Thyroid cancer and nonsteroidal anti-inflammatory drug use: a pooled analysis of patients older than 40 years of age

Background: Cyclooxygenase (COX-2) has been associated with tumor growth and metastasis in several cancers, including thyroid cancer. For this reason, several investigators have studied COX-2 inhibitors in preclinical models of thyroid cancer and found antineoplastic effects. Thus, the primary aim of this study was to assess if the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of thyroid cancer. A second aim of the study was to determine additional risk or protective factors for thyroid cancer. Methods: Three large prospective population-based studies (the NIH-AARP Diet and Health Study; the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and the U.S. Radiologic Technologists Study) were pooled to investigate the association between self-reported frequency of aspirin and nonaspirin NSAID use one year prior to baseline (no use, ≤2/week, >2–6/week, and ≥7/week) and subsequent risk of thyroid cancer. A Cox regression proportional hazard model was used to estimate aggregated hazard ratios (HR) adjusted for cohort, sex, race/ethnicity, weight, smoking status, and alcohol intake. Results: There were 388,577 participants in the pooled cohort, with 481 cases of thyroid cancer. No significant risk reduction was observed with regular use of nonaspirin NSAIDs (HR = 1.14 [confidence interval (CI) 0.84–1.55]), and/or regular use of aspirin (HR = 1.06 [CI 0.82–1.39]). The multivariate regression analysis confirmed as previously reported in the literature that female sex, obesity class I (body mass index [BMI] = 30–34.99 kg/m(2)), and obesity class II (BMI = 35–35.99 kg/m(2)) were independently associated with an increased thyroid cancer risk. Current smoking status and moderate and excessive alcohol use were also confirmed as independent risk factors associated with a reduced thyroid cancer risk. Conclusions: Neither nonaspirin NSAIDs nor aspirin use is associated with a reduced risk of thyroid cancer. Women and obesity are associated with an increased risk of thyroid cancer, whereas smoking and alcohol use are associated with decreased risk of thyroid cancer

Management recommendations for pancreatic manifestations of von Hippel–Lindau disease

Von Hippel–Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018-2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL-related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility of biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL-related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL-related pancreatic manifestations

Prognosis after surgery for multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: Functionality matters

Background: Metastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis. Methods: Patients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival. Results: Out of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P = .001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%–76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%–91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47–6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22–7.33]) and World Health Organization grade 2 (2.95 [1.02–8.50]) were associated with liver metastases-free survival. Conclusion: Patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade

Multi-omics Signatures and Translational Potential to Improve Thyroid Cancer Patient Outcome

Recent advances in high-throughput molecular and multi-omics technologies have improved our understanding of the molecular changes associated with thyroid cancer initiation and progression. The translation into clinical use based on molecular profiling of thyroid tumors has allowed a significant improvement in patient risk stratification and in the identification of targeted therapies, and thereby better personalized disease management and outcome. This review compiles the following: (1) the major molecular alterations of the genome, epigenome, transcriptome, proteome, and metabolome found in all subtypes of thyroid cancer, thus demonstrating the complexity of these tumors and (2) the great translational potential of multi-omics studies to improve patient outcome

Bridging the Scientific Gaps to Identify Effective Treatments in Adrenocortical Cancer

Adrenocortical cancer (ACC) typically presents in advanced stages of disease and has a dismal prognosis. One of the foremost reasons for this is the lack of available systemic therapies, with mitotane remaining the backbone of treatment since its discovery in the 1960s, despite underwhelming efficacy. Surgery remains the only potentially curative option, but about half of patients will recur post-operatively, often with metastatic disease. Other local treatment options have been attempted but are only used practically on a case-by-case basis. Over the past few decades there have been significant advances in understanding the molecular background of ACC, but this has not yet translated to better treatment options. Attempts at novel treatment strategies have not provided significant clinical benefit. This paper reviews our current treatment options and molecular understanding of ACC and the reasons why a successful treatment has remained elusive. Additionally, we discuss the knowledge gaps that need to be overcome to bring us closer to successful treatment and ways to bridge them

Advances in Biomarker-Driven Targeted Therapies in Thyroid Cancer

Thyroid cancer is the most common type of endocrine malignancy comprising 2–3% of all cancers, with a constant rise in the incidence rate. The standard first-line treatments for thyroid cancer include surgery and radioactive iodine ablation, and a majority of patients show a good response to these therapies. Despite a better response and outcome, approximately twenty percent of patients develop disease recurrence and distant metastasis. With improved knowledge of molecular dysregulation and biological characteristics of thyroid cancer, the development of new treatment strategies comprising novel targets has accelerated. Biomarker-driven targeted therapies have now emerged as a trend for personalized treatments in patients with advanced cancers, and several multiple receptor kinase inhibitors have entered clinical trials (phase I/II/III) to evaluate their safety and efficacy. Most extensively investigated and clinically approved targeted therapies in thyroid cancer include the tyrosine receptor kinase inhibitors that target antiangiogenic markers, BRAF mutation, PI3K/AKT, and MAPK pathway components. In this review, we focus on the current advances in targeted mono- and combination therapies for various types of thyroid cancer

Markers of Systemic Inflammatory Response are Prognostic Factors in Patients with Pancreatic Neuroendocrine Tumors (PNETs): A Prospective Analysis.

The prognosis and behavior of pancreatic neuroendocrine tumors (PNETs) vary and may be divergent even at the same stage or tumor grade. Markers of systemic inflammatory response are readily available and are inexpensive, and have been shown to be prognostic factors in several cancers