Repeat FMISO-PET imaging weakly correlates with hypoxia-associated gene expressions for locally advanced HNSCC treated by primary radiochemotherapy

Radiother Oncol. 2019 Jun:135:43-50. doi: 10.1016/j.radonc.2019.02.020. Epub 2019 Mar 9.

Abstract

Background: Hypoxia is an important factor of tumour resistance to radiotherapy, chemotherapy and potentially immunotherapy. It can be measured e.g. by positron emission tomography (PET) imaging or hypoxia-associated gene expressions from tumour biopsies. Here we correlate [18F]fluoromisonidazole (FMISO)-PET/CT imaging with hypoxia-associated gene expressions on a cohort of 50 head and neck squamous cell carcinoma (HNSCC) patients and compare their prognostic value for response to radiochemotherapy (RCTx).

Methods: FMISO-PET/CT images of 50 HNSCC patients were acquired at four time-points before and during RCTx. For 42 of these patients, hypoxia-associated gene expressions were evaluated by nanoString technology based on a biopsy obtained before any treatment. The FMISO-PET parameters tumour-to-background ratio and hypoxic volume were correlated to the expressions of 58 hypoxia-associated genes using the Spearman correlation coefficient ρ. Three hypoxia-associated gene signatures were compared regarding their correlation with the FMISO-PET parameters using their median expression. In addition, the correlation with tumour volume was analysed. The impact of both hypoxia measurement methods on loco-regional tumour control (LRC) and overall survival (OS) was assessed by Cox regression.

Results: The median expression of hypoxia-associated genes was weakly correlated to hypoxia measured by FMISO-PET imaging (ρ ≤ 0.43), with higher correlations to imaging after weeks 1 and 2 of treatment (p < 0.001). Moderate correlations were obtained between FMISO-PET imaging and tumour volume (ρ ≤ 0.69). Prognostic models for LRC and OS based on the FMISO-PET parameters could not be improved by including hypoxia classifiers.

Conclusion: We observed low correlations between hypoxia FMISO-PET parameters and expressions of hypoxia-associated genes. Since FMISO-PET showed a superior patient stratification, it may be the preferred biomarker over hypoxia-associated genes for stratifying patients with locally advanced HNSCC treated by primary RCTx.

Keywords: FMISO-PET; Gene signature; Hypoxia; Locally advanced HNSCC; Radiochemotherapy.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / genetics*
  • Cell Hypoxia / radiation effects
  • Cohort Studies
  • Female
  • Fluorine Radioisotopes
  • Gene Expression / drug effects
  • Gene Expression / radiation effects
  • Head and Neck Neoplasms / diagnostic imaging*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Misonidazole / analogs & derivatives
  • Positron Emission Tomography Computed Tomography / methods
  • Prognosis
  • Radiopharmaceuticals
  • Squamous Cell Carcinoma of Head and Neck / diagnostic imaging*
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / therapy*
  • Tumor Burden

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • fluoromisonidazole
  • Misonidazole