PMID- 37029804 OWN - NLM STAT- MEDLINE DCOM- 20230703 LR - 20230814 IS - 1434-4726 (Electronic) IS - 0937-4477 (Print) IS - 0937-4477 (Linking) VI - 280 IP - 8 DP - 2023 Aug TI - The relation between hypoxia and proliferation biomarkers with radiosensitivity in locally advanced laryngeal cancer. PG - 3801-3809 LID - 10.1007/s00405-023-07951-9 [doi] AB - PURPOSE: Treatment decision-making in advanced-stage laryngeal squamous cell carcinoma (LSCC) is difficult due to the high recurrence rates and the desire to preserve laryngeal functions. New predictive markers for radiosensitivity are needed to facilitate treatment choices. In early stage glottic LSCC treated with primary radiotherapy, expression of hypoxia (HIF-1alpha and CA-IX) and proliferation (Ki-67) tumour markers showed prognostic value for local control. The objective of this study is to examine the prognostic value of tumour markers for hypoxia and proliferation on locoregional recurrent disease and disease-specific mortality in a well-defined cohort of patients with locally advanced LSCC treated with primary, curatively intended radiotherapy. METHODS: In pre-treatment biopsy tissues from a homogeneous cohort of 61 patients with advanced stage (T3-T4, M0) LSCC primarily treated with radiotherapy, expression of HIF-1alpha, CA-IX and Ki-67 was evaluated with immunohistochemistry. Demographic data (age and sex) and clinical data (T- and N-status) were retrospectively collected from the medical records. Cox regression analysis was performed to assess the relation between marker expression, demographic and clinical data, and locoregional recurrence and disease-specific mortality. RESULTS: Patients with high expression of HIF-1alpha developed significantly more often a locoregional recurrence (39%) compared to patients with a low expression (21%) (p = 0.002). The expression of CA-IX and Ki-67 showed no association with locoregional recurrent disease. HIF-1alpha, CA-IX and Ki-67 were not significantly related to disease-specific mortality. Clinical N-status was an independent predictor of recurrent disease (p < 0.001) and disease-specific mortality (p = 0.003). Age, sex and T-status were not related to locoregional recurrent disease or disease-specific mortality. CONCLUSION: HIF-1alpha overexpression and the presence of regional lymph node metastases at diagnosis were independent predictors of locoregional recurrent disease after primary treatment with curatively intended radiotherapy in patients with locally advanced LSCC. CI - (c) 2023. The Author(s). FAU - van den Bovenkamp, Karlijn AU - van den Bovenkamp K AD - Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - van der Vegt, Bert AU - van der Vegt B AD - Department of Pathology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ, Groningen, The Netherlands. FAU - Halmos, Gyorgy B AU - Halmos GB AD - Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Slagter-Menkema, Lorian AU - Slagter-Menkema L AD - Department of Pathology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ, Groningen, The Netherlands. FAU - Langendijk, Johannes A AU - Langendijk JA AD - Department of Radiotherapy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - van Dijk, Boukje A C AU - van Dijk BAC AD - Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. AD - Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands. FAU - Schuuring, Ed AU - Schuuring E AUID- ORCID: 0000-0003-3655-143X AD - Department of Pathology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ, Groningen, The Netherlands. e.schuuring@umcg.nl. FAU - van der Laan, Bernard F A M AU - van der Laan BFAM AD - Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. AD - Department of Otorhinolaryngology/Head and Neck Surgery, Haaglanden Medical Center, The Hague, The Netherlands. LA - eng PT - Journal Article DEP - 20230408 PL - Germany TA - Eur Arch Otorhinolaryngol JT - European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery JID - 9002937 RN - 0 (Ki-67 Antigen) RN - EC 4.2.1.1 (Carbonic Anhydrases) RN - 0 (Biomarkers, Tumor) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) SB - IM MH - Humans MH - *Laryngeal Neoplasms/pathology MH - Retrospective Studies MH - Ki-67 Antigen MH - *Carbonic Anhydrases/metabolism MH - *Carcinoma, Squamous Cell MH - Neoplasm Recurrence, Local/pathology MH - Prognosis MH - Squamous Cell Carcinoma of Head and Neck MH - Hypoxia MH - Biomarkers, Tumor/metabolism MH - Radiation Tolerance MH - *Head and Neck Neoplasms MH - Cell Proliferation MH - Hypoxia-Inducible Factor 1, alpha Subunit PMC - PMC10313532 OTO - NOTNLM OT - Hypoxia OT - Laryngeal squamous cell carcinoma OT - Proliferation OT - Radiosensitivity OT - Tumour markers COIS- No competing interests and/or funding. EDAT- 2023/04/09 06:00 MHDA- 2023/07/03 06:41 PMCR- 2023/04/08 CRDT- 2023/04/08 11:13 PHST- 2022/12/20 00:00 [received] PHST- 2023/03/28 00:00 [accepted] PHST- 2023/07/03 06:41 [medline] PHST- 2023/04/09 06:00 [pubmed] PHST- 2023/04/08 11:13 [entrez] PHST- 2023/04/08 00:00 [pmc-release] AID - 10.1007/s00405-023-07951-9 [pii] AID - 7951 [pii] AID - 10.1007/s00405-023-07951-9 [doi] PST - ppublish SO - Eur Arch Otorhinolaryngol. 2023 Aug;280(8):3801-3809. doi: 10.1007/s00405-023-07951-9. Epub 2023 Apr 8.