Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139948/1/onco0165.pd

Marginal treatment benefit in anaplastic thyroid cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99665/1/cncr28187.pd

ADVERSE EVENTS IN LOW VERSUS NORMAL BODY WEIGHT PATIENTS PRESCRIBED APIXABAN OR RIVAROXABAN FOR ATRIAL FIBRILLATION

Background: Clinical trials comparing direct oral anticoagulants (DOACs) to warfarin included only a small number of patients that weighed less than 60 kilograms (kg). The safety and efficacy of DOACs in low weight adult patients with atrial fibrillation (AF) is still unclear. Published data is not only sparse but have mixed outcomes. Therapy with DOACs may increase bleeding and/or clotting risk with uncertain antithrombotic benefit in low weight patients. Objective: To assess bleeding and thrombotic event rates for patients with AF that are prescribed a DOAC and have a low body weight (less than 60 kg) versus patients that have a normal body weight (60 to 100 kg). Methods: Within the Michigan Anticoagulation Quality Improvement Initiative (MAQI2), we analyzed data for patients with AF prescribed apixaban or rivaroxaban from 2017 through 2021 who had at least 12 months of follow-up. Patients were excluded if they were prescribed dosing different from package insert instructions. Patients were divided by weight into low (less than 60 kg) and normal (60 to 100 kg) cohorts. Assessments included rates of thrombotic events, major bleeding events (International Society on Thrombosis and Haemostasis [ISTH]), and non-major bleeding events requiring an Emergency Department (ED) visit. Patient characteristics were compared using Chi-square and t-test. Bleeding event rates were adjusted for age, gender, and diabetes mellitus and thrombotic event rates were adjusted by CHA2DS2-VASc score. Poisson regression was used to estimate adjusted adverse event rates to control for potentially confounding covariates (apixaban only due to few patients prescribed rivaroxaban). Results: A total of 616 patients met the inclusion criteria: 83 (13.5%) low weight and 533 (86.5%) normal weight. Most patients were prescribed apixaban (88.5%) with the low weight cohort more often prescribed the lower dose of apixaban (55% versus 6.2%, p\u3c0.0001). The low weight cohort had a higher mean age (78.9% versus 74.4%, p\u3c0.0002), proportion of females (94% versus 54%, p\u3c0.0001) and CHA2DS2-VASc score (4.4 (1.6) versus 3.9 (1.6)), but a lower proportion of patients with diabetes mellitus (9.6% versus 25.1%, p\u3c0.0018) [Table 1]. In the unadjusted analysis of patients prescribed apixaban, non-major bleeding events requiring an ED visit (10.8 per 100 patient-years versus 7.4 per 100 patient-years, p\u3c0.0001), occurred more often in the low versus normal weight patient cohort [Table 2]. However, adjusted analysis found no statistically significant difference in events in low and normal weight cohorts prescribed apixaban [Table 2]. Comparisons within patients prescribed rivaroxaban could not be made due to a small sample size of low weight patients. Conclusions: Among low weight patients with AF the use of apixaban was not associated with bleeding (major and non-major) or thrombotic events after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients

Risk of Osteoporosis and Fractures in Patients with Thyroid Cancer: A Caseâ Control Study in U.S. Veterans

BackgroundData on osteoporosis and fractures in patients with thyroid cancer, especially men, are conflicting. Our objective was to determine osteoporosis and fracture risk in U.S. veterans with thyroid cancer.Materials and MethodsThis is a caseâ control study using the Veterans Health Administration Corporate Data Warehouse (2004â 2013). Patients with thyroid cancer (n = 10,370) and controls (n = 10,370) were matched by age, sex, weight, and steroid use. Generalized linear mixedâ effects regression model was used to compare the two groups in terms of osteoporosis and fracture risk. Next, subgroup analysis of the patients with thyroid cancer using longitudinal thyroidâ stimulating hormone (TSH) was performed to determine its effect on risk of osteoporosis and fractures. Other covariates included patient age, sex, median household income, comorbidities, and steroid and androgen use.ResultsCompared with controls, osteoporosis, but not fractures, was more frequent in patients with thyroid cancer (7.3% vs. 5.3%; odds ratio [OR], 1.33; 95% confidence interval [CI], 1.18â 1.49) when controlling for median household income, Charlson/Deyo comorbidity score, and androgen use. Subgroup analysis of patients with thyroid cancer demonstrated that lower TSH (OR, 0.93; 95% CI, 0.90â 0.97), female sex (OR, 4.24; 95% CI, 3.53â 5.10), older age (e.g., â ¥85 years: OR, 17.18; 95% CI, 11.12â 26.54 compared with <50 years), and androgen use (OR, 1.63; 95% CI, 1.18â 2.23) were associated with osteoporosis. Serum TSH was not associated with fractures (OR, 1.01; 95% CI, 0.96â 1.07).ConclusionOsteoporosis, but not fractures, was more common in U.S. veterans with thyroid cancer than controls. Multiple factors may be contributory, with low TSH playing a small role.Implications for PracticeData on osteoporosis and fragility fractures in patients with thyroid cancer, especially in men, are limited and conflicting. Because of excellent survival rates, the number of thyroid cancer survivors is growing and more individuals may experience longâ term effects from the cancer itself and its treatments, such as osteoporosis and fractures. The present study offers unique insight on the risk for osteoporosis and fractures in a largely male thyroid cancer cohort. Physicians who participate in the longâ term care of patients with thyroid cancer should take into consideration a variety of factors in addition to TSH level when considering risk for osteoporosis.Thyroid stimulating hormone suppression therapy may contribute to bone loss in patients with thyroid cancer, especially in postmenopausal women. The link between thyroid cancer treatment and osteoporosis and fractures in men is less certain. This article reports results of a study designed to address this knowledge gap.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151904/1/onco12999-sup-0002-Tables.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151904/2/onco12999-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151904/3/onco12999_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151904/4/onco12999.pd

Factors That Influence Radioactive Iodine Use for Thyroid Cancer

Background: There is variation in the use of radioactive iodine (RAI) as treatment for well-differentiated thyroid cancer. The factors involved in physician decision-making for RAI remain unknown. Methods: We surveyed physicians involved in postsurgical management of patients with thyroid cancer from 251 hospitals. Respondents were asked to rate the factors important in influencing whether a thyroid cancer patient receives RAI. Multivariable analyses controlling for physician age, gender, specialty, case volume, and whether they personally administer RAI, were performed to determine correlates of importance placed on patients' and physicians' worry about death from cancer and differences between low? versus higher?case-volume physicians. Results: The survey response rate was 63% (534/853). Extent of disease, adequacy of surgical resection, patients' willingness to receive RAI, and patients' age were the factors physicians were most likely to report as quite or very important in influencing recommendations for RAI to patients with thyroid cancer. Interestingly, both physicians' and patients' worry about death from thyroid cancer were also important in determining RAI use. Physicians with less thyroid cancer cases per year were more likely than higher-volume physicians to report patients' (p<0.001) and physicians' worry about death (p=0.016) as quite or very important in decision-making. Other factors more likely to be of greater importance in determining RAI use for physicians with lower thyroid cancer patient volume versus higher include the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI expressed by colleagues comanaging patients (p=0.003), and patient distance from the nearest facility administering RAI (p=0.012). Conclusion: In addition to the extent of disease and adequacy of surgical resection, physicians place importance on physician and patient worry about death from thyroid cancer when deciding whether to treat a patient with RAI. The factors important to physician decision-making differ based on physician thyroid-cancer case-volume, with worry about death being more influential for low?case-volume physicians. As the mortality from thyroid cancer is low, the importance placed on death in decision making may be unwarranted.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140258/1/thy.2012.0380.pd

Conditional Survival in Patients with Thyroid Cancer

Background: Thyroid cancer is an increasingly common malignancy. Although likelihood of survival from well-differentiated thyroid cancer can vary by disease severity, it is not known how patients' life expectancies change the farther they are from time of diagnosis. Methods: Using data from the Surveillance, Epidemiology, End Results (SEER) registry, we selected patients diagnosed with well-differentiated thyroid cancer (N=43,392) between 1998 and 2005. Patients were followed for up to 12 years. Conditional survival estimates by SEER stage and age were obtained based on Cox proportional hazards regression model of disease-specific survival. Results: Patients with localized thyroid cancer have excellent conditional 5-year survival, irrespective of where they are in their survivorship phase. Patients with regional thyroid cancer have relatively stable conditional 5-year survival, whereas for patients with distant thyroid cancer there is gradual improvement the farther from time of diagnosis. Age and gender influence conditional survival. Similarly, age has a strong effect on disease-specific survival for patients with thyroid cancer with localized (hazard ratio [HR] 88.7 [95% confidence interval {CI} 26.3?552), comparing age ≥80 with <30 years), regional (HR 105 [95% CI 52.6?250]), and distant disease [HR 86.8 (95% CI 32.5?354)]. Male gender is also associated with a significantly worse disease-specific survival among patients with regional disease (HR 1.56 [95% CI 1.31?1.85]) but not among patients with localized or distant disease. Conclusion: Cancer stage, gender, age at diagnosis, and length of time already survived can influence conditional survival for patients with thyroid cancer. Understanding the conditional 5-year disease-specific survival of well-differentiated thyroid cancer is key to creating treatment plans and tailoring surveillance.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140260/1/thy.2014.0264.pd

Evaluating Positron Emission Tomography Use in Differentiated Thyroid Cancer

Background: Using the Surveillance, Epidemiology, and End Results?Medicare database, a substantial increase was found in the use of positron emission tomography (PET) scans after 2004 in differentiated thyroid cancer (DTC) patients. The reason for the increased utilization of the PET scan was not clear based on available the data. Therefore, the indications for and outcomes of PET scans performed at an academic institution were evaluated. Methods: A retrospective cohort study was performed of DTC patients who underwent surgery at the University of Michigan Health System from 2006 to 2011. After identifying patients who underwent a PET scan, indications, rate of positive PET scans, and impact on management were evaluated. For positive scans, the location of disease was characterized, and presence of disease on other imaging was determined. Results: Of the 585 patients in the cohort, 111 (19%) patients had 200 PET scans performed for evaluation of DTC. Indications for PET scan included: elevated thyroglobulin and negative radioiodine scan in 52 scans (26.0%), thyroglobulin antibodies in 13 scans (6.5%), rising thyroglobulin in 18 scans (9.0%), evaluation of abnormality on other imaging in 22 scans (11.0%), evaluation of extent of disease in 33 scans (16.5%), follow-up of previous scan in 57 scans (28.5%), other indications in two scans (1.0%), and unclear indications in three scans (1.5%). The PET scan was positive in 124 studies (62.0%); positivity was identified in the thyroid bed on 25 scans, cervical or mediastinal lymph nodes on 105 scans, lung on 28 scans, bone on four scans, and other areas on 14 scans. Therapy following PET scan was surgery in 66 cases (33.0%), chemotherapy or radiation in 23 cases (11.5%), observation in 110 cases (55.0%), and palliative care in one case (0.5%). Disease was identifiable on other imaging in 66% of cases. PET scan results changed management in 59 cases (29.5%). Conclusions: In this academic medical center, the PET scan was utilized in 19% of patients. Indications for the PET scan included conventional indications, such as elevated thyroglobulin with noniodine avid disease, and more controversial uses, such as evaluation of extent of disease or abnormalities on other imaging tests. PET scan results changed management in about 30% of cases.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140264/1/thy.2015.0062.pd

The Most Commonly Occurring Papillary Thyroid Cancer in the United States Is Now a Microcarcinoma in a Patient Older than 45 Years

Background: The incidence of papillary thyroid cancer (PTC) is growing at a faster rate than any other malignancy. However, it is unknown what effect age is having on the changing PTC incidence rates. With the goal of understanding the role of age in thyroid cancer incidence, this study analyzes the changing demographics of patients with PTC over the past three decades. Methods: This was a retrospective evaluation of the incidence rates of PTC from 1973 to 2006 reported by the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Results: From 1973-2006 the age group most commonly found to have PTC has shifted from patients in their 30s to patients in the 40-50-year-old age group. In 1973 60% of PTC cases were found in patients younger than 45, and the majority of cases continued to occur in younger patients until 1999. After 1999 PTC became more common in patients older than 45 years, and in 2006, 61% of PTC cases were in patients older than 45 years. From 1988 to 2003 there has been an increasing incidence of all sizes of PTC in all age groups with the largest increase in tumors <1-cm in patients older than 45. Forty-three percent of tumors in patients older than 45 are now <1-cm, whereas only 34% are <1-cm in patients younger than 45. Of the nearly 20,000 thyroid cancer cases in 2003, 24% were microcarcinomas in patients over the age of 45. Conclusions: The incidence of PTC is increasing disproportionally in patients older than 45 years. The number of PTC tumors smaller than 1-cm is increasing in all age groups, and now the most commonly found PTC tumor in the United States is a microcarcinoma in a patient older than 45 years. These changing patterns relating age and incidence have important prognostic and treatment implications for patients with PTC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90466/1/thy-2E2010-2E0137.pd

The Relationship Between Imaging and Thyroid Cancer Diagnosis and Survival

BackgroundControversy exists over whether there has been a true increase in the occurrence of thyroid cancer or overdiagnosis secondary to imaging practices. Because cancer overdiagnosis is associated with detection of indolent disease, overdiagnosis can be associated with perceived improvement in survival.Materials and MethodsSurveillance, Epidemiology, and End Results- Medicare linked database was used to determine the relationship between type of imaging leading to thyroid cancer diagnosis and survival. Disease- specific and overall survival were evaluated in 11,945 patients aged - ¥66- years with differentiated thyroid cancer diagnosed between January 1, 2001, and September 30, 2015, who prior to their cancer diagnosis initially underwent thyroid ultrasound versus other imaging capturing the neck. Analyses were performed using the Kaplan- Meier method and Cox proportional hazards model with propensity score.ResultsPatients who underwent thyroid ultrasound as compared with other imaging had improved disease- specific and overall survival (p < .001, p < .001). However, those who underwent thyroid ultrasound were less likely to have comorbidities (p < .001) and more likely to be younger (p < .001), be female (p < .001), have localized cancer (p < .001), and have tumor size - ¤1 cm (p < .001). After using propensity score analysis and adjusting for tumor characteristics, type of initial imaging still correlated with better overall survival but no longer correlated with better disease- specific survival.ConclusionThere is improved disease- specific survival in patients diagnosed with thyroid cancer after thyroid ultrasound as compared with after other imaging. However, better disease- specific survival is related to these patients being younger and healthier and having lower- risk cancer, suggesting that thyroid ultrasound screening contributes to cancer overdiagnosis.Implications for PracticeThe findings from this study have implications for patients, physicians, and policy makers. Patients who have thyroid ultrasound as their initial imaging are fundamentally different from those who are diagnosed after other imaging. Because patients undergoing ultrasound are younger and healthier and are diagnosed with lower- risk thyroid cancer, they are less likely to die of their thyroid cancer. However, being diagnosed with thyroid cancer can lead to cancer- related worry and create risks for harm from treatments. Thus, efforts are needed to reduce inappropriate use of ultrasound, abide by the U.S. Preventive Services Task Force recommendations, and apply nodule risk stratification tools when appropriate.Because cancer overdiagnosis can be associated with both earlier detection and the detection of slower- growing tumors, overdiagnosis can lead to perceived improvement in survival. This article reports on the relationship between type of imaging and survival, using SEER- Medicare data to assess the initial imaging associated with cancer detection and disease- specific and overall survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162764/2/onco13329_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162764/1/onco13329.pd

Comparison of Patient Outcomes Before and After Switching From Warfarin to a Direct Oral Anticoagulant Based on Time in Therapeutic Range Guideline Recommendations

This cohort study evaluates stroke and major bleeding rates before and after switching from warfarin to a direct oral anticoagulant (DOAC) in patients grouped by pre-switch time-in-therapeutic range guideline thresholds