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Definitive radiation therapy for treatment of laryngeal carcinoma

Impact of local relapse on outcome and implications for treatment strategies

Primäre Strahlentherapie zur Behandlung des Larynxkarzinoms

Einfluss des Lokalrezidivs auf den Behandlungserfolg und Implikationen für Behandlungsstrategien

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Abstract

Purpose

The purpose of this work was to evaluate outcome after radiotherapy (RT) for laryngeal carcinoma and investigate effects of local relapse on ultimate disease control, including surgical salvage procedures.

Methods and materials

In all, 435 patients with laryngeal carcinoma (cT1–cT4a) treated with primary RT were retrospectively analyzed. Uni- and multivariate analyses were performed to identify prognostic factors for local relapse-free survival and overall survival.

Results

Median follow-up was 38 months (range 1–144 months). The cumulative frequency of local recurrence was dependent on T stage: cT1 tumors 10 %, cT2 18 %, cT3 23 %, and cT4 36 % (p < 0.001). Salvage surgery for local persistent/recurrent disease was performed in 59 of 78 patients (76 %). The ultimate local control rates at 5 years (including salvage therapy) were 98, 98, 87, and 68 % for cT1, cT2, cT3, and cT4 tumors (p < 0.001), respectively. For the patients who developed local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and 26 % (p < 0.001), respectively. Overall survival at 5 years was 68 % for patients without local relapse and 50 % for patients experiencing local failure (p < 0.001). In univariate analysis, cT stage, cN stage, and tumor volume were statistically significant associated with local relapse-free survival. In multivariate analysis for the cT3–4 tumors, only tumor volume remained statistically significant (HR 1.017, p = 0.001) for local relapse-free survival.

Conclusion

Local control rates for cT1–2 laryngeal carcinomas are favorable and in concordance with previous reports and most recurrences are salvaged. For cT3–4 tumors treated with RT alone, initial local control rates are moderate, and in 60 % of recurring cases salvage surgery is attempted, with ultimate local control being achieved in only a subset. For voluminous, locally advanced laryngeal tumors, more aggressive treatment modalities should be considered, including upfront laryngectomy or radiochemotherapy.

Zusammenfassung

Ziel

Evaluation der Behandlungsergebnisse nach Strahlentherapie (RT) für Larynxkarzinome und Untersuchung des Effekts von Lokalrezidiven auf die Tumorkontrolle, einschließlich chirurgischer Salvage-Prozeduren.

Material und Methoden

Retrospektive Analyse von 435 Patienten mit Larynxkarzinom (cT1–cT4a), die mit primärer RT behandelt wurden. Uni- und multivariate Analysen wurden ausgeführt, um prognostische Faktoren für lokalrezidivfreies Überleben und Gesamtüberleben zu identifizieren.

Ergebnisse

Das mediane Follow-up betrug 38 Monate (Spanne 1–144 Monate). Die kumulative Frequenz von Lokalrezidiven hing vom cT-Stadium ab: cT1-Tumore 10 %, cT2 18 %, cT3 23 % und cT4 36 % (p < 0,001). Eine Salvage-Chirurgie für lokal persistierende oder rezidivierende Malignität wurde in 59 der 78 Patienten durchgeführt (76 %). Die endgültige lokale Kontrolle nach 5 Jahren (einschließlich Salvage-Behandlung) betrug jeweils 98, 98, 87 und 68 % für cT1-, cT2-, cT3- und cT4-Tumoren (p < 0,001). Für Patienten mit einem Lokalrezidiv war die entsprechende lokale Kontrolle jeweils 80, 88, 55 und 26 % (p < 0,001). Das Gesamtüberleben nach 5 Jahren betrug 68 % für Patienten ohne Lokalrezidiv und 50 % für Patienten mit Lokalrezidiv (p < 0,001). Bei univariater Analyse waren cT-Stadium, cN-Stadium und Tumorvolumen statistisch signifikant mit lokalrezidivfreiem Überleben korreliert. Bei multivariater Analyse für Tumoren im Stadium cT3–4 blieb nur das Tumorvolumen statistisch signifikant (HR 1,017; p = 0,001).

Schlussfolgerung

Die lokale Kontrolle für Larynxkarzinome im Stadium cT1–2 ist günstig und in Übereinstimmung mit früheren Publikationen; die meisten Lokalrezidive können behandelt werden. Für Tumore im Stadium cT3–4, die nur bestrahlt werden, ist die lokale Tumorkontrolle nur mäßig. Obwohl in 60 % dieser Fälle eine Salvage-Chirurgie ausgeführt wird, ist die endgültige lokale Tumorkontrolle nur in einem Teil der Fälle erreichbar. Für voluminöse, lokal fortgeschrittene Larynxkarzinome sollten aggressivere Behandlungsmodalitäten in Erwägung gezogen werden, einschließlich primärer Larynxextirpation oder Radiochemotherapie.

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Acknowledgments

We acknowledge financial support from CTMM, the Center for Translational Molecular Medicine (http://www.ctmm.nl), project AIRFORCE number 03O–103. European Union sixth and seventh framework program (ARTFORCE and METOXIA), INTERREG (http://www.eurocat.info), QuIC-ConCePT (funded by the Innovative Medicine Initiative Joint Undertaking) and the Dutch Cancer Society (KWF UM 2011–5020 and KWF UM 2009–4454).

Compliance with ethical guidelines

Conflict of interest. F. Hoebers, E. Rios, E. Troost, P. van den Ende, K. Kross, M. Lacko, R. Lalisang, B. Kremer, and J. de Jong 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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Authors and Affiliations

  1. Department of Radiation Oncology (MAASTRO clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Postbox 1345, 6201 BH, Maastricht, The Netherlands

    F. Hoebers MD PhD, E. Rios, E. Troost MD PhD, P. van den Ende MD & J. de Jong MD PhD

  2. Department of Otorhinolaryngology–Head and Neck Surgery, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre+, Maastricht, The Netherlands

    K. Kross MD PhD, M. Lacko MD PhD & B. Kremer MD PhD

  3. Division of Medical Oncology, Department of Internal Medicine, GROW-School of Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands

    R. Lalisang MD PhD

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  1. F. Hoebers MD PhD
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  2. E. Rios
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  3. E. Troost MD PhD
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  4. P. van den Ende MD
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  6. M. Lacko MD PhD
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  7. R. Lalisang MD PhD
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  8. B. Kremer MD PhD
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  9. J. de Jong MD PhD
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Corresponding author

Correspondence to F. Hoebers MD PhD.

Additional information

F. Hoebers and E. Rios contributed equally to this work.

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Hoebers, F., Rios, E., Troost, E. et al. Definitive radiation therapy for treatment of laryngeal carcinoma. Strahlenther Onkol 189, 834–841 (2013). https://doi.org/10.1007/s00066-013-0414-2

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  • DOI: https://doi.org/10.1007/s00066-013-0414-2

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