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Impact of Chemoradiation-to-Surgery Interval on Pathological Complete Response and Short- and Long-Term Overall Survival in Esophageal Cancer Patients

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

Abstract

Background

The impact of the neoadjuvant chemoradiation-to-surgery (CRT-S) interval in patients with esophageal cancer is not clear. We aimed to determine the relationship between CRT-S interval and pathological complete response rate (pCR) and overall survival (OS).

Methods

National Cancer Data Base patients with CRT followed by surgery were studied. CRT-S interval was studied as a continuous (weeks) and categorical variable (quintiles: 15–37, 38–45, 46–53, 54–64, and 65–90 days, with n = 1016, 1063, 1081, 1083, and 938 patients, respectively).

Results

A total of 5181 patients were included; 81% had adenocarcinoma. There was a significant increase of pCR rate across quintiles (18%, 21%, 24%, 25%, and 29%, p < 0.001) and per week increase of CRT-S interval [odds ratio (OR) 1.11, p < 0.001]. The 90-day mortality increased as CRT-S increased across quintiles (5.7%, 6.2%, 6.8%, 8.5%, and 8.2%, p = 0.02) and through weeks (OR 1.05, p = 0.03). Mean OS across CRT-S quintiles was 36.4, 35.1, 33.9, 33.2, and 30.7 months, respectively. Multivariate Cox regression showed significantly worse OS per week increase in CRT-S interval [hazard ratio (HR) 1.02, p = 0.02], especially among the last quintile (CRT-S = 65–90 days: HR 1.2, p = 0.009). The squamous cell carcinoma (SCC) and pCR groups had similar OS across CTR-S intervals.

Conclusions

Despite the higher pCR rate with longer CRT-S interval, surgery is optimal less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. In patients with SCC and those with pCR, prolonged CRT-S interval had no impact on OS. Further studies are needed to consolidate our findings.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  2. Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. 1998;83:2049–53.

    Article  CAS  PubMed  Google Scholar 

  3. 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  PubMed  Google Scholar 

  4. Walsh TN, Grennell M, Mansoor S, Kelly A. Neoadjuvant treatment of advanced stage esophageal adenocarcinoma increases survival. Dis Esophagus. 2002;15(2):121–24.

    Article  CAS  PubMed  Google Scholar 

  5. Shapiro J, van Lanschot JJB, Hulshof MCCM, 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  PubMed  Google Scholar 

  6. 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  PubMed  Google Scholar 

  7. Malthaner R, Fenlon D. Preoperative chemotherapy for resectable thoracic esophageal cancer. Cochrane Database Syst Rev. 2006;3:CD001556.

    Google Scholar 

  8. Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19(2):305–13.

    Article  CAS  PubMed  Google Scholar 

  9. Mariette C, Dahan L, Mornex F, et al. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014;32(23):2416–22.

    Article  CAS  PubMed  Google Scholar 

  10. Haisley KR, Laird AE, Nabavizadeh N, et al. Association of intervals between neoadjuvant chemoradiation and surgical resection with pathologic complete response and survival in patients with esophageal cancer. JAMA Surg. 2016;151(11):e162743. https://doi.org/10.1001/jamasurg.2016.2743.

    Article  PubMed  Google Scholar 

  11. Shaikh T, Ruth K, Scott WJ, et al. Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer. Ann Thorac Surg. 2015;99(1):270–6.

    Article  PubMed  Google Scholar 

  12. Tsang JS, Tong DKH, Lam KO, et al. Appropriate timing for surgery after neoadjuvant chemoradiation for esophageal cancer. Dis Esophagus. 2017;30(9):1–8.

    Article  CAS  PubMed  Google Scholar 

  13. Franko J, Voynov G, Goldman CD. Esophagectomy timing after neoadjuvant therapy for distal esophageal adenocarcinoma. Ann Thorac Surg. 2016;101(3):1123–30.

    Article  PubMed  Google Scholar 

  14. Bilimoria KY, Stewart AK, Winchester DP, et al. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15(3):683–90.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Quan H, Li B, Couris CM, et al. Updating and validating the Charlson Comorbidity Index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676–82.

    Article  PubMed  Google Scholar 

  16. Shapiro J, van Hagen P, Lingsma HF, et al., CROSS Study Group. Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg. 2014;260(5):807–13.

    Article  PubMed  Google Scholar 

  17. Chiu CH, Chao YK, Chang HK, et al. Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma: does delayed surgery impact outcome? Ann Surg Oncol. 2013;20(13):4245–51.

    Article  PubMed  Google Scholar 

  18. Tessier W, Gronnier C, Messager M, et al. Does timing of surgical procedure after neoadjuvant chemoradiation affect outcomes in esophageal cancer? Ann Thorac Surg. 2014; 97(4):1181–9.

    Article  PubMed  Google Scholar 

  19. Kim JY, Correa AM, Vaporciyan AA, et al. Does the timing of esophagectomy after chemoradiation affect outcome? Ann Thorac Surg. 2012; 93(1):207–12 (discussion 212–3).

    Article  PubMed  Google Scholar 

  20. McCoy MJ, Lake RA, van der Most RG, Dick IM, Nowak AK. Post-chemotherapy T-cell recovery is a marker of improved survival in patients with advanced thoracic malignancies. Br J Cancer. 2012;107(7):1107–115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Westerterp M, Boermeester MA, Omloo JM, et al. Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus. Cancer Immunol Immunother. 2008;57(12):1837–47.

    Article  CAS  PubMed  Google Scholar 

  22. Zitvogel L, Kepp O, Senovilla L, Menger L, Chaput N, Kroemer G. Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin Cancer Res. 2010;16(12):3100–4.

    Article  CAS  PubMed  Google Scholar 

  23. Garg AD, Romano E, Rufo N, Agostinis P. Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation. Cell Death Differ. 2016;23(6):938–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jia D, Li L, Andrew S, et al. An autocrine inflammatory forward-feedback loop after chemotherapy withdrawal facilitates the repopulation of drug-resistant breast cancer cells. Cell Death Dis. 2017;8(7):e2932. https://doi.org/10.1038/cddis.2017.319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang BY, Chen HS, Hsu PK, et al. Clinical impact of the interval between chemoradiotherapy and esophagectomy in esophageal squamous cell carcinoma patients. Ann Thorac Surg. 2015;99(3):947–55.

    Article  PubMed  Google Scholar 

  26. Ranney DN, Mulvihill MS, Yerokun BA, et al. Surgical resection after neoadjuvant chemoradiation for oesophageal adenocarcinoma: what is the optimal timing? Eur J Cardiothorac Surg. 2017;52(3):543–51.

    Article  PubMed  Google Scholar 

  27. Kathiravetpillai N, Koeter M, van der Sangen MJ, et al. Delaying surgery after neoadjuvant chemoradiotherapy does not significantly influence postoperative morbidity or oncological outcome in patients with oesophageal adenocarcinoma. Eur J Surg Oncol. 2016;42(8):1183–90.

    Article  CAS  PubMed  Google Scholar 

  28. Ruol A, Rizzetto C, Castoro C, et al. Interval between neoadjuvant chemoradiotherapy and surgery for squamous cell carcinoma of the thoracic esophagus: does delayed surgery have an impact on outcome? Ann Surg. 2010;252(5):788–95.

    Article  PubMed  Google Scholar 

  29. Liu SL, Xi M, Yang H, et al. Is there a correlation between clinical complete response and pathological complete response after neoadjuvant chemoradiation for esophageal squamous cell cancer? Ann Surg Oncol. 2016;23(1):273–81.

    Article  PubMed  Google Scholar 

  30. Hamai Y, Hihara J, Emi M, et al. Esophagus: preoperative prediction of a pathologic complete response of esophageal squamous cell carcinoma to neoadjuvant chemoradiotherapy. Surgery. 2018;164(1):40–8.

    Article  Google Scholar 

  31. Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633–40.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Surgical Oncology, Sentara Healthcare, Newport News, VA, USA

    Basem Azab MD

  2. Division of Surgical Oncology, Dewitt-Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

    Julia R. Amundson MD, Omar Picado MD, Caroline Ripat MD, Francisco Igor Macedo MD, Dido Franceschi MD, Alan S. Livingstone MD & Danny Yakoub MD, PhD

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  1. Basem Azab MD
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  2. Julia R. Amundson MD
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Correspondence to Basem Azab MD.

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Azab, B., Amundson, J.R., Picado, O. et al. Impact of Chemoradiation-to-Surgery Interval on Pathological Complete Response and Short- and Long-Term Overall Survival in Esophageal Cancer Patients. Ann Surg Oncol 26, 861–868 (2019). https://doi.org/10.1245/s10434-018-6897-4

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  • DOI: https://doi.org/10.1245/s10434-018-6897-4

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