Thyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status.... Show moreThyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status. These advanced radioactive iodine-refractory thyroid cancer patients often have an aggressive disease course and poor prognosis. Unfortunately, no good treatment options are available for these patients.The registered drugs for this purpose include molecularly targeted therapy with the tyrosine kinase inhibitors (TKIs) lenvatinib, sorafenib, and as second-line cabozantinib. These agents were shown to delay progressive disease in clinical trials, but not overall survival. Moreover, the setting of a clinical trial is often stricter than real-life, as reflected by less favorable outcomes in real-world data. Furthermore, these drugs frequently have (intolerable) adverse events. When the limited treatment options for refractory thyroid cancer have been exhausted, inclusion in clinical trials is often recommended by international guidelines.More recent ‘basket trials’ also study tumor type-agnostic prescription of drugs based on molecular tumor profiling; e.g. an ALK TKI in presence of an ALK gene fusion. The molecular characterization of neoplasms may also improve diagnosis and/or help direct the further management strategy; e.g. in indeterminate thyroid cytopathology, or in specific cases of Multi-UniFocality in contrast to multifocality. Show less
Multi-instance learning, a commonly used technique in artificial intelligence for analyzing slides, can be applied to diagnose thyroid cancer based on cytological smears. Since smears do not have... Show moreMulti-instance learning, a commonly used technique in artificial intelligence for analyzing slides, can be applied to diagnose thyroid cancer based on cytological smears. Since smears do not have mul-tidimensional histological features similar to histopathology, mining potential contextual information and diversity of features is crucial for better classification performance. In this paper, we propose a pyramid multi-loss vision transformer model called PyMLViT, a novel algorithm with two core modules to address these issues. Specifically, we design a pyramid token extraction module to acquire potential contextual information on smears. The pyramid token structure extracts multi-scale local features, and the vision transformer structure further obtains global information through the self -attention mechanism. Furthermore, we construct multi-loss fusion module based on the conventional multi-instance learning framework. With carefully designed bag and patch weight allocation strategies, we incorporate slide-level annotations as pseudo-labels for patches to participate in training, thus enhancing the diversity of supervised information. Extensive experimental results on the real-world dataset show that PyMLViT has a high performance and a competitive number of parameters compared to popular methods for diagnosing thyroid cancer in cytological smears.& COPY; 2023 Elsevier B.V. All rights reserved. Show less
Cameselle-Teijeiro, J.M.; Mete, O.; Asa, S.L.; LiVolsi, V. 2021
Cancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past... Show moreCancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past decade. However the incidence of familial disease has not been emphasized and is often overlooked in routine practice. A careful clinical documentation of family history or familial syndromes that can be associated with thyroid disease can help identify germline susceptibility-driven thyroid neoplasia. In this review, we summarize a large body of information about both syndromic and non-syndromic familial thyroid carcinomas. A significant number of patients with inherited non-medullary thyroid carcinomas manifest disease that appears to be sporadic disease even in some syndromic cases. The cytomorphology of the tumor(s), molecular immunohistochemistry, the findings in the non-tumorous thyroid parenchyma and other associated lesions may provide insight into the underlying syndromic disorder. However, the increasing evidence of familial predisposition to non-syndromic thyroid cancers is raising questions about the importance of genetics and epigenetics. What appears to be "sporadic" is becoming less often truly so and more often an opportunity to identify and understand novel genetic variants that underlie tumorigenesis. Pathologists must be aware of the unusual morphologic features that should prompt germline screening. Therefore, recognition of harbingers of specific germline susceptibility syndromes can assist in providing information to facilitate early detection to prevent aggressive disease. Show less
This thesis, describes investigations of the genetic background of a wide variety of rare endocrine tumors, including those of the thyroid, parathyroid, adrenal and paraganglia. In the first part,... Show moreThis thesis, describes investigations of the genetic background of a wide variety of rare endocrine tumors, including those of the thyroid, parathyroid, adrenal and paraganglia. In the first part, our studies focus on the role of molecular testing in diagnostics and treatment decision making in patients with DICER1 syndrome or advanced radioactive iodine refractory thyroid cancer. In the second part, we investigated the of genetic background of pediatric non-medullary thyroid carcinoma. In the third part we focused on genetic counseling in the following endocrine tumor predisposition syndromes: CDC73-related disorder, SDHA-associated paraganglioma and MEN2a syndrome. Our studies contributed to the debate on accurate estimation of disease penetrance. In order to provide answers to the questions - “Why do I have cancer? Are other relatives at risk? And if so, can we prevent cancer?” - patient- and family centered endocrine cancer care encourages active collaboration between the departments of endocrinology, oncology, surgery, pathology, chemistry, radiology, nuclear medicine and clinical genetics. Show less
In this thesis we describe the latest developments in the field of advanced thyroid cancer. Several clinical trials with sorafenib and everolimus were performed. The relation between clinical... Show moreIn this thesis we describe the latest developments in the field of advanced thyroid cancer. Several clinical trials with sorafenib and everolimus were performed. The relation between clinical outcome and mutational status was analyzed. Furthermore, the pharmacokinetics of everolimus in patients with advanced thyroid cancer was described. Show less
