Pattern of CAIX expression is prognostic for outcome and predicts response to ARCON in patients with laryngeal cancer treated in a phase III randomized trial

Saskia E. Rademakers*, Ilse J. Hoogsteen, Paul F. Rijken, Egbert Oosterwijk, Chris H. Terhaard, Patricia A. Doornaert, Johannes A. Langendijk, Piet van den Ende, Robert Takes, Remco De Bree, Albert J. Van der Kogel, Johan Bussink, Johannes H. Kaanders

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

Abstract

Background and purpose: In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON (accelerated radiotherapy with carbogen breathing and nicotinamide) to accelerated radiotherapy alone (AR) the prognostic and predictive value of CAIX, a hypoxia-associated protein, was investigated.

Material and methods: 261 Paraffin embedded tumor biopsies and 79 fresh frozen biopsies from patients entered in the trial were immunohistochemically stained for CAIX. CAIX-fraction and CAIX expression pattern were related to tumor control and patient survival.

Results: Low CAIX-fraction was prognostic for worse regional control and overall survival in patients treated with AR. Patients with a low CAIX-fraction treated with ARCON had better regional control and metastasis-free survival compared to AR (RC 97% vs 71%, p <0.01 and MFS 92% vs 69%, p = 0.06).

Patients with a perinecrotic CAIX staining pattern had a significantly worse local control, metastasis-free and overall survival compared to patients with a diffuse pattern (65% vs 84%, p = 0.01, 70% vs 96%, p <0.01 and 42% vs 71%, p <0.01 respectively), and this could not be improved with ARCON. After multivariate analysis CAIX pattern and N-stage emerged as significant predictors for metastasis-free survival and overall survival.

Conclusions: ARCON improves regional control and metastasis-free survival only in patients with low CAIX expression. The different patterns of CAIX expression suggest different mechanisms of upregulation and have important prognostic value. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)517-522
Number of pages6
JournalRadiotherapy and Oncology
Volume108
Issue number3
DOIs
Publication statusPublished - Sep-2013

Keywords

  • ARCON
  • CAIX
  • Hypoxia
  • Laryngeal cancer
  • CARBONIC-ANHYDRASE-IX
  • SQUAMOUS-CELL-CARCINOMA
  • INDUCIBLE FACTOR 1-ALPHA
  • HIF-1-ALPHA EXPRESSION
  • HUMAN-PAPILLOMAVIRUS
  • TUMOR ANGIOGENESIS
  • BREAST-CANCER
  • NECK-CANCER
  • HUMAN HEAD
  • HYPOXIA

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