Novel concepts in imaging & treatment of thyroid tumors

Abstract

This thesis encompasses studies concerning the imaging and treatment of thyroid tumors including differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). Within these studies, innovation, de-escalation and personalized care are recurrent themes. A summary of this thesis is provided below. The systematic review in chapter 2 provides an overview of the current sentinel lymph node (SLN) techniques used for thyroid carcinoma. Multiple techniques for SLN procedure in thyroid carcinoma are feasible and accurate. The optimal execution consists of preoperative imaging with limited shine through effect, combined with an intraoperative identification method. In chapter 3 and 4, the rationale and results of a proof-of-concept study investigating the feasibility and effectiveness of the SLN procedure using 68Ga-tilmanocept PET/CT and ICG-99mTc-nanocolloid are shown. The procedure is effective and has the potential to personalize treatment of thyroid cancer according to nodal status. Chapter 5 contains a systematic review analysis and meta-analysis comparing the 8 most used minimally invasive techniques to open thyroidectomy. Minimally invasive techniques are not inferior to open thyroidectomy in terms of complications and hospital stay, and are therefore a safe alternative with the advantage of avoiding a potentially disfiguring scar in the neck. The usefulness of FDG PET/CT as first line nuclear imaging modality in patients suspected of persistent or recurrent DTC without first performing RAI WBS is examined in chapter 6. FDG PET/CT seems an accurate first line diagnostic nuclear imaging modality with a high positive predictive value for patients with detectable Tg after treatment during follow-up of DTC. In chapter 7, 68Ga-PSMA PET/CT imaging and the response to 177Lu-PSMA-617 therapy in patients with RAI refractory DTC is evaluated. 68Ga-PSMA PET/CT is able to detect various types of lesions in RAI refractory DTC, can detect additional lesions to 18FDG PET/CT and might be used to select patients for 177Lu-PSMA-617. One patient showed slight, temporary response after 177Lu-PSMA-617 therapy. The incidence, clinical significance and associated management strategies of incidentalomas found on PSMA PET/CT are addressed in chapter 8. Thyroid incidentalomas were found in 1.1% of patients. Less than half of found incidentalomas were further analyzed. Although low, the risk of malignancy, was not negligible. Chapter 9 shows that the theranostic target SSTR2A could serve as a prognostic factor for MTC patients, correlating with longer overall survival, particularly for stage IV. The uniform distribution within the tumor in most cases suggests the potential preoperative assessment of SSTR2A status using core needle or fine needle aspiration biopsies. However, the SSTR2A status in the primary MTC poorly predicts the expression in lymph node metastases. The study in chapter 10 evaluates the expression of αvβ3 in MTC and the corresponding lymph node metastases to assess its suitability as a theranostic target. Avβ3 is predominantly expressed in the cytoplasm and less in the membranes of MTC. This is unfortunate as the membranous expression is presumably most relevant for theranostic use.