Strahlentherapie und Onkologie

, Volume 189, Issue 10, pp 834–841 | Cite as

Definitive radiation therapy for treatment of laryngeal carcinoma

Impact of local relapse on outcome and implications for treatment strategies
  • F. Hoebers
  • E. Rios
  • E. Troost
  • P. van den Ende
  • K. Kross
  • M. Lacko
  • R. Lalisang
  • B. Kremer
  • J. de Jong
Original article



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.


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.


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.


Laryngeal carcinoma Radiotherapy Chemoradiation Surgery Laryngectomy 

Primäre Strahlentherapie zur Behandlung des Larynxkarzinoms

Einfluss des Lokalrezidivs auf den Behandlungserfolg und Implikationen für Behandlungsstrategien



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.


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).


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.


Larynxkarzinom Strahlentherapie Radiochemotherapie Chirurgie Laryngektomie 


  1. 1.
    Hartl DM, Ferlito A, Brasnu DF et al (2011) Evidence-based review of treatment options for patients with glottic cancer. Head Neck 33:1638–1648PubMedCrossRefGoogle Scholar
  2. 2.
    Remmelts AJ, Hoebers FJ, Klop WM et al (2013) Evaluation of laser surgery and radiotherapy as treatment modalities in early stage laryngeal carcinoma: tumour outcome and quality of voice. Eur Arch Otorhinolaryngol 270:2079–2087PubMedCrossRefGoogle Scholar
  3. 3.
    Wolf GT, Fisher SG, Hong WK et al (1991) Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs laryngeal cancer study group. N Engl J Med 324:1685–1690CrossRefGoogle Scholar
  4. 4.
    Forastiere AA, Goepfert H, Maor M et al (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349:2091–2098PubMedCrossRefGoogle Scholar
  5. 5.
    Forastiere AA, Zhang Q, Weber RS et al (2013) Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31:845–852PubMedCrossRefGoogle Scholar
  6. 6.
    Bourhis J, Overgaard J, Audry H et al (2006) Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 368:843–854PubMedCrossRefGoogle Scholar
  7. 7.
    Johansen LV, Overgaard J, Elbrond O (1988) Pharyngo-cutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole. Cancer 61:673–678PubMedCrossRefGoogle Scholar
  8. 8.
    Janssens GO, Rademakers SE, Terhaard CH et al (2012) Accelerated radiotherapy with carbogen and nicotinamide for laryngeal cancer: results of a phase III randomized trial. J Clin Oncol 30:1777–1783PubMedCrossRefGoogle Scholar
  9. 9.
    Voet JC van der, Keus RB, Hart AA et al (1998) The impact of treatment time and smoking on local control and complications in T1 glottic cancer. Int J Radiat Oncol Biol Phys 42:247–255PubMedCrossRefGoogle Scholar
  10. 10.
    Mendenhall WM, Werning JW, Hinerman RW et al (2004) Management of T1-T2 glottic carcinomas. Cancer 100:1786–1792PubMedCrossRefGoogle Scholar
  11. 11.
    Pfister DG, Laurie SA, Weinstein GS et al (2006) American society of clinical oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer. J Clin Oncol 24:3693–3704PubMedCrossRefGoogle Scholar
  12. 12.
    Hoffman HT, Porter K, Karnell LH et al (2006) Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival. Laryngoscope 116:1–13PubMedCrossRefGoogle Scholar
  13. 13.
    Chen AY, Halpern M (2007) Factors predictive of survival in advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg 133:1270–1276PubMedCrossRefGoogle Scholar
  14. 14.
    Gourin CG, Conger BT, Sheils WC et al (2009) The effect of treatment on survival in patients with advanced laryngeal carcinoma. Laryngoscope 119:1312–1317PubMedCrossRefGoogle Scholar
  15. 15.
    Nguyen NP, Moltz CC, Frank C et al (2004) Dysphagia following chemoradiation for locally advanced head and neck cancer. Ann Oncol 15:383–388PubMedCrossRefGoogle Scholar
  16. 16.
    Eisbruch A, Lyden T, Bradford CR et al (2002) Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 53:23–28PubMedCrossRefGoogle Scholar
  17. 17.
    Pameijer FA, Mancuso AA, Mendenhall WM et al (1997) Can pretreatment computed tomography predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy? Int J Radiat Oncol Biol Phys 37:1011–1021PubMedCrossRefGoogle Scholar
  18. 18.
    Knegjens JL, Hauptmann M, Pameijer FA et al (2011) Tumor volume as prognostic factor in chemoradiation for advanced head and neck cancer. Head Neck 33:375–382PubMedGoogle Scholar
  19. 19.
    Al-Mamgani A, Tans L, Rooij P van, Levendag PC (2012) A single-institutional experience of 15 years of treating T3 laryngeal cancer with primary radiotherapy, with or without chemotherapy. Int J Radiat Oncol Biol Phys 83:1000–1006PubMedCrossRefGoogle Scholar
  20. 20.
    Vokes EE (2013) Competing roads to larynx preservation. J Clin Oncol 31:833–835PubMedCrossRefGoogle Scholar
  21. 21.
    Bourhis J, Sire C, Graff P et al (2012) Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99–02): an open-label phase 3 randomised trial. Lancet Oncol 13:145–153PubMedCrossRefGoogle Scholar
  22. 22.
    Lambin P, van Stiphout RG, Starmans MH et al (2013) Predicting outcomes in radiation oncology—multifactorial decision support systems. Nat Rev Clin Oncol 10:27–40PubMedCrossRefGoogle Scholar
  23. 23.
    Dionysopoulos D, Pavlakis K, Kotoula V et al (2013) Cyclin D1, EGFR, and Akt/mTOR pathway. Potential prognostic markers in localized laryngeal squamous cell carcinoma. Strahlenther Onkol 189:202–214PubMedCrossRefGoogle Scholar
  24. 24.
    Egelmeer AG, Velazquez ER, de Jong JM et al (2010) Development and validation of a nomogram for prediction of survival and local control in laryngeal carcinoma patients treated with radiotherapy alone: a cohort study based on 994 patients. Radiother Oncol 100:108–115CrossRefGoogle Scholar
  25. 25.
    Lambin P, Rios-Velazquez E, Leijenaar R et al (2012) Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer 48:441–446PubMedCrossRefGoogle Scholar

Copyright information

© Springer Heidelberg Berlin 2013

Authors and Affiliations

  • F. Hoebers
    • 1
  • E. Rios
    • 1
  • E. Troost
    • 1
  • P. van den Ende
    • 1
  • K. Kross
    • 2
  • M. Lacko
    • 2
  • R. Lalisang
    • 3
  • B. Kremer
    • 2
  • J. de Jong
    • 1
  1. 1.Department of Radiation Oncology (MAASTRO clinic), GROW School for Oncology and Developmental BiologyMaastricht University Medical Centre+MaastrichtThe Netherlands
  2. 2.Department of Otorhinolaryngology–Head and Neck Surgery, School for Oncology and Developmental Biology (GROW)Maastricht University Medical Centre+MaastrichtThe Netherlands
  3. 3.Division of Medical Oncology, Department of Internal Medicine, GROW-School of Oncology and Developmental BiologyMaastricht University Medical Centre+MaastrichtThe Netherlands

Personalised recommendations