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Impact of External-Beam Radiation Therapy on Outcomes Among Patients with Resected Gastric Cancer: A Multi-institutional Analysis

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Use of perioperative chemotherapy (CTx) alone versus chemoradiation therapy (cXRT) in the treatment of resectable gastric cancer remains varied. We sought to define the utilization and effect of CTx alone versus cXRT on patients having undergone curative-intent resection for gastric cancer.

Methods

Using the multi-institutional US Gastric Cancer Collaborative database, we identified 505 gastric cancer patients between 2000 and 2012 who received perioperative therapy in addition to curative-intent resection. The impact of perioperative therapy on survival was analyzed by the use of propensity-score matching of clinicopathologic factors among patients who received CTx alone versus cXRT.

Results

Median patient age was 62 years, and most patients were male (58.2 %). Most patients had a T3 (38.7 %) or T4 (36.8 %) lesion and lymph node metastasis (73.4 %). A total of 211 (42.8 %) patients received perioperative CTx alone, whereas the remaining 294 (58.2 %) patients received cXRT. Factors associated with receipt of cXRT were younger age (odds ratio, 1.93) and lymph node metastasis (odds ratio, 4.02; both P < 0.05). At a median follow-up of 28 months, the median overall survival (OS) was 33.4 months, and the 5-year OS was 36.7 %. Factors associated with worse overall survival included large tumor size [hazard ratio (HR), 1.83], T3 (HR 2.96) or T4 (HR 4.02) tumors, and lymph node metastasis (HR 1.57; all P < 0.05). In contrast, receipt of cXRT was associated with improved long-term OS (CTx alone, 20.9 months; cXRT, 46.7 months; HR 0.51; P < 0.001).

Conclusions

cXRT was utilized in 58 % of patients undergoing curative-intent resection for gastric cancer. With propensity score-matched analysis, cXRT was an independent factor associated with improved recurrence-free survival and OS.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol. 2013;107:230–6.

    Article  PubMed  Google Scholar 

  3. Arrington AK, Nelson R, Patel SS, et al. Timing of chemotherapy and survival in patients with resectable gastric adenocarcinoma. World J Gastrointest Surg. 2013;5:321–8.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Degiuli M, Sasako M, Ponti A, et al. Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer. Br J Surg. 2014;101:23–31.

    Article  PubMed  CAS  Google Scholar 

  5. Isozaki H, Okajima K, Fujii K, et al. Effectiveness of paraaortic lymph node dissection for advanced gastric cancer. Hepatogastroenterology. 1999;46:549–54.

    PubMed  CAS  Google Scholar 

  6. Berardi R, Scartozzi M, Romagnoli E, Antognoli S, Cascinu S. Gastric cancer treatment: a systematic review. Oncol Rep. 2004;11:911–6.

    PubMed  Google Scholar 

  7. Dickson JL, Cunningham D. Systemic treatment of gastric cancer. Eur J Gastroenterol Hepatol. 2004;16:255–63.

    Article  PubMed  CAS  Google Scholar 

  8. Hirota WK, Zuckerman MJ, Adler DG, et al. ASGE guideline: the role of endoscopy in the surveillance of premalignant conditions of the upper GI tract. Gastrointest Endosc. 2006;63:570–80.

    Article  PubMed  Google Scholar 

  9. Kim JP, Lee JH, Kim SJ, Yu HJ, Yang HK. Clinicopathologic characteristics and prognostic factors in 10 783 patients with gastric cancer. Gastric Cancer. 1998;1:125–33.

    Article  PubMed  Google Scholar 

  10. Janunger KG, Hafstrom L, Glimelius B. Chemotherapy in gastric cancer: a review and updated meta-analysis. Eur J Surg. 2002;168:597–608.

    Article  PubMed  CAS  Google Scholar 

  11. Mari E, Floriani I, Tinazzi A, et al. Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials. A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente). Ann Oncol. 2000;11:837–43.

    Article  PubMed  CAS  Google Scholar 

  12. Wanebo HJ, Kennedy BJ, Chmiel J, Steele G Jr, Winchester D, Osteen R. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. 1993;218:583–92.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Reid-Lombardo KM, Gay G, Patel-Parekh L, et al. Treatment of gastric adenocarcinoma may differ among hospital types in the United States, a report from the National Cancer Data Base. J Gastrointest Surg. 2007;11:410–9; discussion 9–20.

    Article  PubMed  PubMed Central  Google Scholar 

  14. D’Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004;240:808–16.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Coburn NG, Guller U, Baxter NN, et al. Adjuvant therapy for resected gastric cancer: rapid, yet incomplete adoption following results of intergroup 0116 trial. Int J Radiat Oncol Biol Phys. 2008;70:1073–80.

    Article  PubMed  Google Scholar 

  16. 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;345:725–30.

    Article  PubMed  CAS  Google Scholar 

  17. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.

    Article  PubMed  CAS  Google Scholar 

  18. Hyder O, Dodson RM, Sachs T, et al. Impact of adjuvant external beam radiotherapy on survival in surgically resected gallbladder adenocarcinoma: a propensity score-matched Surveillance, Epidemiology, and End Results analysis. Surgery. 2014;155:85–94.

    Article  PubMed  Google Scholar 

  19. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med. 1997;336:980–7.

  20. Liao Z, Zhang Z, Jin J, et al. Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients. Int J Radiat Oncol Biol Phys. 2004;60:1484–93.

    Article  PubMed  Google Scholar 

  21. Moertel CG, Childs DS Jr, Reitemeier RJ, Colby MY Jr, Holbrook MA. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969;2:865–7.

    Article  PubMed  CAS  Google Scholar 

  22. Skoropad V, Berdov B, Zagrebin V. Concentrated preoperative radiotherapy for resectable gastric cancer: 20-years follow-up of a randomized trial. J Surg Oncol. 2002;80:72–8.

    Article  PubMed  Google Scholar 

  23. Takahashi M, Abe M. Intra-operative radiotherapy for carcinoma of the stomach. Eur J Surg Oncol. 1986;12:247–50.

    PubMed  CAS  Google Scholar 

  24. Allum WH, Hallissey MT, Ward LC, Hockey MS. A controlled, prospective, randomised trial of adjuvant chemotherapy or radiotherapy in resectable gastric cancer: interim report. British Stomach Cancer Group. Br J Cancer. 1989;60:739–44.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Zhang ZX, Gu XZ, Yin WB, Huang GJ, Zhang DW, Zhang RG. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC): report on 370 patients. Int J Radiat Oncol Biol Phys. 1998;42:929–34.

    Article  PubMed  CAS  Google Scholar 

  26. Glynn RJ, Schneeweiss S, Sturmer T. Indications for propensity scores and review of their use in pharmacoepidemiology. Basic Clinic Pharmacol Toxicol. 2006;98:253–9.

    Article  CAS  Google Scholar 

  27. Rassen JA, Shelat AA, Myers J, Glynn RJ, Rothman KJ, Schneeweiss S. One-to-many propensity score matching in cohort studies. Pharmacoepidemiol Drug Saf. 2012;21(Suppl. 2):69–80.

    Article  PubMed  Google Scholar 

  28. Koppert LB, Lemmens VE, Coebergh JW, et al. Impact of age and co-morbidity on surgical resection rate and survival in patients with oesophageal and gastric cancer. Br J Surg. 2012;99:1693–700.

    Article  PubMed  CAS  Google Scholar 

  29. Bickenbach KA, Gonen M, Strong V, Brennan MF, Coit DG. Association of positive transection margins with gastric cancer survival and local recurrence. Ann Surg Oncol. 2013;20:2663–8.

    Article  PubMed  CAS  Google Scholar 

  30. Lee SE, Ryu KW, Nam BH, et al. Prognostic significance of intraoperatively estimated surgical stage in curatively resected gastric cancer patients. J Am Coll Surg. 2009;209:461–7.

    Article  PubMed  Google Scholar 

  31. Deng J, Liang H, Wang D, Sun D, Pan Y, Liu Y. Investigation of the recurrence patterns of gastric cancer following a curative resection. Surg Today. 2011;41:210–5.

    Article  PubMed  Google Scholar 

  32. Wu CW, Lo SS, Shen KH, et al. Incidence and factors associated with recurrence patterns after intended curative surgery for gastric cancer. World J Surg. 2003;27:153–8.

    PubMed  Google Scholar 

  33. Huang KH, Chen JH, Wu CW, et al. Factors affecting recurrence in node-negative advanced gastric cancer. J Gastroenterol Hepatol. 2009;24:1522–6.

    Article  PubMed  Google Scholar 

  34. Sakar B, Karagol H, Gumus M, et al. Timing of death from tumor recurrence after curative gastrectomy for gastric cancer. Am J Clin Oncol. 2004;27:205–9.

    Article  PubMed  Google Scholar 

  35. Mayo SC, de Jong MC, Bloomston M, et al. Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: a multicenter international analysis. Ann Surg Oncol. 2011;18:3657–65.

    Article  PubMed  Google Scholar 

  36. Gleisner AL, Choti MA, Assumpcao L, Nathan H, Schulick RD, Pawlik TM. Colorectal liver metastases: recurrence and survival following hepatic resection, radiofrequency ablation, and combined resection-radiofrequency ablation. Arch Surg. 2008;143:1204–12.

    Article  PubMed  Google Scholar 

  37. Ohri N, Garg MK, Aparo S, et al. Who benefits from adjuvant radiation therapy for gastric cancer? A meta-analysis. Int J Radiat Oncol Biol Phys. 2013;86:330–5.

    Article  PubMed  Google Scholar 

  38. 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;30:2327–33.

    Article  PubMed  CAS  Google Scholar 

  39. Dent DM, Werner ID, Novis B, Cheverton P, Brice P. Prospective randomized trial of combined oncological therapy for gastric carcinoma. Cancer. 1979;44:385–91.

    Article  PubMed  CAS  Google Scholar 

  40. A comparison of combination chemotherapy and combined modality therapy for locally advanced gastric carcinoma. Gastrointestinal Tumor Study Group. Cancer. 1982;49:1771–7.

  41. Moertel CG, Childs DS, O’Fallon JR, Holbrook MA, Schutt AJ, Reitemeier RJ. Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma. J Clin Oncol. 1984;2:1249–54.

    PubMed  CAS  Google Scholar 

  42. The concept of locally advanced gastric cancer. Effect of treatment on outcome. The Gastrointestinal Tumor Study Group. Cancer. 1990;66:2324–30.

  43. Jacome AA, Wohnrath DR, Scapulatempo Neto C, et al. Effect of adjuvant chemoradiotherapy on overall survival of gastric cancer patients submitted to D2 lymphadenectomy. Gastric Cancer. 2013;16:233–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  44. Fiorica F, Cartei F, Enea M, et al. The impact of radiotherapy on survival in resectable gastric carcinoma: a meta-analysis of literature data. Cancer Treat Rev. 2007;33:729–40.

    Article  PubMed  Google Scholar 

  45. Bamias A, Karina M, Papakostas P, et al. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010;65:1009–21.

    Article  PubMed  CAS  Google Scholar 

  46. Douglass HO Jr, Stablein DM, Thomas PR. An organized multi-institutional interdisciplinary evaluation of role of radiation therapy alone or combined with chemotherapy in treatment of adenocarcinoma of the gastrointestinal tract. NCI Monogr. 1988;(6):253–7.

    PubMed  Google Scholar 

  47. Xiong HQ, Gunderson LL, Yao J, Ajani JA. Chemoradiation for resectable gastric cancer. Lancet Oncol. 2003;4:498–505.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

Dr. Ejaz was supported in part by the Eleanor B. Pillsbury Foundation for surgical research.

Disclosure

Aslam Ejaz, Gaya Spolverato, Yuhree Kim, Malcolm H. Squires, George Poultsides, Ryan Fields, Mark Bloomston, Sharon M. Weber, Konstantinos Votanopoulos, David J. Worhunsky, Douglas Swords, Linda X. Jin, Carl Schmidt, Alexandra W. Acher, Neil Saunders, Clifford S. Cho, Joseph M. Herman, Shishir K. Maithel, Timothy M. Pawlik, Aslam Ejaz, Gaya Spolverato, Yuhree Kim, Malcolm H. Squires, George Poultsides, Ryan Fields, Mark Bloomston, Sharon M. Weber, Konstantinos Votanopoulos, David J. Worhunsky, Douglas Swords, Linda X. Jin, Carl Schmidt, Alexandra W. Acher, Neil Saunders, Clifford S. Cho, Joseph M. Herman, Shishir K. Maithel, Timothy M. Pawlik has nothing to disclose.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, John L. Cameron Professor of Alimentary Surgery, Johns Hopkins Hospital, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Aslam Ejaz MD, Gaya Spolverato MD, Yuhree Kim MD, MPH, Joseph M. Herman MD & Timothy M. Pawlik MD, MPH, PhD, FACS

  2. Department of Surgery, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA

    Aslam Ejaz MD

  3. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Malcolm H. Squires MD & Shishir K. Maithel MD

  4. Department of Surgery, Stanford University, Palo Alto, CA, USA

    George Poultsides MD & David J. Worhunsky MD

  5. Department of Surgery, Washington University, St. Louis, MO, USA

    Ryan Fields MD & Linda X. Jin MD

  6. Department of Surgery, The Ohio State University, Columbus, OH, USA

    Mark Bloomston MD, Carl Schmidt MD & Neil Saunders MD

  7. Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA

    Sharon M. Weber MD, Alexandra W. Acher MD & Clifford S. Cho MD

  8. Department of Surgery, Wake Forest University, Winston-Salem, NC, USA

    Konstantinos Votanopoulos MD & Douglas Swords MD

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  1. Aslam Ejaz MD
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  18. Shishir K. Maithel MD
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  19. Timothy M. Pawlik MD, MPH, PhD, FACS
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Corresponding author

Correspondence to Timothy M. Pawlik MD, MPH, PhD, FACS.

Additional information

A video of the presentation of the data in this article at the 67th Annual Society of Surgical Oncology Cancer Symposium is available at http://www.surgonc.org/vm.

Electronic supplementary material

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10434_2014_3776_MOESM1_ESM.eps

A Overall survival in the propensity score–matched cohort among patients who received chemoradiation (cXRT) versus chemotherapy alone (CTx) (EPS 372 kb)

10434_2014_3776_MOESM2_ESM.eps

B Recurrence-free survival in the propensity score–matched cohort among patients who received chemoradiation (cXRT) versus chemotherapy alone (CTx) (EPS 376 kb)

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Ejaz, A., Spolverato, G., Kim, Y. et al. Impact of External-Beam Radiation Therapy on Outcomes Among Patients with Resected Gastric Cancer: A Multi-institutional Analysis. Ann Surg Oncol 21, 3412–3421 (2014). https://doi.org/10.1245/s10434-014-3776-5

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