. The ypT category does not impact overall survival in node negative gastric cancer. J Surg Oncol. 2018;117(8):1721–8.CrossRefGoogle Scholar
  16. 16.
    Claassen YHM, van Amelsfoort RM, Hartgrink HH, Dikken JL, de Steur WO, van Sandick JW, et al. Effect of hospital volume with respect to performing gastric cancer resection on recurrence and survival: results from the CRITICS trial. Ann Surg. 2018.  https://doi.org/10.1097/sla.0000000000002940.Google Scholar
  17. 17.
    Degiuli M, Sasako M, Ponti A, Vendrame A, Tomatis M, Mazza C, et al. Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer. Br J Surg. 2014;101(2):23–31.CrossRefGoogle Scholar
  18. 18.
    Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, 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):4387–93.CrossRefGoogle Scholar
  19. 19.
    Bashash M, Hislop TG, Shah AM, Le N, Brooks-Wilson A, Bajdik CD. The prognostic effect of ethnicity for gastric and esophageal cancer: the population-based experience in British Columbia, Canada. BMC Cancer. 2011;11:164.CrossRefGoogle Scholar
  20. 20.
    Ma Y, Tang L, Wang HX, Xu YC, Ma Y, Zhang FC. Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and ethnicity. J Clin Pharm Ther. 2012;37(3):266–75.CrossRefGoogle Scholar
  21. 21.
    Mansour JC, Tang L, Shah M, Bentrem D, Klimstra DS, Gonen M, et al. Does graded histologic response after neoadjuvant chemotherapy predict survival for completely resected gastric cancer? Ann Surg Oncol. 2007;14(12):3412–8.CrossRefGoogle Scholar
  22. 22.
    Noble F, Lloyd MA, Turkington R, Griffiths E, O’Donovan M, O’Neill JR, et al. Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma. Br J Surg. 2017;104(13):1816–28.CrossRefGoogle Scholar
  23. 23.
    Davies AR, Gossage JA, Zylstra J, Mattsson F, Lagergren J, Maisey N, et al. Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol. 2014;32(27):2983–90.CrossRefGoogle Scholar
  24. 24.
    da Costa WL Jr, Coimbra FJ, Ribeiro HS, Diniz AL, de Godoy AL, de Farias IC, et al. Total gastrectomy for gastric cancer: an analysis of postoperative and long-term outcomes through time: results of 413 consecutive cases in a single cancer center. Ann Surg Oncol. 2015;22(3):750–7.CrossRefGoogle Scholar
  25. 25.
    Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet (Lond Engl). 2012;379(9813):315–21.CrossRefGoogle Scholar
  26. 26.
    Eto K, Hiki N, Kumagai K, Shoji Y, Tsuda Y, Kano Y, et al. Prophylactic effect of neoadjuvant chemotherapy in gastric cancer patients with postoperative complications. Gastric Cancer. 2018;21(4):703–9.CrossRefGoogle Scholar
  27. 27.
    Lorenzen S, Blank S, Lordick F, Siewert JR, Ott K. Prediction of response and prognosis by a score including only pretherapeutic parameters in 410 neoadjuvant treated gastric cancer patients. Ann Surg Oncol. 2012;19(7):2119–27.CrossRefGoogle Scholar
  28. 28.
    Karagkounis G, Squires MH III, Melis M, Poultsides GA, Worhunsky D, Jin LX, et al. Predictors and prognostic implications of perioperative chemotherapy completion in gastric cancer. J Gastrointest Surg. 2017;21(12):1984–92.CrossRefGoogle Scholar
  29. 29.
    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):821–9.CrossRefGoogle Scholar
  30. 30.
    Feng XY, Wang W, Luo GY, Wu J, Zhou ZW, Li W, et al. Comparison of endoscopic ultrasonography and multislice spiral computed tomography for the preoperative staging of gastric cancer—results of a single institution study of 610 Chinese patients. PLoS ONE. 2013;8(11):e78846.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Felipe José Fernández Coimbra
    • 1
    Email author
  • Victor Hugo F. de Jesus
    • 2
  • Héber S. C. Ribeiro
    • 1
  • Alessandro L. Diniz
    • 1
  • André Luís de Godoy
    • 1
  • Igor Correia de Farias
    • 1
  • Tiago Felismino
    • 2
  • Celso A. L. Mello
    • 2
  • Maria Fernanda Almeida
    • 3
  • Maria Dirlei F. S. Begnami
    • 4
  • Emmanuel Dias-Neto
    • 5
  • Rachel S. P. Riechelmann
    • 2
  • Wilson L. da CostaJr.
    • 1
    Email author
  1. 1.Department of Abdominal SurgeryA. C. Camargo Cancer CenterSao PauloBrazil
  2. 2.Department of Clinical OncologyA. C. Camargo Cancer CenterSão PauloBrazil
  3. 3.Department of RadiologyA. C. Camargo Cancer CenterSão PauloBrazil
  4. 4.Department of Surgical PathologyHospital Sírio-LibanêsSão PauloBrazil
  5. 5.Laboratory of Medical GenomicsA. C. Camargo Cancer CenterSão PauloBrazil

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