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Insights into Fatty Acid Profiling and Prognostic Factors derived from FDG-PET/CT Imaging in Head and Neck Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.ORCID iD: 0000-0002-8347-7239
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. , p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2135
Keywords [en]
head and neck cancer, fatty acids, FDG-PET/CT, oropharyngeal cancer, malnutrition, inflammation, visceral adipose tissue, bone marrow
National Category
Cancer and Oncology
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-552477ISBN: 978-91-513-2427-2 (print)OAI: oai:DiVA.org:uu-552477DiVA, id: diva2:1944701
Public defence
2025-05-08, Skoogssalen, Akademiska sjukhuset, Ingång 78-79, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2025-04-16 Created: 2025-03-14 Last updated: 2025-04-16
List of papers
1. Circulating fatty acids in patients with head and neck cancer after treatment: an explorative study with a one-year perspective
Open this publication in new window or tab >>Circulating fatty acids in patients with head and neck cancer after treatment: an explorative study with a one-year perspective
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2021 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 141, no 9, p. 878-884Article in journal (Refereed) Published
Abstract [en]

Background: Unintended weight loss and nutritional problems are often seen in patients with head and neck cancer, but changes in lipid metabolism are poorly studied.

Aim/Objectives: The present study aimed to explore the longitudinal changes in circulating fatty acid (FA) composition in patients with head and neck cancer.

Materials and Methods: This study included 27 patients with head and neck cancer. Treatment consisted of single modality or combined modality treatments. The patients were assessed by repeated blood sampling and body weight assessments before treatment started and on three occasions after the start of treatment. FA profiling included gas chromatography analysis of unsaturated FAs and saturated FAs in serum.

Results: The values of three fatty acids - FA 14:0, FA 18:3n3, and FA 20:3n6 - changed in a specific pattern over the course of the study and the change in FA 14:0 correlated with weight changes.

Conclusions and significance: This study showed altered profiles of both saturated and unsaturated FAs. An improved understanding of the metabolic pathways in patients with head and neck cancer supports the development of better nutritional surveillance and nutritional treatments.

Place, publisher, year, edition, pages
Taylor & FrancisInforma UK Limited, 2021
Keywords
Fatty acids, chemoradiotherapy, head and neck cancer, nutrition, radiotherapy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-462870 (URN)10.1080/00016489.2021.1959950 (DOI)000685013800001 ()34392790 (PubMedID)
Funder
Swedish Cancer Society, 2015/363Swedish Cancer Society, 2018/502The Kamprad Family Foundation, 20150003
Available from: 2022-01-03 Created: 2022-01-03 Last updated: 2025-03-14Bibliographically approved
2. Longitudinal Changes in the Fatty Acid Profile in Patients with Head and Neck Cancer: Associations with Treatment and Inflammatory Response
Open this publication in new window or tab >>Longitudinal Changes in the Fatty Acid Profile in Patients with Head and Neck Cancer: Associations with Treatment and Inflammatory Response
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2022 (English)In: Cancers, ISSN 2072-6694, Vol. 14, no 15, article id 3696Article in journal (Refereed) Published
Abstract [en]

Simple Summary Cancer-associated malnutrition affects nutrient metabolism, including the metabolism of lipids. Toxicities associated with the treatment for head and neck cancer (HNC) may contribute to malnutrition through impaired oral intake and inflammation. Studies on lipid metabolism in patients with HNC are very limited. The anti-inflammatory effect of some fatty acids (FAs) is already proven in other cancers but the results of these studies in HNC are not consistent. This prospective study of 174 patients with HNC contributes to our knowledge of alterations in lipid metabolism following treatment for HNC and serves as basis for future research. Studies on fatty acids (FAs) in patients with head and neck cancer (HNC) are limited. We aimed to investigate the longitudinal changes of circulating FAs in patients with HNC and to examine potential correlations of FA changes with treatment. The secondary aims were to investigate correlations of FAs with cytokines and patient-related factors, and if any FAs correlated with disease recurrence or death. A total of 174 patients with HNC were included before treatment and followed-up at three time points after the start of the treatment through blood sampling and body weight measurements. Serum FA profiling was assessed by gas chromatography. The total follow-up time was 3 years. The levels of almost all FAs changed from baseline to 7 weeks. The change in FA 14:0 was associated with treatment and the change in 18:3n-6 was associated with the patients' pre-treatment BMI. FAs 14:0 and 18:0 were correlated with weight changes from baseline to 7 weeks. IL-6 was correlated with three FAs at 7 weeks and with two FAs at 1 year. Patients with higher levels 20:5n-3 at 3 months had a higher risk of all-cause death within 3 years (HR 2.75, 95% CI 1.22-6.21). Treatment, inflammation, and weight loss contributed in a complex manner to the altered FA profile in the studied cohort. The association between IL-6 and FAs in patients with HNC is in line with earlier studies and suggests the opportunity for regulating inflammation in HNC patients through modulation of FAs.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
head and neck cancer, fatty acids, inflammation
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-482664 (URN)10.3390/cancers14153696 (DOI)000839015700001 ()35954360 (PubMedID)
Funder
Swedish Cancer Society, 2015/363Swedish Cancer Society, 2018/502The Kamprad Family Foundation, 20150003P.O. Zetterling Foundation
Available from: 2022-09-22 Created: 2022-09-22 Last updated: 2025-03-14Bibliographically approved
3. Prognostic value of bone marrow and tumor 18F‐FDG uptake on PET/CT in patients with oropharyngeal cancer and the interplay between inflammation and FDG uptake
Open this publication in new window or tab >>Prognostic value of bone marrow and tumor 18F‐FDG uptake on PET/CT in patients with oropharyngeal cancer and the interplay between inflammation and FDG uptake
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2024 (English)In: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 46, no 10, p. 2422-2431Article in journal (Refereed) Published
Abstract [en]

Aims

To examine the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) for disease recurrence and survival in patients with oropharyngeal squamous cell carcinoma (OP-SCC). The secondary aims were to evaluate the prognostic value of PET/CT parameters for the primary oropharyngeal tumor and total tumor burden, and to assess the correlation between FDG uptake variables and serum inflammatory markers.

Methods

This was an observational study of 91 patients with OP-SCC who underwent pretreatment FDG-PET/CT. The patients' blood samples were collected before treatment, and treatment was administered with the intention to cure. The median follow-up time was 40 months. The PET parameters measured were SUVmeanBM for the assessment of BM FDG uptake, SUVmean, SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) for the evaluation of primary oropharyngeal tumor and total tumor burden.

Blood samples were analyzed to determine each patient's white cell, red cell, and platelet cell counts, hemoglobin, and C-reactive protein level. In a subgroup of 33 patients, blood serum was analyzed to evaluate the expression of serum immune proteins using a proximity extension assay (Olink Proteomics).

Results

The univariate analysis revealed that SUVmeanBM and tumor-specific parameters (SUVmaxtumor, SUVmeantotal, SUVmaxtotal, MTVtotal, TLGtotal) were significantly associated with recurrence-free survival (RFS). After adjusting for age, sex, and stage only SUVmeanBM remained significantly associated with RFS. Spearman's correlation identified several correlations between PET parameters and inflammatory markers.

Conclusions

Our results show that several FDG-PET/CT parameters may have a prognostic value of treatment outcome in patients with OP-SCC. However, SUVmeanBM was the only independent PET parameter that showed a prognostic value for RFS in the study cohort. Moreover, the study findings might suggest an association between systemic inflammation and the metabolic activity in the BM.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-543016 (URN)10.1002/hed.27711 (DOI)001179805600001 ()2-s2.0-85186895942 (Scopus ID)
Funder
Swedish Cancer Society, 2015/363Swedish Cancer Society, 2018/502P.O. Zetterling Foundation
Available from: 2024-11-18 Created: 2024-11-18 Last updated: 2025-03-14Bibliographically approved
4. FDG PET/CT assessment of visceral adipose tissue in patients with oropharyngeal cancer
Open this publication in new window or tab >>FDG PET/CT assessment of visceral adipose tissue in patients with oropharyngeal cancer
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-552449 (URN)
Available from: 2025-03-14 Created: 2025-03-14 Last updated: 2025-03-14

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