Decision Regret Following the Choice of Surgery or Active Surveillance for Small, Low-Risk Papillary Thyroid Cancer: A Prospective Cohort Study.

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3-18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery.

Gender Differences in Fears Related to Low-Risk Papillary Thyroid Cancer and Its Treatment.

Importance: Fear is commonly experienced by individuals newly diagnosed with papillary thyroid cancer (PTC). Objective: To explore the association between gender and fears of low-risk PTC disease progression, as well as its potential surgical treatment. Design, Setting, and Participants: This single-center prospective cohort study was conducted at a tertiary care referral hospital in Toronto, Canada, and enrolled patients with untreated small low risk PTC (<2 cm in maximal diameter) that was confined to the thyroid. All patients had a surgical consultation. Study participants were enrolled between May 2016 and February 2021. Data analysis was performed from December 16, 2022, to May 8, 2023. Exposures: Gender was self-reported by patients with low-risk PTC who were offered the choice of thyroidectomy or active surveillance. Baseline data were collected prior to the patient deciding on disease management. Main Outcomes and Measures: Baseline patient questionnaires included the Fear of Progression-Short Form and Surgical Fear (referring to thyroidectomy) questionnaires. The fears of women and men were compared after adjustment for age. Decision-related variables, including Decision Self-Efficacy, and the ultimate treatment decisions were also compared between genders. Results: The study included 153 women (mean [SD] age, 50.7 [15.0] years) and 47 men (mean [SD] age, 56.3 [13.8] years). There were no significant differences in primary tumor size, marital status, education, parental status, or employment status between the women and men. After adjustment for age, there was no significant difference observed in the level of fear of disease progression between men and women. However, women reported greater surgical fear compared with men. There was no meaningful difference observed between women and men with respect to decision self-efficacy or the ultimate treatment choice. Conclusions and Relevance: In this cohort study of patients with low-risk PTC, women reported a higher level of surgical fear but not fear of the disease compared with men (after adjustment for age). Women and men were similarly confident and satisfied with their disease management choice. Furthermore, the decisions of women and men were generally not significantly different. The context of gender may contribute to the emotional experience of being diagnosed with thyroid cancer and its treatment perception.

Outcomes of Early Transition of Low-Risk Thyroid Cancer Patients from Specialist to Primary Care.

BACKGROUND: Recently published clinical pathways for management of thyroid cancer outlined the criteria for transitioning low-risk patients to primary care within one to five years from diagnosis. However, discharge patterns among endocrinologists remain heterogeneous as there lacks a consensus regarding post-treatment care for thyroid cancer patients. OBJECTIVE: This study described general characteristics and outcomes of thyroid cancer patients who were discharged from specialist care and transitioned to a primary care-based follow-up clinic. METHODS: Thyroid cancer patients seen in the After Cancer Treatment Transition (ACTT) clinic at Women's College Hospital (Toronto, Canada) were included in the study. Electronic medical records were reviewed between May and October 2021 to collect patient characteristics and outcomes. Descriptive statistics were calculated. RESULTS: The study cohort included 148 thyroid cancer patients and 76% were female. All cases were papillary thyroid cancer and most diagnoses were classified as T2 (42%), N0 (55%), M0 (91%), and stage 1 (83%). Nearly all patients (n = 147) had complete thyroidectomy. Levels of thyroglobulin and thyroglobulin antibodies (TgAb) were low overall, with only 5% of the study cohort deemed TgAb positive. Mean levels of thyroid stimulating hormone (TSH) measured at 2 time points (1.37 mIU/L, 1.42 mIU/L) were within normal range. About 91% of the study cohort had normal TSH levels and 82% met target TSH levels. There were 2 cases of recurrence; however, investigation determined that they were not initially appropriate candidates for transition to primary care. Nearly 99% (n = 146) of patients had excellent response to therapy, showed no evidence of disease recurrence, and have not required re-referral to specialist care. CONCLUSIONS: These findings may reassure specialists that low-risk, stable thyroid cancer patients can be safely transitioned to primary care for post-treatment follow-up.

Genetic susceptibility to hereditary non-medullary thyroid cancer.

Non-medullary thyroid cancer (NMTC) is the most common type of thyroid cancer. With the increasing incidence of NMTC in recent years, the familial form of the disease has also become more common than previously reported, accounting for 5-15% of NMTC cases. Familial NMTC is further classified as non-syndromic and the less common syndromic FNMTC. Although syndromic NMTC has well-known genetic risk factors, the gene(s) responsible for the vast majority of non-syndromic FNMTC cases are yet to be identified. To date, several candidate genes have been identified as susceptibility genes in hereditary NMTC. This review summarizes genetic predisposition to non-medullary thyroid cancer and expands on the role of genetic variants in thyroid cancer tumorigenesis and the level of penetrance of NMTC-susceptibility genes.

A Quantitative Analysis Examining Patients' Choice of Active Surveillance or Surgery for Managing Low-Risk Papillary Thyroid Cancer.

Background: It is important to understand patient preferences on managing low-risk papillary thyroid cancer (PTC). Methods: We prospectively followed patients with low-risk PTC <2 cm in maximal diameter, who were offered the choice of thyroidectomy or active surveillance (AS) at the University Health Network (UHN), in Toronto, Canada. The primary outcome was the frequency of AS choice (percentage with confidence interval [CI]). Univariate and multivariable analyses were performed to identify predictors of the choice of AS. Results: We enrolled 200 patients of median age 51 years (interquartile range 42-62). The primary tumor measured >1 cm in 55.5% (111/200) of participants. The AS was chosen by 77.5% [71.2-82.7%, 155/200] of participants. In a backwards conditional regression model, the clinical and demographic factors independently associated with choosing AS included: older age (compared with referent group <40 years)-age 40-64 years-odds ratio (OR) 2.78 [CI, 1.23-6.30, p = 0.014], age ≥65 years-OR 8.43 [2.13-33.37, p = 0.002], and education level of high school or lower-OR 4.41 [1.25-15.53, p = 0.021]; AS was inversely associated with the patient's surgeon of record being affiliated with the study hospital-OR 0.29 [0.11-0.76, p = 0.012]. In a separate backwards conditional logistic regression model examining associations with psychological characteristics, AS choice was independently associated with a fear of needing to take thyroid hormones after thyroidectomy-OR 1.24 [1.11-1.39, p < 0.001], but inversely associated with fear of PTC progression-OR 0.94 [0.90-0.98, p = 0.006] and an active coping mechanism ("doing something")-OR 0.43 [0.28-0.66, p < 0.001]. Conclusions: Approximately three-quarters of our participants chose AS over surgery. The factors associated with choosing AS included older age, lower education level, and having a surgeon outside the study institution. Patients' fears about either their PTC progressing or taking thyroid hormone replacement as well as the level of active coping style were associated with the decision. Our results inform the understanding of patients' decisions on managing low-risk PTC. Registration: Clinicaltrials.gov NCT03271892.

Weight-based thyroid dosing vs fixed dosing during pregnancy for subclinical hypothyroidism: A retrospective cohort study.

OBJECTIVE: Thyroid hormones play a crucial role in foetal growth and neurocognitive development. Our aim was to compare a weight-based dosing method of starting thyroxine to a fixed-dose method in newly diagnosed women with subclinical hypothyroidism during pregnancy. DESIGN: We performed a retrospective cohort study of consecutive women with newly diagnosed subclinical hypothyroidism during pregnancy seen at Mount Sinai Hospital and Women's College Hospital, Toronto, Canada 2015-2018. PATIENTS: We identified women that were treated based on pre-pregnancy weight and those that were given a fixed dose of 50 mcg/day. MEASUREMENTS: The percent of women who reached the target TSH of <2.5 mIU/L within 4-8 weeks was compared using a chi-squared test and a logistic regression model, adjusting for age, initial TSH and gestational age treatment was started. RESULTS: 393 women were included: 252 treated using a fixed-dose approach; 141 treated based on pre-pregnancy weight. In the unadjusted analysis, there was no difference between the groups in the percentage of women in the target range within 4-8 weeks (89.6% in the fixed-dose group vs 88.8% in the weight-based group (p = .954)). However, after adjustment for between-group differences in age, initial TSH and gestational age treatment was started, there was a significantly greater odds of achieving the target range using the weight-based dosing (OR 4.26 (1.60-11.7), p = .004). CONCLUSIONS: Treating women with newly diagnosed subclinical hypothyroidism during pregnancy with a weight-based strategy increased the odds of reaching the target TSH range within 4-8 weeks. Clinicians caring for these women should consider this approach when starting treatment during pregnancy.

Potential diabetes overtreatment and risk of adverse events among older adults in Ontario: a population-based study.

AIMS/HYPOTHESIS: More than 25% of older adults (age ≥75 years) have diabetes and may be at risk of adverse events related to treatment. The aim of this study was to assess the prevalence of intensive glycaemic control in this group, potential overtreatment among older adults and the impact of overtreatment on the risk of serious events. METHODS: We conducted a retrospective, population-based cohort study of community-dwelling older adults in Ontario using administrative data. Participants were ≥75 years of age with diagnosed diabetes treated with at least one anti-hyperglycaemic agent between 2014 and 2015. Individuals were categorised as having intensive or conservative glycaemic control (HbA1c <53 mmol/mol [<7%] or 54-69 mmol/mol [7.1-8.5%], respectively), and as undergoing treatment with high-risk (i.e. insulin, sulfonylureas) or low-risk (other) agents. We measured the composite risk of emergency department visits, hospitalisations, or death within 30 days of reaching intensive glycaemic control with high-risk agents. RESULTS: Among 108,620 older adults with diagnosed diabetes in Ontario, the mean (± SD) age was 80.6 (±4.5) years, 49.7% were female, and mean (± SD) diabetes duration was 13.7 (±6.3) years. Overall, 61% of individuals were treated to intensive glycaemic control and 21.6% were treated to intensive control using high-risk agents. Using inverse probability treatment weighting with propensity scores, intensive control with high-risk agents was associated with nearly 50% increased risk of the composite outcome compared with conservative glycaemic control with low-risk agents (RR 1.49, 95% CI 1.08, 2.05). CONCLUSIONS/INTERPRETATION: Our findings underscore the need to re-evaluate glycaemic targets in older adults and to reconsider the use of anti-hyperglycaemic medications that may lead to hypoglycaemia, especially in setting of intensive glycaemic control.

Endocrinologist-Perceived Factors Affecting the Transition of Thyroid Cancer Patients from Specialist to Primary Care Postcancer Treatment in Ontario, Canada.

Background: Thyroid cancer patient discharge patterns from specialists are heterogeneous, with some specialists following patients for a longer period of time than others. With no well-established transitional plan, such as in breast and colorectal cancer, primary care physicians play a variable role in long-term thyroid cancer care. The objective of this study was to examine endocrinologist-perceived factors affecting the transition of care for thyroid cancer patients through a qualitative and quantitative survey of practicing endocrinologists in Ontario, Canada. Methods: All eligible practicing endocrinologists in Ontario were invited to participate in the study, via an email with an embedded survey link. Consent was assumed if the physician completed the survey. The survey collected physician demographics and asked a series of Likert-scale and open-ended questions on their views regarding transitioning care of their thyroid cancer patients. Quantitative analysis was based on mode and variability. Qualitative analysis was completed using inductive thematic analysis. Results: Seventy physicians completed the survey, with a response rate of 35.5%. Based on the responses to the Likert-scale questions, there was a lack of consensus in terms of discharging criteria for patients who had low-risk papillary thyroid cancer, stable thyrotropin levels, multiple nonthyroid-related comorbidities, and hemithyroidectomy with no disease recurrence. The majority of endocrinologists responded that the main factors affecting discharge included whether the primary care physician was able to follow their recommendations, whether the primary care physician could appropriately adjust levothyroxine doses, and whether the patient was confident that their primary care physician could manage their thyroid cancer follow-up. Themes extracted from the open-ended question also indicated that the main factors affecting the transition of care were related to the primary care physician, the patient, the imaging interpretation, and the discharge guidelines. Conclusion: The lack of consensus among endocrinologists affects the transition of patient care, and there is a need to provide clear and accurate information to primary care physicians and thyroid cancer patients on postcancer treatment care. Efforts should be sought to standardize discharge and long-term care.

Type 2 Diabetes in Older Adults in Long-Term Care Homes: An Educational Intervention to Improve Diabetes Care.

OBJECTIVES: Over 25% of nursing home residents have diabetes. Nurses (registered nurses and registered practical nurses), registered dietitians and personal support workers (PSWs) provide the bulk of diabetes care in long-term care (LTC) homes, but their self-rated diabetes knowledge is poor. In this study, we evaluated the impact of an educational intervention on comfort with, and knowledge of, diabetes management among frontline LTC staff. METHODS: We implemented an educational intervention in 2 LTC homes in Ontario that targeted nurses and dietitians, PSWs and physicians. A self-assessment questionnaire and a knowledge test were administered to nurses and dietitians and PSWs before and after the intervention. We also measured pre- and postintervention glycated hemoglobin levels, use of sliding scale insulin and type and dose of diabetes medications prescribed. RESULTS: After the intervention, both the nurses and dietitians and PSWs groups demonstrated increased comfort with diabetes management and improved self-appraised knowledge. Among PSWs, knowledge of foot care improved the most, and the nurses and dietitians group had the greatest improvement in knowledge of blood glucose monitoring. In addition, there was reduced use of sliding scale insulin, and in the number of residents requiring renal-based dose reductions of glucose-lowering medications. This intervention was innovative as it targeted different LTC health-care providers; it demonstrated the potential to increase LTC health-care providers' confidence in diabetes management. Future studies could assess the clinical benefits of an educational intervention on rates of hypoglycemia and improving A1C targets. CONCLUSIONS: An educational intervention can improve knowledge and comfort of diabetes management of frontline LTC staff.

A Prospective Mixed-Methods Study of Decision-Making on Surgery or Active Surveillance for Low-Risk Papillary Thyroid Cancer.

Background: Active surveillance (AS) of small, low-risk papillary thyroid cancers (PTCs) is increasingly being considered. There is limited understanding of why individuals with low-risk PTC may choose AS over traditional surgical management. Methods: We present a mixed-methods analysis of a prospective observational real-life decision-making study regarding the choice of thyroidectomy or AS for management of localized, low-risk PTCs <2 cm in maximum diameter (NCT03271892). Patients were provided standardized medical information and were interviewed after making their decision (which dictated disease management). We evaluated patients' levels of decision-self efficacy (confidence in medical decision-making ability) at the time information was presented and their level of decision satisfaction after finalizing their decision (using standardized questionnaires). We asked patients to explain the reason for their choice and qualitatively analyzed the results. Results: We enrolled 74 women and 26 men of mean age 52.4 years, with a mean PTC size of 11.0 mm (interquartile range 9.0, 14.0 mm). Seventy-one patients (71.0% [95% confidence interval 60.9-79.4%]) chose AS over surgery. Ninety-four percent (94/100) of participants independently made their own disease management choice; the rest shared the decision with their physician. Participants had a high baseline level of decision self-efficacy (mean 94.3, standard deviation 9.6 on a 100-point scale). Almost all (98%, 98/100) participants reported high decision satisfaction. Factors reported by patients as influencing their decision included the following: perceived risk of thyroidectomy or the cancer, family considerations, treatment timing in the context of life circumstances, and trust in health care providers. Conclusions: In this Canadian study, ∼7 out of 10 patients with small, low-risk PTC, who were offered the choice of AS or surgery, chose AS. Personal perceptions about cancer or thyroidectomy, contextual factors, family considerations, and trust in health care providers strongly influenced patients' disease management choices.

Risk for Thyroid Cancer Recurrence Is Higher in Men Than in Women Independent of Disease Stage at Presentation.

Background: Well-differentiated thyroid cancer (DTC) presents at a more advanced stage in men than in women, and the mortality in men is higher than that in women. However, it is not clear whether DTC recurrence is affected by sex independent of stage at presentation. The objective of the present study was to assess if male sex is an independent risk factor for recurrence of DTC. Methods: The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe patterns of care for thyroid cancer. We included patients from the CANNECT registry with DTC diagnosed at age 18 or older between 2000 and 2010. We compared men and women with respect to presentation, management, and recurrence risk, stratified for American Joint Committee on Cancer (AJCC) stage. Results: We included 2595 patients, 2067 (79.7%) women and 528 (20.3%) men. Men presented with more advanced AJCC stage (p < 0.001), T stage (p < 0.001), N stage (p < 0.001), and M stage (p = 0.002) There was no difference in follow-up duration between women (7.7 ± 4.0 [mean ± standard deviation] years) and men (7.7 ± 4.0 years, p = 0.985). Overall recurrence was 2.2% (n = 46) for women and 8.5% (n = 45) for men (p < 0.001). In multivariate analysis adjusted for AJCC stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.72 [95% confidence interval [CI] 1.78-4.20]; p < 0.001). In multivariate analysis adjusted for tumor-node-metastasis (TNM) stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.31 [CI 1.48-3.60]; p < 0.001). Conclusions: Our study confirms that the risk for recurrence of DTC is higher in men than in women. Although men tend to present with more advanced-stage disease, the difference in recurrence risk persists when adjusted for stage of presentation. It needs to be determined whether sex should influence follow-up intensity and/or duration.

A systematic review of randomized controlled trials for management of persistent post-treatment fatigue in thyroid cancer survivors.

BACKGROUND: Fatigue that persists post-treatment is commonly reported by thyroid cancer (TC) survivors. METHODS: A systematic review of published English language randomized controlled trials (RCTs) on interventions for management of persistent post-treatment fatigue in TC was conducted. This review excluded studies on short-term interventions used in preparation for radioactive iodine diagnostic scans or treatment. An electronic search was executed in six databases and supplemented by a hand search. Two reviewers independently reviewed all citations from the electronic search and relevant full-text studies. Two abstractors independently critically appraised included studies and abstracted the data. The data were qualitatively summarized. RESULTS: A total of 1086 unique citations and 25 full-text studies were reviewed. Four studies summarizing the results of three RCTs were included. The interventions included: combination triiodothyronine with levothyroxine (L-T4) therapy compared to L-T4 alone (one RCT), reduction in degree of thyrotropin (TSH) suppression using L-T4 compared to maintenance of TSH suppression (one RCT), and supervised exercise compared to inactivity (two RCTs examining different fatigue outcomes in same population). Trial duration ranged from 10 weeks to six months. All trials had limitations, and the number of TC survivors included in respective RCTs ranged from 15 to 36. Hormonal treatment RCTs had mixed fatigue outcome results within respective trials. However, multiple measures suggesting improvement in fatigue were reported following the exercise intervention. CONCLUSIONS: There is paucity of RCTs to guide evidence-based management of persistent post-treatment fatigue in TC survivors. RCTs of interventions for prevention or treatment of fatigue in TC survivors are needed.

Persistent posttreatment fatigue in thyroid cancer survivors: a scoping review.

The relevance of persistent posttreatment fatigue (PPF) to thyroid cancer (TC) survivor populations is not known. This article presents a scoping review, which is an overview of published research activity. Uncontrolled data suggest that PPF is one of the most common complaints in TC survivors. Furthermore, statistically significantly worse levels of fatigue were reported in TC survivors, compared with the general population or healthy controls. There was some inconsistency among PPF risk factors. More research is needed on PPF in TC survivors, including long-term prospective cohort studies, research on fatigue severity prevalence, and randomized controlled trials of treatment strategies.

Randomized controlled trial of a computerized decision aid on adjuvant radioactive iodine treatment for patients with early-stage papillary thyroid cancer.

PURPOSE: Decision-making on adjuvant radioactive iodine (RAI) treatment for early-stage papillary thyroid cancer (PTC) is complex because of uncertainties in medical evidence. Using a parallel, two-arm, randomized, controlled trial design, we examined the impact of a patient-directed computerized decision aid (DA) on the medical knowledge and decisional conflict in patients with early-stage PTC considering the choice of being treated with adjuvant RAI or not. The DA describes the rationale, possible risks and benefits, and the medical evidence uncertainty relating to the choice. PATIENTS AND METHODS: We recruited 74 patients with early-stage PTC after thyroidectomy. Participants were assigned by using 1:1 central computerized randomization to either the DA group with usual care (intervention) or usual care alone (control). Medical knowledge about PTC and RAI treatment (the primary outcome), as well as decisional conflict (a secondary outcome), were measured by using validated questionnaires, and the respective scores were compared between groups. RESULTS: Consistent with PTC epidemiology, 83.8% (62 of 74) of the participants were women, and the mean age was 45.8 years (range, 19 to 79 years). Medical knowledge about PTC and RAI treatment was significantly greater and decisional conflict was significantly reduced in the DA group compared with the control group (respective P values < .001). The use of adjuvant RAI treatment was not significantly different between groups (DA group, 11 of 37 [29.7%]; controls, seven of 37 [18.9%]; P = .278). CONCLUSION: A computerized DA improves informed decision making in patients with early-stage PTC who are considering adjuvant RAI treatment. DAs are useful for patients facing decisions subject to medical evidence uncertainty.