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Long-term outcomes of trimodality treatment for squamous cell carcinoma of the esophagus with cisplatin and/or 5-FU

More than 20 years’ experience at a single institution

Langzeitergebnisse der trimodalen Therapie des Ösophagusplattenepithelkarzinoms mit Cisplatin und/oder 5-FU

Mehr als 20 Jahre Erfahrung an einem einzigen Institut

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Abstract

Purpose

The purpose of this article is to report the outcome of neoadjuvant radiochemotherapy (N-RCT) + surgery in patients with squamous cell carcinoma of the esophagus at a single institution.

Methods

We retrospectively reviewed data from patients who were referred to our department for N-RCT. From 1988–2011, 103 patients were treated with N-RCT with cisplatin and/or 5-fluorouracil (5-FU). Group 1: (n = 55) from 1988–2006 with 39.6–40 Gy and 5-FU with (n = 17) or without cisplatin (n = 38). Group 2: from 2003–2010 with 44–45 Gy and 5-FU with (n = 40) or without cisplatin (n = 8). All patients underwent radical resection with reconstruction according to tumor location and 2-field lymph node dissection. The degree of histomorphologic regression was defined as grade 1a (pCR, 0 % residual tumor), grade 1b (pSTR, < 10 % residual tumor), grade 2 (10–50 % residual tumor), and grade 3 (> 50 % residual tumor).

Results

Median follow-up time from the start of N-RCT was 100 months (range 2–213 months). The median overall survival (OS) for the whole cohort was 42 months and the 5-year OS was 45 ± 5 %. In the multivariate analysis, worse ECOG performance status (p < 0.001), weight loss > 10 % before the start of the N-RCT (p = 0.025), higher pT category (p = 0.001), and grade 2/3 pathologic remission (p < 0.001) were significantly associated with a poor OS. PCR and pSTR rates for group 1 were 36 % and 18 % compared to 53 % and 22 % for group 2 (p = 0.011). There was a tendency for a better outcome in group 2 patients without statistical significance. The 5-year OS, disease-free survival and recurrent-free survival were 36 ± 7 %, 35 ± 6, and 36 ± 7 % for group 1 and 55 ± 7, 49 ± 7, and 53 ± 7 in group 2 (p = 0.117, p = 0.124, and p = 0.087). There was no significant difference between the two groups considering the postoperative morbidity and mortality.

Conclusion

Higher radiation doses and more use of simultaneous cisplatin lead to higher pathologic response rates to N-RCT and may be associated with better survival outcomes. Prospective controlled trials are needed to assess the true value of intensified N-RCT regimens.

Zusammenfassung

Hintergrund

Wir stellen die Ergebnisse von Patienten mit Plattenepithelzellkarzinomen des Ösophagus (ESCC) vor, welche an unserem Institut mit neoadjuvanter Radiochemotherapie (N-RCT) mit Cisplatin und/oder 5-Fluorouracil (5-FU)  plusanschließender Operation behandelt worden sind.

Patienten und Methodik

Wir haben retrospektiv die Daten jener Patienten analysiert, welche sich in unserer Abteilung zur N-RCT vorstellten. Von 1988 bis 2011 wurden 103 Patienten mit N-RCT behandelt. Gruppe 1: Von 1988 bis 2006 mit 39,6–40 Gy und 5-FU (n = 55), mit (n = 17) oder ohne Cisplatin (n = 38). Gruppe 2: Von 2003 bis 2010 mit 44–45 Gy und 5-FU mit (n = 40) oder ohne Cisplatin (n = 8). An allen Patienten wurden anschließend eine radikale Resektion des Ösophagus mit einer der Lokalisation entsprechenden Rekonstruktion und eine 2-Felder-Lymphdissektion vollzogen. Die histomorphologische Remission wurde wie folgt klassifiziert: Grad 1a (komplette Remission, 0 % Resttumor), Grad 1b (partielle/subtotale Remission, < 10 % Resttumor), Grad 2 (10–50 % Resttumor) und Grad 3 (> 50 % Resttumor).

Ergebnisse

Die mediane Nachbeobachtungszeit seit Beginn der N-RCT lag bei 100 Monaten (Intervall 2–213 Monate). Die mediane Gesamtüberlebenszeit (OS) für das gesamte Kollektiv betrug 42 Monate bei einer 5-Jahres-überlebensrate von 45 ± 5 %. In der multivarianten Analyse waren ein schlechterer ECOG-Performance-Status (p < 0,001), ein Gewichtsverlust über 10 % vor Beginn der N-RCT (p = 0,025), ein höherer pT-Status (p = 0,001) und eine pathologische Remission 2./3. Grades (p < 0,015) signifikant mit einem schlechteren OS assoziiert. Eine pathologisch komplette Remission (0 % Resttumor) bzw. subtotale Tumorregression (< 10 % Resttumor) konnten bei 36 % bzw. 18 % der Patienten in Gruppe 1 und bei 55 % bzw. 22 % der Patienten in Gruppe 2 erreicht werden (p = 0,011). Insgesamt gab es die Tendenz für ein besseres Ergebnis für Patienten der Gruppe 2, welche jedoch statistisch nicht signifikant war. Die 5-Jahres-Gesamtüberlebensraten, krankheitsfreies überleben und rezidivfreies überleben in Gruppe 1 waren 36 ± 7 %, 35 ± 6 und 36 ± 7 % bzw. 55 ± 7, 49 ± 7 und 53 ± 7 in Gruppe 2 (p = 0,117, p = 0,124 und p = 0,087). Bezüglich der postoperativen Morbidität und Mortalität gab es keinen signifikanten Unterschied zwischen den beiden Gruppen.

Schlussfolgerung

Eine intensivere N-RCT führte zu einer höheren kompletten Remissionsrate. Kontrollierte randomisierte Studien sind nötig, um zu beurteilen, ob intensivierte N-RCT-Konzepte die Ergebnisse von Patienten mit ESCC verbessern können.

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Conflict of interest

K. Fakhrian, A.D. Ordu, F. Lordick, J. Theisen, B. Haller, T. Omrčen, M. Molls, C. Nieder, and H. Geinitz have made no statement. The accompanying manuscript does not include studies on humans or animals.

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Authors and Affiliations

  1. Department of Radiation Oncology, Marien Hospital Herne and Sankt Josef Hospital Bochum, Ruhr-Universität Bochum, Bochum, Germany

    Khashayar Fakhrian M.D.

  2. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Khashayar Fakhrian M.D., Arif Deniz Ordu M.D., Tomislav Omrčen M.D., Michael Molls M.D. & Hans Geinitz M.D.

  3. University Cancer Center Leipzig (UCCL), University Clinic Leipzig, Leipzig, Germany

    Florian Lordick M.D.

  4. Department of Internal Medicine III (Hematology/Oncology), Technische Universität München, Munich, Germany

    Florian Lordick M.D.

  5. Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Jörg Theisen M.D.

  6. Institute for Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Bernhard Haller

  7. Center of Oncology and Radiotherapy, University Hospital Split, Split, Croatia

    Tomislav Omrčen M.D.

  8. Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodø, and Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

    Carsten Nieder M.D.

  9. Department of Radiation Oncology, Krankenhaus der Barmherzigen Schwestern Linz, Linz, Austria

    Hans Geinitz M.D.

  10. Klinik für Strahlentherapie und Radio-Onkologie, Marienhospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Hölkeskampring 40, 44625, Herne, Germany

    Khashayar Fakhrian M.D.

  11. Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

    Carsten Nieder M.D.

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  1. Khashayar Fakhrian M.D.
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  2. Arif Deniz Ordu M.D.
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  3. Florian Lordick M.D.
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  4. Jörg Theisen M.D.
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  5. Bernhard Haller
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  6. Tomislav Omrčen M.D.
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  7. Michael Molls M.D.
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Correspondence to Khashayar Fakhrian M.D..

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Fakhrian, K., Ordu, A., Lordick, F. et al. Long-term outcomes of trimodality treatment for squamous cell carcinoma of the esophagus with cisplatin and/or 5-FU. Strahlenther Onkol 190, 1133–1140 (2014). https://doi.org/10.1007/s00066-014-0711-4

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  • DOI: https://doi.org/10.1007/s00066-014-0711-4

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