Skip to main content

Induction Chemotherapy Plus Neoadjuvant Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma

Annals of Surgical Oncology volume 28, pages 7208–7218 (2021)Cite this article

Abstract

Background

Neoadjuvant chemotherapy with concurrent radiotherapy (nCRT) is an accepted treatment regimen for patients with potentially curable esophageal and gastroesophageal junction (GEJ) adenocarcinoma. The purpose of this study is to evaluate whether induction chemotherapy (IC) before nCRT is associated with improved pathologic complete response (pCR) and overall survival (OS) when compared with patients who received nCRT alone for esophageal and GEJ adenocarcinoma.

Methods

Using the National Cancer Database (NCDB), patients who received nCRT and curative-intent esophagectomy for esophageal or GEJ adenocarcinoma from 2006 to 2015 were included. Chemotherapy and radiation therapy start dates were used to define cohorts who received IC before nCRT (IC + nCRT) versus those who only received concurrent nCRT before surgery. Propensity weighting was conducted to balance patient, disease, and facility covariates between groups.

Results

12,460 patients met inclusion criteria, of whom 11,880 (95%) received nCRT and 580 (5%) received IC + nCRT. Following propensity weighting, OS was significantly improved among patients who received IC + nCRT versus nCRT (HR 0.82; 95% CI 0.74–0.92; p < 0.001) with median OS for the IC + nCRT cohort of 3.38 years versus 2.45 years for nCRT. For patients diagnosed from 2013 to 2015, IC + nCRT was also associated with higher odds of pCR compared with nCRT (OR 1.59; 95% CI 1.14–2.21; p = 0.007).

Conclusion

IC + nCRT was associated with a significant OS benefit as well as higher pCR rate in the more modern patient cohort. These results merit consideration of a sufficiently powered prospective multiinstitutional trial to further evaluate these observed differences.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends-an update. Cancer Epidemiol Biomarkers Prev. 2016;25(1):16–27.

    Article  Google Scholar 

  2. 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.

    Article  CAS  Google Scholar 

  3. Shapiro J, van Lanschot JJB, Hulshof M, 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):1090–8.

    Article  Google Scholar 

  4. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.

    Article  Google Scholar 

  5. Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26(7):1086–92.

    Article  CAS  Google Scholar 

  6. Ajani JA, D’Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17(7):855–83.

    Article  CAS  Google Scholar 

  7. Xi M, Liao Z, Deng W, et al. A Prognostic scoring model for the utility of induction chemotherapy prior to neoadjuvant chemoradiotherapy in esophageal cancer. J Thorac Oncol. 2017;12(6):1001–10.

    Article  Google Scholar 

  8. Jin J, Liao Z, Zhang Z, et al. Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys. 2004;60(2):427–36.

    Article  Google Scholar 

  9. Malaisrie SC, Hofstetter WL, Correa AM, et al. The addition of induction chemotherapy to preoperative, concurrent chemoradiotherapy improves tumor response in patients with esophageal adenocarcinoma. Cancer. 2006;107(5):967–74.

    Article  CAS  Google Scholar 

  10. Cercek A, Roxburgh CSD, Strombom P, et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4(6):e180071.

    Article  Google Scholar 

  11. Petrelli F, Trevisan F, Cabiddu M, et al. Total neoadjuvant therapy in rectal cancer: a systematic review and meta-analysis of treatment outcomes. Ann Surg. 2020;271(3):440–8.

    Article  Google Scholar 

  12. Goodman KA, Niedzwiecki D, Hall N, et al. Initial results of CALGB 80803 (Alliance): a randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer. J Clin Oncol. 2017;35(4_suppl):1.

    Article  Google Scholar 

  13. Goodman KA, Hall N, Bekaii-Saab TS, et al. Survival outcomes from CALGB 80803 (Alliance): a randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer. J Clin Oncol. 2018;36(15_suppl):4012–4012.

    Article  Google Scholar 

  14. Harada K, Wang X, Shimodaira Y, et al. Early metabolic change after induction chemotherapy predicts histologic response and prognosis in patients with esophageal cancer: secondary analysis of a randomized trial. Target Oncol. 2018;13(1):99–106.

    Article  Google Scholar 

  15. Ajani JA, Xiao L, Roth JA, et al. A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol. 2013;24(11):2844–9.

    Article  CAS  Google Scholar 

  16. Shimodaira Y, Slack RS, Harada K, et al. Influence of induction chemotherapy in trimodality therapy-eligible oesophageal cancer patients: secondary analysis of a randomised trial. Br J Cancer. 2018;118(3):331–7.

    Article  Google Scholar 

  17. National Cancer Database. [cited 2020 1/1/2020]; Available from: www.facs.org/quality-programs/cancer/ncdb.

  18. Mohanty S, Bilimoria KY. Comparing national cancer registries: The National Cancer Data Base (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) program. J Surg Oncol. 2014;109(7):629–30.

    Article  Google Scholar 

  19. Rosenbaum PR, Rubin DB. Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc. 1984;79(387):516–24.

    Article  Google Scholar 

  20. Rubin DB. Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1997;127(8 Pt 2):757–63.

    Article  CAS  Google Scholar 

  21. Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000;11(5):550–60.

    Article  CAS  Google Scholar 

  22. Herskovic A, Russell W, Liptay M, et al. Esophageal carcinoma advances in treatment results for locally advanced disease: review. Ann Oncol. 2012;23(5):1095–103.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

F.H. is supported by the Dr. Harold J. and Claire Wanebo Endowed Research Fellowship at University of Colorado. R.J.T is supported by NIH/NCATS Colorado CTSA grant no. TL1 TR002533. S.W. is supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Felix Ho MD, MPH, Robert J. Torphy MD, PhD, Chloe Friedman MPH, Ana L. Gleisner MD, PhD & Martin D. McCarter MD

  2. Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Stephen Leong MD & Sunnie Kim MD

  3. Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Sachin Wani MD

  4. Department of Radiation Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Tracey Schefter MD

  5. Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Christopher D. Scott MD, John D. Mitchell MD, Michael J. Weyant MD & Robert A. Meguid MD, MPH

  6. Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Karyn A. Goodman MD

Authors
  1. Felix Ho MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert J. Torphy MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chloe Friedman MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephen Leong MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sunnie Kim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sachin Wani MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tracey Schefter MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christopher D. Scott MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. John D. Mitchell MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael J. Weyant MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Robert A. Meguid MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ana L. Gleisner MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Karyn A. Goodman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Martin D. McCarter MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin D. McCarter MD.

Ethics declarations

Disclosure

S.W.: consultant for Boston Scientific, Medtronic, Interpace and Cernostics. M.W.: Intuitive Surgical-Educational Consultant; Medtronic-educational consultant. Other authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ho, F., Torphy, R.J., Friedman, C. et al. Induction Chemotherapy Plus Neoadjuvant Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma. Ann Surg Oncol 28, 7208–7218 (2021). https://doi.org/10.1245/s10434-021-09999-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-021-09999-5