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Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck

Der Fibroblastenwachstumsfaktor 2 ist von prognostischer Bedeutung bei Patienten mit lokal fortgeschrittenem Plattenepithelkarzinom der Kopf-Hals-Region

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An Erratum to this article was published on 19 February 2014

Abstract

Background and purpose

Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy.

Patients and methods

The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model.

Results

On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88–19.05; p < 0.001], lower T-category (RR: 2.42; 95 %-CI: 1.47–4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48–78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 4.18; 95 %-CI: 1.73–10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97–2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22–11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38–3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60–10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 3.20; 95 %-CI: 1.46–7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054).

Conclusions

Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials.

Zusammenfassung

Hintergrund und Ziel

Viele Patienten mit lokal fortgeschrittenem Plattenepithelkarzinom der Kopf-Hals-Region (SCCHN) haben eine schlechte Prognose. In dieser Studie wurde die prognostische Bedeutung der Tumorzellexpression des Fibroblastenwachstumsfaktors 2 (FGF-2) bei Patienten untersucht, bei denen aufgrund eines lokal fortgeschrittenen SCCHN eine Operation mit nachfolgender Strahlentherapie durchgeführt worden war.

Patienten und Methoden

Der Einfluss von FGF-2 und 11 weiteren Faktoren auf die lokoregionäre Kontrolle (LRC), das metastasenfreie Überleben (MFS) und das Gesamtüberleben (OS) wurde retrospektiv bei 146 Patienten untersucht. Weitere Faktoren waren Alter, Geschlecht, Allgemeinzustand, Hämoglobinwert vor Bestrahlung, Tumorlokalisation, Grading, T-Kategorie, N-Kategorie, Humanes-Papillomavirus(HPV)-Status, Resektionsausmaß und Chemotherapie. Die univariaten Analysen erfolgten mit der Kaplan-Meier-Methode und dem Log-rank-Test, die Multivarianzanalysen mit dem Proportional-Hazards-Modell nach Cox.

Ergebnisse

In der Multivarianzanalyse war eine verbesserte LRC signifikant mit FGF-2-Negativität (Risk Ratio, RR: 7,33; 95%-Konfidenzintervall, 95%-KI: 2,88–19,05; p < 0,001), niedrigerer T-Kategorie (RR: 2,42; 95%-KI: 1,47–4,33; p < 0,001), niedrigerer N-Kategorie (RR: 12,36; 95%-KI: 3,48–78,91; p < 0,001) und Hämoglobinwerten vor Bestrahlung ≥ 12 g/dl (RR: 4,18; 95%-KI: 1,73–10,53; p = 0,002) assoziiert. Kein Faktor war signifikant mit dem MFS assoziiert. Eine niedrigere T-Kategorie zeigte einen Trend (RR: 1,59; 95%-KI: 0,97–2,82; p = 0,069). Ein besseres OS war signifikant mit FGF-2-Negativität (RR: 5,10; 2,22–11,80; p < 0,001), niedrigerer T-Kategorie (RR: 2,17; 95%-KI: 1,38–3,68; p < 0,001), niedrigerer N-Kategorie (RR: 3,86; 95%-KI: 1,60–10,85; p = 0,002) und Hämoglobinwerten ≥ 12 g/dl (RR: 3,20; 95%-KI: 1,46–7,30; p = 0,004) assoziiert. HPV-Positivität zeigte einen Trend (RR: 2,36; 95%-KI: n.a.; p = 0,054).

Schlussfolgerung

Die Tumorexpression von FGF-2 erwies sich als unabhängiger Prognosefaktor für LRC und OS. Dieser Faktor kann bei der Personalisierung der Therapie und der Stratifikation in zukünftigen Studien helfen.

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Conflict of interest

The corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    D. Rades M.D. & N.D. Seibold

  2. Institute of Pathology, University of Lübeck, Lübeck, Germany

    M.P. Gebhard & F. Noack

  3. Department of Radiation Oncology, Mayo Clinic Scottsdale, Scottsdale, USA

    S.E. Schild

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  1. D. Rades M.D.
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  2. N.D. Seibold
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  3. M.P. Gebhard
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  4. F. Noack
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Correspondence to D. Rades M.D..

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An erratum to this article is available at http://dx.doi.org/10.1007/s00066-013-0546-4.

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Rades, D., Seibold, N., Gebhard, M. et al. Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck. Strahlenther Onkol 190, 68–74 (2014). https://doi.org/10.1007/s00066-013-0368-4

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