University of Twente Student Theses
Multimodal imaging of the tumour microenvironment in head and neck cancer
Genugten, E.A.J. van (2020) Multimodal imaging of the tumour microenvironment in head and neck cancer.
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| Abstract: | Introduction: The five year survival of patients with head and neck squamous cell carcinomas (HNSCC) has remained unchanged in the last decade even though the morbidity due to treatment remains high. Currently, treatment decisions are based on clinical presentation whereas the increased therapy response in HPV induced oropharyngeal carcinomas (OPSCC) suggests a large influence of biological factors. Genetic mutations do not accurately represent the complexity of individual specialized cell types and extracellular matrix that is known as the tumour microenvironment. In order to become malignant, a tumour has to acquire multiple capabilities, in an early phase of tumourigenesis induction of angiogenesis is upregulated. Multimodal imaging is proposed to characterize angiogenesis using 68Ga-RGD2 PET/CT, designed to target angiogenesis-related integrin v 3, and perfusion of blood within tumour and possible suspected lymph nodes by CT perfusion. Previous dynamic PET imaging results of HNSCC patients intravenously injected with 68Ga-RGD2 concluded a steady state in tumour uptake and good tumour to background signal after 10 15min incubation. A phantom and patient test concluded feasibility of the newly developed oropharyngeal carcinoma CT perfusion protocol. Method: Ten patients with HPV+ and ten with HPV OPSCC scheduled for chemoradiotherapy are expected to be prospectively included in this clinical study. At the time of writing, one patient with a HPV+ T2N1M0 OPSCC was included. The subject underwent CT perfusion imaging and list mode PET/CT imaging from 10 to 20min after an intravenous injection of 68Ga-RGD2 (2136 81MBq) before commencement of therapy. During the second week of chemoradiotherapy, 68Ga-RGD2 PET/CT and CT perfusion scans were repeated (follow-up) to. MRI and [18F]FDG PET/CT made per standard of care were correlated to the study results an on basis of the MRI, tissues were characterized as benign or malignant. Quantitative analysis of the tumour, suspected lymph nodes and benign reference tissue was expressed as Standardized Uptake Values (SUV) for the 68Ga-RGD2 PET/CT scans from 15 to 20min post injection and for the [18F]FDG PET/CT scan. For these tissues, the arterial flow (AF), blood volume (BV) and flow extraction product (FE) were calculated on basis of the CT perfusion scan. Results: SUVmean and SUVmax of [18F]FDG within the tumour were 8.1 and 28.7, respectively, resulting in a total lesion glycolysis (TLG) of 117.5g. 68Ga-RGD2 uptake was increased during the follow-up scan (baseline SUVmax 8.7 and follow-up 12.1) as well as the FE, BV and AF decreased slightly. CT perfusion parameters, 68Ga-RGD2 and [18F]FDG uptake varied considerably for lymph nodes with and without central necrosis. AF, BV and 68Ga-RGD2 uptake was higher during follow-up in all suspected lymph nodes compared to baseline. A benign tooth abscess had high baseline characteristics comparable to necrotic lymph nodes, during the follow-up scan decrease in BV and 68Ga-RGD2 uptake was seen. Discussion & Conclusion: Possible positive correlations with response to therapy were found on basis of comparison of TLG, AF and BV to literature. However, the [18F]FDG SUVmax and baseline 68GaRGD2 SUVmean were comparable to uptake in HPV tumours which could indicate a worse prognosis. The difference in quantitative parameters between necrotic and non-necrotic lymph nodes is probably due to an accompanying inflammatory process. This is concluded on basis of pro-inflammatory signals that are shown to be released by necrotic cell death, the comparable values of a benign abscess and high [18F]FDG uptake that can be a hallmark of extracapsular spread of tumour. Increased uptake of 68GaRGD2, and therefore increased expression of integrin v 3, is seen in the tumour and suspected lymph nodes during the follow-up scan. An hypothesis is that this sustained angiogenesis reflects the adaptation of the carcinoma to the treatment resulting in persistence of a non-hypoxic tumour environment and therefore persevering response to chemoradiotherapy. Characterization of the tumour microenvironment with multimodal imaging could possibly help us in the future to identify targets for therapy and monitor response |
| Item Type: | Essay (Master) |
| Faculty: | TNW: Science and Technology |
| Subject: | 44 medicine |
| Programme: | Technical Medicine MSc (60033) |
| Link to this item: | https://purl.utwente.nl/essays/80774 |
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