Annals of Surgical Oncology

, Volume 20, Issue 6, pp 1985–1992 | Cite as

Survival after Definitive (Chemo)Radiotherapy in Esophageal Cancer Patients: A Population-Based Study in the North-East Netherlands

  • Justin K. Smit
  • Christina T. Muijs
  • Johannes G. M. Burgerhof
  • Gabriel Paardekooper
  • Paul R. Timmer
  • Karin Muller
  • Dankert Woutersen
  • Véronique E. Mul
  • Jannet C. Beukema
  • Geke A. P. Hospers
  • Boukje A. C. van Dijk
  • Johannes A. Langendijk
  • John Th. M. Plukker
Gastrointestinal Oncology



Definitive (chemo)radiotherapy is employed in esophageal cancer patients as an alternative for patients considered medically unfit for surgery or having unresectable tumors. We evaluated a population-based cohort to improve the selection for intensified nonsurgical strategies and to identify prognostic factors.


Patients who had squamous cell carcinoma (SCC) or adenocarcinoma (AC) were treated in four referral centers in the north-east Netherlands with definitive chemoradiotherapy (dCRT) or radiotherapy (dRT) between 1996 and 2008.


Of the 287 included patients, 110 were treated with dCRT and 177 with dRT. Median overall survival (OS) was 11 months (95 % confidence interval: 10–12 months), with OS of 22 and 8 % and disease-free survival (DFS) of 16 and 5 % at 2 and 5 years, respectively. DFS at 2 and 5 years was 24 and 9 % for SCC versus 10 and 2 % for AC patients (P = 0.006). OS after 2 and 5 years was 29 and 14 % for SCC patients versus 17 and 3 % for AC patients (P = 0.044). On multivariate Cox regression, SCC was an independent prognostic factor for DFS [P = 0.020, hazard ratio (HR) = 0.71] and OS (P = 0.047, HR = 0.76). On matched cohort analysis, DFS was higher in the dCRT group compared with dRT patients (P = 0.016). The locoregional failure rate was lower in the dCRT group and in SCC patients (P = 0.001 and 0.046).


Long-term results and the local control rate in SCC patients were better after definitive (chemo)radiotherapy compared with in AC patients. SCC was an independent prognostic factor for survival. Definitive chemoradiotherapy leads to improved local control rate and DFS.


Overall Survival Squamous Cell Carcinoma Gross Tumor Volume Radiation Therapy Oncology Group Squamous Cell Carcinoma Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by GUIDE Post-graduate School of Medicine, University of Groningen. The authors would like to thank Michael G. Dickinson MD for editing our manuscript.


  1. 1.
    Brown LM, Devesa SS, Chow WH. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst. 2008;100:1184–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Crane LM, Schaapveld M, Visser O, Louwman MW, Plukker JT, van Dam GM. Oesophageal cancer in The Netherlands: increasing incidence and mortality but improving survival. Eur J Cancer. 2007;43:1445–51.PubMedCrossRefGoogle Scholar
  3. 3.
    IKN. Available: Accessed 1 March 2012.
  4. 4.
    Smith GL, Smith BD, Buchholz TA, Liao Z, Jeter M, Swisher SG, et al. Patterns of care and locoregional treatment outcomes in older esophageal cancer patients: The SEER-Medicare Cohort. Int J Radiat Oncol Biol Phys. 2009;74:482–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Mariette C, Piessen G, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol. 2007;8:545–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Omloo JM, Lagarde SM, Hulscher JB, Reitsma JB, Fockens P, van Dekken H, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg. 2007;246:992–1000; discussion 1000–1.PubMedCrossRefGoogle Scholar
  7. 7.
    Smit JK, Pultrum BB, van Dullemen HM, Van Dam GM, Groen H, Plukker JT. Prognostic factors and patterns of recurrence in esophageal cancer assert arguments for extended two-field transthoracic esophagectomy. Am J Surg. 2010;200:446–53.Google Scholar
  8. 8.
    Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8:226–34.PubMedCrossRefGoogle Scholar
  9. 9.
    Kaklamanos IG, Walker GR, Ferry K, Franceschi D, Livingstone AS. Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol. 2003;10:754–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.PubMedCrossRefGoogle Scholar
  11. 11.
    Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999;281:1623–7.Google Scholar
  12. 12.
    Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326:1593–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Muijs CT, Beukema JC, Mul VE, Plukker JT, Sijtsema NM, Langendijk JA. External beam radiotherapy combined with intraluminal brachytherapy in esophageal carcinoma. Radiother Oncol. 2011;102(2):303–8.Google Scholar
  14. 14.
    Smith TJ, Ryan LM, Douglass HO Jr, Haller DG, Dayal Y, Kirkwood J, et al. Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys. 1998;42:269–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Geh JI, Bond SJ, Bentzen SM, Glynne-Jones R. Systematic overview of preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer: evidence of a radiation and chemotherapy dose response. Radiother Oncol. 2006;78:236–44.PubMedCrossRefGoogle Scholar
  16. 16.
    Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005;23:2310–17.PubMedCrossRefGoogle Scholar
  17. 17.
    Bedenne L, Michel P, Bouche O, Milan C, Mariette C, Conroy T, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007;25:1160–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Gaspar LE, Winter K, Kocha WI, Coia LR, Herskovic A, Graham M. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group study 9207): final report. Cancer. 2000;88:988–95.PubMedCrossRefGoogle Scholar
  19. 19.
    Sobin LH. TNM, sixth edition: new developments in general concepts and rules. Semin Surg Oncol. 2003;21:19–22.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang H, Ryu J, Gandara D, Bold RJ, Urayama S, Tanaka M, et al. A phase II study of paclitaxel, carboplatin, and radiation with or without surgery for esophageal cancer. J Thorac Oncol. 2007;2:153–7.PubMedCrossRefGoogle Scholar
  21. 21.
    D’Agostino RB,Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.PubMedCrossRefGoogle Scholar
  22. 22.
    Weitzen S, Lapane KL, Toledano AY, Hume AL, Mor V. Principles for modeling propensity scores in medical research: a systematic literature review. Pharmacoepidemiol Drug Saf. 2004;13:841–53.PubMedCrossRefGoogle Scholar
  23. 23.
    Sykes AJ, Burt PA, Slevin NJ, Stout R, Marrs JE. Radical radiotherapy for carcinoma of the oesophagus: an effective alternative to surgery. Radiother Oncol. 1998;48:15–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, et al. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005;6:659–68.PubMedCrossRefGoogle Scholar
  25. 25.
    Gaast AV, van Hagen P, Hulshof M, Richel D, van Berge Henegouwen MI, Nieuwenhuijzen GA, et al. Effect of preoperative concurrent chemoradiotherapy on survival of patients with resectable esophageal or esophagogastric junction cancer: results from a multicenter randomized phase III study. J Clin Oncol. 2010;(suppl; abstr 4004): 28:15.CrossRefGoogle Scholar
  26. 26.
    Fiorica F, Di Bona D, Schepis F, Licata A, Shahied L, Venturi A, et al. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53:925–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Lee PC, Mirza FM, Port JL, Stiles BM, Paul S, Christos P, Altorki NK. Predictors of recurrence and disease-free survival in patients with completely resected esophageal carcinoma. J Thorac Cardiovasc Surg. 2011;141:1196–206.PubMedCrossRefGoogle Scholar
  28. 28.
    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;355:11–20.PubMedCrossRefGoogle Scholar
  29. 29.
    Ychou M, Boige V, Pignon JP, Conroy T, Bouché 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;29:1715–21.PubMedCrossRefGoogle Scholar
  30. 30.
    Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20:1167–74.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Justin K. Smit
    • 1
  • Christina T. Muijs
    • 2
  • Johannes G. M. Burgerhof
    • 3
  • Gabriel Paardekooper
    • 4
  • Paul R. Timmer
    • 4
  • Karin Muller
    • 5
  • Dankert Woutersen
    • 6
  • Véronique E. Mul
    • 2
  • Jannet C. Beukema
    • 2
  • Geke A. P. Hospers
    • 7
  • Boukje A. C. van Dijk
    • 8
  • Johannes A. Langendijk
    • 2
  • John Th. M. Plukker
    • 1
  1. 1.Surgical Oncology of the University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  2. 2.Radiation Oncology of the University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  3. 3.Epidemiology of the University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  4. 4.Radiation OncologyIsala KliniekenZwolleThe Netherlands
  5. 5.Radiotherapy Institute Stedendriehoek en OmstrekenDeventerThe Netherlands
  6. 6.Medisch Spectrum TwenteEnschedeThe Netherlands
  7. 7.Medical Oncology of the University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  8. 8.Section of EpidemiologyComprehensive Cancer CentersUtrechtThe Netherlands

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