Skip to main content

Advertisement

SpringerLink
Log in

Neoadjuvant chemoradiation for esophageal cancer

Surgery improves locoregional control while response based on FDG-PET/CT predicts survival

Neoadjuvante Radiochemotherapie beim Ösophaguskarzinom

Operation verbessert lokale Kontrolle und Ansprechen in der FDG-PET/CT korreliert mit Überleben

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Introduction

To retrospectively analyze the outcome of patients with esophageal cancer treated with neoadjuvant chemoradiation.

Methods

A total of 41 patients received neoadjuvant intent chemoradiation for esophageal cancer. Most patients had a locally advanced disease (T3/4: 82%, N+: 83%, M0: 100%) and squamous cell carcinoma (83%). All patients received concurrent chemotherapy with cisplatin/5-fluorouracil or mitomycin/5-fluorouracil. Median radiation dose was 50.4 Gy in the 25 patients who proceeded to surgery and 57.4 Gy in 16 patients who did not undergo surgery. FDG-PET/CT was used for treatment planning in 24 patients. A second FDG-PET/CT was available for response evaluation in 18 patients.

Results

Median follow-up was 16 months in all patients and 30 months in survivors. Radiotherapy was completed without interruptions >3 days in 90% of patients, and chemotherapy was carried out to >80% in 85% of patients. The 2‑year locoregional control rate was 60%, distant control rate 54% and overall survival rate 50%. Hematological toxicity grade 3/4 was observed in 34%/10% of patients and non-hematological toxicity grade 3/4 in 46%/2% of patients. Perioperative 30-day mortality was 4%. Subgroup analyses revealed that surgery significantly improved locoregional control (74% vs. 39%, p = 0.034), but not the 2‑year survival rate (54% vs. 43%, p = 0.246). In contrast, response based on FDG-PET/CT prior and after chemoradiation significantly predicted improved overall survival (2-year overall survival 61% vs. 40%, p = 0.048).

Conclusion

Outcomes of our cohort were comparable to other series using similar treatments. Surgery significantly improved locoregional control but not survival. Response based on FDG-PET/CT predicted survival and might be used for treatment stratification.

Zusammenfassung

Einleitung

Patienten mit Ösophaguskarzinom wurden nach neoadjuvanter Radiochemotherapie retrospektiv ausgewertet.

Methoden

Insgesamt 41 Patienten mit Ösophaguskarzinom erhielten eine neoadjuvant intendierte Radiochemotherapie. Die meisten Patienten hatten ein lokal fortgeschrittenes Plattenepithelkarzinom des Ösophagus (T3/4: 82 %, N+: 83 %, M0: 100 %). Alle Patienten erhielten eine konkomitante Chemotherapie mit Cisplatin/5-Fluorouracil oder Mitomycin/5-Fluorouracil. Die mediane Gesamtdosis der 25 operierten Patienten betrug 50,4 Gy und die der 16 letztlich definitiv bestrahlten nichtoperierten Patienten 57,4 Gy. Vor Beginn der Radiochemotherapie hatten 24 Patienten eine FDG-PET/CT erhalten und 18 Patienten eine zweite FDG-PET/CT zum Erheben des Ansprechens nach Neoadjuvanz.

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 16 Monate für alle Patienten und 30 Monate für Überlebende. Bei 90 % der Patienten konnte die Strahlentherapie ohne Unterbrechung von >3 Tagen durchgeführt werden und 85 % der Patienten erhielten ≥80 % der vorgesehenen Gesamtdosis an Chemotherapie. Die 2‑Jahres-Lokalkontrollrate lag bei 60 %, die distante Kontrollrate bei 54 % und das Gesamtüberleben bei 50 %. Hämatologische Nebenwirkungen vom Grad 3/4 traten bei 34 %/10 % und nichthämatologische Nebenwirkungen vom Grad 3/4 bei 46 %/2 % auf. Die postoperative 30-Tage-Mortalität betrug 4 %. Subgruppenanalysen ergaben, dass eine Operation signifikant die lokale Kontrolle (74 % vs. 39 %; p = 0,034), nicht aber das 2‑Jahres-Überleben (54 % vs. 43 %; p = 0,246) beeinflusst. Hingegen korreliert ein Ansprechen nach Radiochemotherapie in der FDG-PET/CT positiv mit dem 2‑Jahres-Überleben (61 % vs. 40 %; p = 0,048).

Schlussfolgerung

Die Ergebnisse unserer Kohorte sind vergleichbar mit anderen Studien mit ähnlichen Therapiekonzepten. Die Operation verbesserte signifikant die lokale Kontrolle, nicht aber das Überleben. Ein Ansprechen in der FDG-PET/CT korrelierte positiv mit dem Überleben unserer Patienten und könnte für eine Therapiestratifizierung herangezogen werden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Shapiro J, van Lanschot JJ, Hulshof MC et al (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16:1090–1098

    Article  PubMed  Google Scholar 

  2. Burmeister BH, Smithers BM, Gebski VB et al (2005) Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol 6:659–668

    Article  PubMed  Google Scholar 

  3. Walsh TN, Noonan N, Hollywood D et al (1996) A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335:462–467

    Article  CAS  PubMed  Google Scholar 

  4. Stahl M, Walz MK, Stuschke M et al (2009) Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27:851–856

    Article  CAS  PubMed  Google Scholar 

  5. Davies AR, Gossage JA, Zylstra J et al (2014) Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol 32:2983–2990

    Article  PubMed  Google Scholar 

  6. Zenda S, Kojima T, Kato K (2016) Multicenter phase 2 study of cisplatin and 5‑fluorouracil with concurrent radiation therapy as an organ preservation approach in patients with squamous cell carcinoma of the cervical esophagus. Int J Radiat Oncol Biol Phys 96:976–984

    Article  CAS  PubMed  Google Scholar 

  7. Ilson DH, Minsky BD, Ku GY et al (2012) Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer. Cancer 118:2820–2827

    Article  CAS  PubMed  Google Scholar 

  8. Tepper J, Krasna MJ, Niedzwiecki D et al (2008) Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26:1086–1092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vincent J, Mariette C, Pezet D et al (2015) Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone. Eur J Cancer 51:1683–1693

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Macdonald JS, Smalley SR, Benedetti J et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730

    Article  CAS  PubMed  Google Scholar 

  12. Kelsen DP, Winter KA, Gunderson LL (2007) Long-term results of RTOG trial 8911 (USA intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol 25:3719–3725

    Article  PubMed  Google Scholar 

  13. Allum WH, Stenning SP, Bancewicz J et al (2009) Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol 27:5062–5067

    Article  PubMed  Google Scholar 

  14. Ychou M, Boige V, Pignon JP et al (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29:1715–1721

    Article  CAS  PubMed  Google Scholar 

  15. Nicolay NH, Rademacher J, Oelmann-Avendano J et al (2016) High dose-rate endoluminal brachytherapy for primary and recurrent esophageal cancer. Strahlenther Onkol 192:458–466

    Article  PubMed  Google Scholar 

  16. Yu WW, Zhu ZF, Fu XL et al (2014) Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma. Strahlenther Onkol 190:979–986

    Article  PubMed  Google Scholar 

  17. Ordu AD, Nieder C, Geinitz H et al (2015) Radio(chemo)therapy for locally advanced squamous cell carcinoma of the esophagus. Strahlenther Onkol 191:153–160

    Article  PubMed  Google Scholar 

  18. Fakhrian K, Ordu AD, Lordick F et al (2014) Long-term outcomes of trimodality treatment for squamous cell carcinoma of the esophagus with cisplatin and/or 5‑FU. Strahlenther Onkol 190:1133–1140

    Article  PubMed  Google Scholar 

  19. Fakhrian K, Ordu AD, Haller B et al (2014) Cisplatin- vs. oxaliplatin-based radiosensitizing chemotherapy for squamous cell carcinoma of the esophagus. Strahlenther Onkol 190:987–992

    Article  CAS  PubMed  Google Scholar 

  20. G. A. o. t. W. M. Association (2014) World medical association declaration of helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent 81:14–18

    Google Scholar 

  21. Wahl RL, Jacene H, Kasamon Y et al (2009) From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med 50:122–150

    Article  Google Scholar 

  22. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cooper JS, Guo MD, Herskovic A et al (1999) Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 281:1623–1627

    Article  CAS  PubMed  Google Scholar 

  24. Stahl M, Stuschke M, Lehmann N et al (2005) Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23:2310–2317

    Article  PubMed  Google Scholar 

  25. Bedenne L, Michel P, Bouché O et al (2007) Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25:1160–1168

    Article  CAS  PubMed  Google Scholar 

  26. Brücher BL, Weber W, Bauer M et al (2001) Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography. Ann Surg 233:300–309

    Article  PubMed  PubMed Central  Google Scholar 

  27. Flamen P, Van Cutsem E, Lerut A et al (2002) Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer. Ann Oncol 13:361–368

    Article  CAS  PubMed  Google Scholar 

  28. Downey RJ, Akhurst T, Ilson D et al (2003) Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol 21:428–432

    Article  PubMed  Google Scholar 

  29. Ogino I, Watanabe S, Iwahashi N et al (2016) Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer. Strahlenther Onkol 192:359–367

    Article  PubMed  Google Scholar 

  30. Dhami G, Zeng J, Vesselle HJ et al (2017) Framework for radiation pneumonitis risk stratification based on anatomic and perfused lung dosimetry. Strahlenther Onkol. https://doi.org/10.1007/s00066-017-1114-0

    PubMed  Google Scholar 

  31. Moureau-Zabotto L, Touboul E, Lerouge D et al (2005) Impact of CT and 18F-deoxyglucose positron emission tomography image fusion for conformal radiotherapy in esophageal carcinoma. Int J Radiat Oncol Biol Phys 63:340–345

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Munich (LMU), Marchioninistr. 15, 81377, Munich, Germany

    Nina-Sophie Hegemann, Rebecca Koepple,  Franziska Walter, David Boeckle,  Claus Belka &  Falk Roeder

  2. Department of Nuclear Medicine, University of Munich (LMU), Munich, Germany

    Wolfgang P. Fendler

  3. Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University of Munich (LMU), Munich, Germany

    Martin Kurt Angele

  4. Department of Internal Medicine III—Medical Oncology, University of Munich (LMU), Munich, Germany

    Stefan Boeck

  5. CCU Molecular Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Falk Roeder

Authors
  1. Nina-Sophie Hegemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca Koepple
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Franziska Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Boeckle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wolfgang P. Fendler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martin Kurt Angele
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stefan Boeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Claus Belka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Falk Roeder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nina-Sophie Hegemann.

Ethics declarations

Conflict of interest

N.-S. Hegemann, R. Koepple, F. Walter, D. Boeckle, W.P. Fendler, M.K. Angele, S. Boeck, C. Belka and F. Roeder declare that they have no competing interests.

Ethical standards

This retrospective analysis was performed according to the principles of the Declaration of Helsinki and its subsequent amendments [20]. This retrospective analysis was approved by the local ethics committee. All patients gave written informed consent prior to treatment start.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hegemann, NS., Koepple, R., Walter, F. et al. Neoadjuvant chemoradiation for esophageal cancer. Strahlenther Onkol 194, 435–443 (2018). https://doi.org/10.1007/s00066-018-1261-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-018-1261-y

Keywords

Schlüsselwörter

Search

Navigation