Distant Metastases From Childhood Differentiated Thyroid Carcinoma:Clinical Course and Mutational Landscape

Context: Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. Objective: This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. Methods: A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age Results: We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). Conclusion: Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC

The Clinical Impact of [68Ga]‐DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone – Secreting Tumours

ObjectivesLocalization of ectopic ACTH‐secreting tumours causing Cushing syndrome (ECS) is essential for clinical management, yet often difficult. [68Ga]‐DOTATATE PET/CT ([68Ga]‐DOTA‐(Tyr3)‐octreotate)] is an FDA‐approved high‐resolution diagnostic tool for imaging neuroendocrine tumours. Data on the clinical utility of [68Ga]‐DOTATATE in patients with ECS, however, are scarce. The objectives of this study were to determine the efficacy for ECS localization and the clinical benefit of [68Ga]‐DOTATATE imaging.MethodWe conducted a retrospective review of all cases with ECS evaluated with [68Ga]‐DOTATATE from November 2016 through October 2018 at three referral centres. The clinical benefit of [68Ga]‐DOTATATE was based on detection of new tumours and resultant changes in management.ResultsOver the study period, 28 patients with ECS underwent [68Ga]‐DOTATATE: 17 for identification of the primary tumour and 11 during follow‐up. [68Ga]‐DOTATATE identified the suspected primary ECS in 11/17 patients (65%). Of these, nine patients underwent surgery: eight with confirmed ECS (5 bronchial, 1 thymic, 1 pancreatic and 1 metastatic neuroendocrine tumour of unknown primary origin) and one patient with a false‐positive scan (adrenal gland). Of the 11 patients with ECS who underwent [68Ga]‐DOTATATE evaluation during follow‐up, the study led to changes in clinical management in 7/11 (64%) patients.Conclusions[68Ga]‐DOTATATE is sensitive in detecting primary and metastatic ECS, often identifies occult tumours after conventional imaging, and impacts clinical care in the majority of patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150507/1/cen14008.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150507/2/cen14008_am.pd

Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma

The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association

Toward High Performance Computing Education

High Performance Computing (HPC) is the ability to process data and perform complex calculations at extremely high speeds. Current HPC platforms can achieve calculations on the order of quadrillions of calculations per second with quintillions on the horizon. The past three decades witnessed a vast increase in the use of HPC across different scientific, engineering and business communities, for example, sequencing the genome, predicting climate changes, designing modern aerodynamics, or establishing customer preferences. Although HPC has been well incorporated into science curricula such as bioinformatics, the same cannot be said for most computing programs. This working group will explore how HPC can make inroads into computer science education, from the undergraduate to postgraduate levels. The group will address research questions designed to investigate topics such as identifying and handling barriers that inhibit the adoption of HPC in educational environments, how to incorporate HPC into various curricula, and how HPC can be leveraged to enhance applied critical thinking and problem solving skills. Four deliverables include: (1) a catalog of core HPC educational concepts, (2) HPC curricula for contemporary computing needs, such as in artificial intelligence, cyberanalytics, data science and engineering, or internet of things, (3) possible infrastructures for implementing HPC coursework, and (4) HPC-related feedback to the CC2020 project

Recent advances in the management of hyponatremia in cancer patients

Hyponatremia is the most frequently encountered electrolyte disorder in cancer patients and is usually multifactorial in its origin. In this review, we discuss the predisposing factors, pathophysiology, clinical symptomatology, and currently available diagnostic and therapeutic options for the management of hyponatremia. In addition to paraneoplastic syndromes, concurrent chemotherapy and comorbidities predispose oncology patients to the risk of hyponatremia. Initial symptoms and signs can be subtle and the prompt evaluation and initiation of treatment is of paramount importance to prevent neurocognitive and other complications. The syndrome of inappropriate antidiuresis (SIAD) is the most common cause of hyponatremia, and the use of serum and urine parameters that distinguish SIAD from other etiologies is discussed. Individualized treatment is preferred depending on the underlying cause and severity of hyponatremia. The treatment of hyponatremia is reviewed and the importance of avoiding rapid overcorrection of the sodium level to reduce the risk of osmotic demyelination syndrome is emphasized. Vasopressin receptor antagonists (vaptans) offer a direct approach to the management of euvolemic and hypervolemic hyponatremia, but the indications for their use and long-term safety need to be clarified. The treatment of hyponatremia is likely to reduce complications and improve survival in cancer patients

Recent Therapeutic Advances in Pituitary Carcinoma

Pituitary carcinoma (PC) is a rare, aggressive malignancy that comprises 0.1–0.2% of all pituitary tumors. PC is defined anatomically as a pituitary tumor that metastasizes outside the primary intrasellar location as noncontiguous lesions in the central nervous system or as metastases to other organs. Similar to pituitary adenoma, PC originates from various cell types of the pituitary gland and can be functioning or nonfunctioning, with the former constituting the majority of the cases. Compression of intricate skull-based structures, excessive hormonal secretion, impaired pituitary function from therapy, and systemic metastases lead to debilitating symptoms and a poor survival outcome in most cases. PC frequently recurs despite multimodality treatments, including surgical resection, radiotherapy, and biochemical and cytotoxic treatments. There is an unmet need to better understand the pathogenesis and molecular characterization of PC to improve therapeutic strategies. As our understanding of the role of signaling pathways in the tumorigenesis of and malignant transformation of PC evolves, efforts have focused on targeted therapy. In addition, recent advances in the use of immune checkpoint inhibitors to treat various solid cancers have led to an interest in exploring the role of immunotherapy for the treatment of aggressive refractory pituitary tumors. Here, we review our current understanding of the pathogenesis, molecular characterization, and treatment of PC. Particular attention is given to emerging treatment options, including targeted therapy, immunotherapy, and peptide receptor radionuclide therapy

Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid cancer: the M. D. Anderson experience.

OBJECTIVES: Until recently, treatment options for patients with progressive, radioactive iodine-resistant differentiated thyroid cancer (DTC) have been limited. In our clinical practice, we have begun to use sorafenib and sunitinib for patients with progressive DTC who are not able or willing to participate in clinical trials. In this paper, we describe the University of Texas M. D. Anderson Cancer Center\u27s experience with the off-label use of these tyrosine kinase inhibitors for DTC. METHODS: Adult patients were included if they had a diagnosis of radioactive iodine-refractory DTC, were treated with single agent sorafenib or sunitinib, and had both baseline and at least one follow-up scan for restaging purposes. All imaging data were collected, as well as the TSH-suppressed thyroglobulin (Tg) levels corresponding to each scan date. The primary endpoints were radiographic response and progression-free survival (PFS). Secondary objectives were tissue-specific radiographic responses and correlation of Tg with overall response. RESULTS: We identified 33 patients from our clinical database. Fifteen patients (nine women, six men) met inclusion criteria, with a median age of 61 yr (range, 38-83 yr). Eight patients had papillary and seven had follicular thyroid carcinoma. Sorafenib was used in 13 and sunitinib in two, including one patient who failed prior sorafenib therapy. All patients had evidence of progressive disease (PD) before start of therapy, with a median PFS of only 4 months. Best response in target lesions was: partial response (PR) in three (20%), stable disease (SD) in nine (60%), and PD in three (20%). Clinical benefit (PR+SD) was 80%. The sunitinib patient previously refractory to sorafenib had a 38% reduction in tumor size. The most noticeable organ-specific response was observed in lung (median change, -22%) compared to lymph nodes (median change, 0%). Pleural disease and nonirradiated bone metastases demonstrated PD. All histological subtypes had similar responses. The median PFS was 19 months. The median overall survival has not yet been reached, but at 2 yr of follow-up, overall survival is 67%. Log Tg correlated with radiographic response (P = 0.0005). CONCLUSIONS: Sorafenib and sunitinib appear to be effective in patients with widely metastatic, progressive DTC, with most patients achieving SD or PR, despite having PD at baseline. The most noticeable responses occurred in the lungs in contrast with minimal changes in nodal metastases and PD in pleural and nonirradiated bone metastases, suggesting a tissue-specific response to therapy. Log Tg significantly correlated with response to treatment and therefore may have value as a surrogate marker of response