Personalized management of differentiated thyroid cancer: Implications for de-escalation in clinical pathways

Following advancements in diagnostic imaging and its widespread use, there has been an increase in the detection of differentiated thyroid cancers (DTC), contributing to the rising incidence of this disease. The increasing incidence of early-stage thyroid tumors with a favorable prognosis raises questions about the necessity of traditional oncological treatment approaches for all cases of DTC. Scientific research in various types of cancer with positive oncological outcomes has shifted towards exploring treatment omission without compromising safety and preserving quality of life. These trends towards a refined treatment de-escalation reflect better risk stratification in cancer care indicating that some cancers can be treated conservatively. Considering the excellent survival rates of DTC, it is worth exploring de-escalation strategies. International guidelines have been evolving to incorporate higher thresholds for thyroid cancer therapy. However, variations in clinical practice patterns exist due to discrepancies among guidelines and a lack of literature on the role of active surveillance in low-risk thyroid cancer. In this thesis, we evaluate the current clinical challenges in the management of thyroid cancer patients, focusing on incidental thyroid nodules, second primary thyroid malignancies, and thyroid cancer in adolescents and young adults. The first part of this thesis focuses on the unintended uptake of radioactive agents 18F-FDG and PSMA in the thyroid during PET/CT scans in oncological patients, known as thyroid incidentalomas. We investigated that the definition of a PSMA thyroid incidentaloma can be reliably limited to focal uptake with a SUVmax thyroid/bloodpool ratio of ≥ 2.0. We also showed that one combined radiomics feature, the Run Length Non-Uniformity, derived from the 18F-FDG PET/CT scan demonstrates a comparable diagnostic value to the TIRADS classification to classify thyroid incidentalomas. The clinical outcomes of thyroid incidentalomas in our studies were favorable despite a minority of patients undergoing additional diagnostic procedures. Active treatment of thyroid incidentalomas may provide benefits to a subset of patients with either cured or stable underlying cancer. In part two, the association of differentiated thyroid cancer with other cancer types and the clinical management of thyroid cancer in adolescents and young adults were evaluated. Patients with breast cancer had a higher risk of developing differentiated thyroid cancer as a second primary malignancy and vice versa compared to the general population. The overall survival of these patients was comparable to those with primary breast- or differentiated thyroid cancer. An elevated risk of differentiated thyroid cancer in adolescent and young adult patients treated for Hodgkin’s disease was also observed compared to the general population. A history of Hodgkin's disease during adolescence and young adulthood can be considered a risk factor for metastatic differentiated thyroid cancer based on our study results. The overall survival of these patients was comparable to those with primary differentiated thyroid cancer. Lastly, we reviewed that radioactive iodine, administered to many young women with thyroid cancer, can cause menstrual irregularities in the first year without a significant decrease in pregnancy rates