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Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

Die prognostische Bedeutung einer veränderten epidermalen Wachtumsfaktor-Rezeptor-Expression nach neoadjuvanter Chemoradiotherapie bei Patienten mit Rektumkarzinom

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Abstract

Purpose

The aim of the present study was to examine the effect of neoadjuvant chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in patients with locally advanced rectal adenocarcinoma.

Patients and methods

A total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4–6 weeks after the chemoradiation. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry.

Results

Patients with an increase of EGFR expression during chemoradiation had significantly shorter disease-free survival (DFS; p = 0.003) and overall survival (OS; p = 0.005) compared to patients with either no change or decrease in EGFR expression. The 5-year DFS in patients with increased EGFR expression was only 29% compared to 61% in patients without an increase of EGFR expression. Similarly, the 5-year OS of the patients with increased EGFR expression was 29% compared to 66% in patients without an increase of EGFR expression. All recurrences in patients who had an increase of EGFR expression occurred within the first 2 years after the treatment. The increase in EGFR expression was the only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using multivariate Cox regression analysis.

Conclusion

An increase of EGFR expression during chemoradiation may be associated with significantly shorter DFS and OS. The increase of EGFR could identify a population of patients in whom the effect of the treatment with anti-EGFR therapy should be studied.

Zusammenfassung

Ziel

Das Ziel der Studie war die Untersuchung der Wirkung der neoadjuvanten Chemoradiotherapie auf die Expression des epidermalen Wachtumsfaktor-Rezeptors (EGFR) beim Patienten mit lokal fortgeschrittenem Rektumkarzinom.

Patienten und Methodik

Es wurden 53 Patienten mit Rektumkarzinom (klinische Stadien II und III) untersucht. Die neoadjuvante Therapie bestand aus Bestrahlung (50,4 Gy/28 Fraktionen) und konkomitanter kontinuierlicher Infusion von 5-Fluorouracil. Die chirurgische Operation wurde 4–6 Wochen nach dem Ende der Chemoradiotherapie durchgeführt. Die EGFR-Expression wurde immunohistochemisch untersucht. Die Signifikanz der Unterschiede wurde mit dem Log-Rank-Test und der Cox-Regression getestet.

Ergebnisse

Patienten mit einer erhöhten EGFR-Expression während der Chemoradiotherapie hatten signifikant kürzere DFS- (DFS, krankheitsfreies Überleben; p = 0,003) und OS-Zeiten (OS, Gesamtüberleben; p = 0,005). Nach 5 Jahren lag das DFS bei Patienten mit erhöhter EGFR-Expression bei nur 29% im Vergleich zu 61% bei Patienten, bei denen keine Erhöhung der EGFR-Expression beobachtet wurde. Auch die 5-Jahres-Überlebenszeit bei Patienten mit erhöhter EGFR-Expression betrug 29% im Vergleich zu 66% bei Patienten ohne Erhöhung. Alle Rezidive bei Patienten mit gesteigerter EGFR-Expression wurden innerhalb von 2 Jahren nach Therapie beobachtet. Die Erhöhung der EGFR-Expression war in der multivarianten Cox-Regression der einzige signifikante Vorhersagefaktor von DFS (p = 0,007) und OS (p = 0,04).

Schlussfolgerung

Eine Erhöhung der EGFR-Expression während der Chemoradiotherapie kann in signifikant kürzeren DFS- und OS-Zeiten resultieren. Anhand dieser Erhöhung lässt sich eine Patientenpopulation identifizieren, bei der man eine anti-EGFR-Therapie prüfen sollte.

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Acknowledgments

This work was supported by the Research Project MZO 00179906 and the Internal Grant Agency of the Ministry of Health of the Czech Republic NS9690-4.

Conflict of interest

On behalf of all authors, the corresponding author states that.

Author information

Authors and Affiliations

  1. Department of Oncology and Radiotherapy, Charles University Medical School and Teaching Hospital, Sokolska 581, 50005, Hradec Kralove, Czech Republic

    J. Dvorak M.D., Ph.D., I. Sirak M.D., Ph.D. & J. Petera M.D., Ph.D.

  2. Department of Pathology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic

    V. Sitorova M.D., Ph.D., A. Ryska M.D., Ph.D. & J. Hatlova M.D., Ph.D.

  3. Department of Oncology, Regional Hospital Liberec, Liberec, Czech Republic

    I. Richter M.D., Ph.D.

  4. Charles University Medical School, Hradec Kralove, Czech Republic

    I. Richter M.D., Ph.D.

  5. Department of Surgery, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic

    A. Ferko M.D., Ph.D.

  6. Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic

    B. Melichar M.D., Ph.D.

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  1. J. Dvorak M.D., Ph.D.
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Correspondence to J. Dvorak M.D., Ph.D..

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Dvorak, J., Sitorova, V., Ryska, A. et al. Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma. Strahlenther Onkol 188, 833–838 (2012). https://doi.org/10.1007/s00066-012-0160-x

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