Immunohistochemistry-based hypoxia-immune prognostic classifier for head-and-neck cancer patients undergoing chemoradiation - Post-hoc analysis from a prospective imaging trial.

Abstract

PURPOSE:

As both tumor hypoxia and an immunosuppressing tumor microenvironment hamper the anti-tumor activity of radiotherapy in head-and-neck squamous cell carcinoma (HNSCC), we aimed to develop an immunohistochemistry-based hypoxia-immune classifier.

METHODS:

39 patients receiving definitive chemoradiation for HNSCC within a prospective trial were included in this analysis. Baseline tumor samples were analyzed for the hypoxia marker carbonic anhydrase IX (CAIX) and tumor-infiltrating lymphocytes (TILs) and were correlated with [18F]-misonidazole ([18F]FMISO) PET measurements. The impact of the biomarkers on the locoregional control (LRC) was examined using Cox analyses and concordance index statistics.

RESULTS:

Low CAIX (HR = 0.352, 95%CI 0.124-1.001, p = 0.050) and high TIL levels (HR = 0.308, 95%CI 0.114-0.828, p = 0.020) were independent parameters for improved LRC and did not correlate with each other (Spearman's ρ = 0.034, p = 0.846). Harrell's C was 0.66 for CAIX and TIL levels alone and 0.71 for the combination. 2-year LRC was 73%, 62% and 11% for the prognostically good (CAIXlow/TILhigh), intermediate (CAIXlow/TILlow or CAIXhigh/TILhigh) and poor groups (CAIXhigh/TILlow), respectively (p = 0.001). Focusing on T lymphocytes, the hypoxia-immune classifier could still stratify between favorable (CAIXlow/CD3 + TILhigh), intermediate (CAIXlow/CD3 + TILlow or CAIXhigh/CD3 + TILhigh) and poor subgroups (CAIXhigh/CD3 + TILlow) with a 2-year LRC of 80%, 59% and 14%, respectively (p = 0.001). There was a positive correlation between baseline CAIX levels and [18F]FMISO SUV in week 2 of chemoradiation (ρ = 0.324, p = 0.050), indicating an association between higher baseline CAIX expression and tumor hypoxia persistence.

CONCLUSION:

We developed a clinically feasible hypoxia-immune prognostic classifier for HNSCC patients based on pre-treatment immunohistochemistry. However, external validation is required to determine the prognostic value and the potential usage for personalized radiation oncology.

• Authors: Alexander Rühle, Anca-L Grosu, Nicole Wiedenmann, Raluca Stoian, Erik Haehl, Constantinos Zamboglou, Dimos Baltas, Martin Werner, Gian Kayser, Nils H Nicolay
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 159 Pg. 75-81 (06 2021) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 33753155 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Carbonic Anhydrase IX

Topics

• Biomarkers, Tumor
• Carbonic Anhydrase IX
• Head and Neck Neoplasms (diagnostic imaging, therapy)
• Humans
• Hypoxia
• Immunohistochemistry
• Positron-Emission Tomography
• Prognosis
• Prospective Studies
• Tumor Microenvironment