Constantina Nadia Christou: Insights into Fatty Acid Profiling and Prognostic Factors derived from FDG-PET/CT Imaging in Head and Neck Cancer

Abstract

The progression towards personalized treatment strategies in Head and Neck Cancer (HNC) necessitates the identification of novel tumor- and host-specific prognostic factors. Malnutrition assocciated with HNC and its treatments significantly impacts metabolic processes, including lipid metabolism. This thesis aims to investigate various prognostic factors obtained from blood and 18F-Fluorodeoxyglucose (FDG) PET/CT imaging, as well as metabolic factors, in HNC.

The primary objectives of Studies I and II were to assess the longitudital alterations in circulating fatty acids (FAs) among patients with HNC and to evaluate potential correlations between these FA changes, treatment regimens, and inflammation. The cohort of study I comprised 27 patients with HNC, with a study design that was replicated in study II. Blood samples and body weight measurements were collected prior to tretamnet and at three intervals following treatment. Specific changes were observed in the levels of saturated FA 14:0 and two unsaturated FAs, 18:3n-3 and 20:3n-6. The modifications in the levels of 14:0 were correlated with the changes in body weight.

In study II, the cohort was expanded to encompass a total of 174 patients. In addition to gas chromatography analyses for FAs, the study incorporated the evaluation of four cytokines. The results indicated significant alterations in the levels of nearly all FAs from pre-treatment to the 7-week mark. Furthermore, interleukin-6 (IL-6) was associated with three FAs at 7 weeks, and with two other FAs at 1-year. Patients with elevated levels of 20:5n-3 at the 3-months assessment exhibited an increased risk of all-cause death within a 3-year period.

Study III involved 91 patients with oropharyngeal squamous cell carcinoma (OPSCC), examined with FDG-PET/CT before treatment. The PET parameters assessed included FDG uptake in the bone marrow (SUVmeanBM) and tumor-related FDG uptake. Pretreatment blood samples were analyzed for inflammatory markers. A subgroup of 33 patients underwent additional analysis of serum immune proteins. Several PET parameters exhibited prognostic value for recurrence-free survival (RFS). However, SUVmeanBM emerged as the sole independent prognostic PET parameter. Correlations were identified between PET parameters and inflammatory markers.

The objective of study IV was to evaluate the prognostic significance of various measurements of visceral adipose tissue (VAT) derived from pre-treatmet FDG-PET/CT in 82 patients with OPSCC. Blood samples, body mass index, and bioimpedance measurements were obtained before treatment. Findings indicated that higher CT attenuation (CT_HU) of VAT and higher SUVmeanVAT were associated with incerased risk of recurrence and/or death. Among patients with p-16 positive OPSCC, a non-significant association was observed between SUVmeanVAT and RFS. A strong correlation was noted between SUVmeanVAT and CT_HU.

The findings presented in this thesis provide a foundation for future investigations into metabolism in HNC and its clinical significance in medical practice. Furthermore, the thesis highlights the potential to expand the use of FDG-PET/CT in the search for prognostic markers and paves the way for the introduction of novel PET tracers in HNC, with both clinical and scientific applications.