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Re-irradiation with cetuximab or cisplatin-based chemotherapy for recurrent squamous cell carcinoma of the head and neck

Rebestrahlung mit Cetuximab oder cisplatinbasierter Chemotherapie bei rezidivierten Plattenepithelkarzinomen der Kopf-Hals-Region

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An Erratum to this article was published on 04 August 2015

Abstract

Purpose

Locoregional recurrence remains the main pattern of failure after primary combined modality treatment of squamous cell carcinoma of the head and neck (SCCHN). We compared the efficacy and toxicity of either cisplatin or cetuximab in combination with re-irradiation (ReRT) for recurrent unresectable SCCHN. Various clinicopathological factors were investigated to establish a prognostic score.

Patients and methods

Between 2007 and 2014, 66 patients with recurrent SCCHN originating in a previously irradiated area received cetuximab (n = 33) or cisplatin-based chemotherapy (n = 33) concomitant with ReRT. Toxicity was evaluated weekly and at every follow-up visit. Physical examination, endoscopy, CT or MRI scans were used to evaluate response and disease control.

Results

With a mean follow-up of 18.3 months, the 1-year overall survival (OS) rates for Re-RT with cetuximab and cisplatin-based chemotherapy were 44.4 and 45.5 % (p = 0.352), respectively. At 1 year, local control rates (LCR) were 46.4 and 54.2 % (p = 0.625), freedom from metastases (FFM) rates 73.6 and 81 % (p = 0.842), respectively. Haematological toxicity ≥ grade 3 occurred more often in the cisplatin group (p < 0.001), pain ≥ grade 3 was increased in the cetuximab group (p = 0.034). A physiological haemoglobin level and a longer interval between primary RT and ReRT, proved to be significant prognostic factors for OS (multivariate: p = 0.003, p = 0.002, respectively). Site of the recurrence and gross target volume (GTV) did not show a significant impact on OS in multivariate analysis (p = 0.160, p = 0.167, respectively). A prognostic-score (1–4 points) based on these four variables identified significantly different subgroups: 1-year OS for 0/1/2/3/4 prognostic points: 10, 38, 76, 80 and 100 %, respectively (p < 0.001).

Conclusion

Both cetuximab- and cisplatin-based ReRT of SCCHN recurrences are feasible and effective treatment options with comparable results in terms of tumour control and survival. Acute adverse events may differ slightly. Our prognostic score could help to identify appropriate patients for ReRT and stratify patients within future clinical trials.

Zusammenfassung

Ziel

Lokoregionäre Rezidive sind der Hauptgrund für ein Therapieversagen nach primärer multimodaler Behandlung von Plattenepithelkarzinomen der Kopf-Hals-Region (SCCHN). Verglichen wurde die Effektivität und Toxizität von Cisplatin oder Cetuximab simultan zur Rebestrahlung (ReRT) bei inoperablen SCCHN-Rezidiven. Ein prognostischer Score sollte auf Grundlage verschiedener klinischer und pathologischer Faktoren etabliert werden.

Patienten und Methoden

Von 2007 bis 2014 wurden 66 Patienten mit in vorbestrahlten Regionen rezidivierten SCCHN simultan mit Cetuximab (n = 33) oder cisplatinbasierter Chemotherapie (n = 33) rebestrahlt. Die Toxizität wurde wöchentlich sowie bei jedem Nachsorgetermin erfasst. Klinische Untersuchung, Endoskopie, CT- oder MRT-Untersuchungen wurden zur Beurteilung des Therapieansprechens und der Krankheitskontrolle eingesetzt.

Ergebnisse

Nach einer mittleren Nachbeobachtungszeit von 18,3 Monaten betrug das 1-Jahres-Überleben (OS) für ReRT mit Cetuximab 44,4 % und mit cisplatinbasierter Chemotherapie 45,5 % (p = 0,352). Die lokalen Kontollraten nach einem Jahr waren jeweils 46,4 und 54,2 % (p = 0,625); die Raten an Metastasenfreiheit 73,6 und 81 % (p = 0,842). Hämatologische Toxizität ≥ Grad 3 kam in der Cisplatin-Gruppe häufiger vor (p < 0,001), dagegen trat Schmerz ≥ Grad 3 in der Cetuximab-Gruppe häufiger auf (p = 0,034). Ein physiologischer Hb-Wert und ein längeres Intervall zwischen primärer RT und ReRT erwiesen sich als signifikante prognostische Faktoren für das OS (multivariat jeweils p = 0,003 und p = 0,002). Die Rezidivlokalisation sowie das Gesamtzielvolumen (GTV) zeigten keinen signifikanten Einfluss auf das OS in der multivariaten Analyse (jeweils p = 0,160 und p = 0,167). Ein auf Grundlage dieser Variablen konstruierter Prognose-Score (0–4 Punkte) zeigte signifikante Überlebensunterschiede: 1-Jahres-OS für 0–4 Prognosepunkte: jeweils 10, 38, 76, 80 und 100 % (p < 0,001).

Schlussfolgerung

Sowohl Cetuximab- als auch cisplatinbasierte ReRT für SCCHN-Rezidive sind gut durchführbare und effektive Behandlungsoptionen mit vergleichbaren Ergebnissen bezüglich Tumorkontrolle und Überleben. Die akuten Nebenwirkungen könnten gering variieren. Unser Prognose-Score könnte zur Identifizierung der für ReRT geeigneten Patienten sowie zur Stratifizierung in künftigen klinischen Studien dienen.

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Authors and Affiliations

  1. Department of Radiotherapy and Oncology, J. W. Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt a. M., Germany

    Nicolas Dornoff, Christian Weiß M.D., Franz Rödel Ph.D., Nateghian Atefeh, Claus Rödel M.D. & Panagiotis Balermpas M.D.

  2. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Nateghian Atefeh, Claus Rödel M.D. & Panagiotis Balermpas M.D.

  3. German Cancer Consortium (DKTK) partner site: Frankfurt, Frankfurt a. M., Germany

    Nateghian Atefeh, Claus Rödel M.D. & Panagiotis Balermpas M.D.

  4. Department of Otorhinolaryngology, J. W. Goethe University, Frankfurt a. M., Germany

    Jens Wagenblast M.D.

  5. Department of Maxillofacial Surgery, J. W. Goethe University, Frankfurt a. M., Germany

    Shahram Ghanaati M.D.

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  1. Nicolas Dornoff
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Correspondence to Panagiotis Balermpas M.D..

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Conflict of interest:

Drs. Weiss and C. Rödel received payments for lectures and Dr. C. Rödel grants from Merck Serono Darmstadt for past investigations.

N. Dornoff, F. Rödel, J. Wagenblast, S. Ghanaati, N. Atefeh and P. Balermpas state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Dornoff, N., Weiß, C., Rödel, F. et al. Re-irradiation with cetuximab or cisplatin-based chemotherapy for recurrent squamous cell carcinoma of the head and neck. Strahlenther Onkol 191, 656–664 (2015). https://doi.org/10.1007/s00066-015-0854-y

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  • DOI: https://doi.org/10.1007/s00066-015-0854-y

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