(searched for: doi:10.1001/jamaoto.2013.760)
European Journal of Cancer, Volume 157, pp 153-164; https://doi.org/10.1016/j.ejca.2021.07.029
Introduction Multikinase inhibitor (MKI) treatments have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC), but most patients experienced substantial adverse effects. This randomised multicentric study investigated intermittent versus continuous pazopanib administration. Patients and methods The PAZOTHYR study included RAIR-TC patients with progressive disease in the last 12 months, who may have received one prior MKI. RAIR-TC patients received pazopanib for 6 months, and patients with stable disease or tumour response were randomly assigned (1:1) to receive continuous (CP) or intermittent (IP) pazopanib until progression. The primary end-point was time to treatment failure (TTF) defined as the time from randomisation to permanent discontinuation of pazopanib, due to any cause. One hundred randomised patients were needed to demonstrate an increase from 50% (CP) to 70% (IP) (hazard ratio (HR) 0.515, 80% power) in the rate of patients still under treatment 6 months (6m-SuT) post-randomisation. Secondary end-points included the overall response rate (ORR), progression-free survival (PFS) under pazopanib and safety. Results RAIR-TC patients (168) enrolled from June 18, 2013 to January 16, 2018, received 6-month pazopanib treatment and showed 35.6% (95% CI 28.2–43.6) best response rate and 89.4% (83.5–93.7) disease control rate. One hundred patients were randomised (IP:50; CP:50). With a median follow-up of 31.3 months, median TTF was not statistically different between arms (IP:14.7, 95% confidence interval (CI) 9.3–17.4; CP:11.9, 95% CI 7.5–15.6) months (HR 0.79, 0.49–1.27). 6m-SuT rates were similar (IP:80% 66.0–88.7%; CP:78% 63.8–87.2%). Median PFS under pazopanib were not statistically different (IP:5.7 4.8–7.8; CP: 9.2 7.3–11.1) months (HR 1.36, 0.88–2.12). Pazopanib-related adverse events grade 3–4 occurred in 36 (IP: 19, 38%; CP: 17, 34%) randomised patients. Seven pazopanib-related deaths occurred. Conclusions Intermittent administration of pazopanib did not demonstrate significant superiority in efficacy or tolerance compared with continuous treatment. An intermittent administration scheme cannot be recommended outside clinical trials. This study was registered with ClinicalTrial.gov, number NCT01813136.
Mayo Clinic Proceedings, Volume 96, pp 1727-1745; https://doi.org/10.1016/j.mayocp.2021.02.009
Objective To determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence (TR) rate after bilateral lobar resection (BLR). Patients and Methods There were 2952 low-risk adult papillary thyroid cancer (LRAPTC) patients (with MACIS scores <6) who underwent potentially curative BLR during 1955-2014. During 1955-1974, 1975-1994, and 1995-2014, RRA was administered in 3%, 49%, and 28%. Statistical analyses were performed using SAS software. Results During 1955-1974, the 20-year CSM and TR rates after BLR alone were 1.0% and 6.8%; rates after BLR+RRA were 0% (P=.63) and 5.9% (P=.82). During 1975-1994, post-BLR 20-year rates for CSM and TR were 0.3% and 7.5%; after BLR+RRA, rates were higher at 0.9% (P=.31) and 12.8% (P=.01). When TR rates were examined separately for 448 node-negative and 317 node-positive patients, differences were nonsignificant. In 1995-2014, post-BLR 20-year CSM and TR rates were 0% and 9.2%; rates after BLR+RRA were higher at 1.4% (P=.19) and 21.0% (P<.001). In 890 pN0 cases, 15-year locoregional recurrence rates were 3.4% after BLR and 3.7% after BLR+RRA (P=.99). In 740 pN1 patients, 15-year locoregional recurrence rates were 10% higher after BLR+RRA compared with BLR alone (P=.01). However, this difference became nonsignificant when stratified by numbers of metastatic nodes. Conclusion RRA administered to LRAPTC patients during 1955-2014 did not reduce either the CSM or TR rate. We would therefore not recommend RRA in LRAPTC patients undergoing BLR with curative intent.
American Journal of Otolaryngology, Volume 40, pp 431-434; https://doi.org/10.1016/j.amjoto.2019.04.001
The publisher has not yet granted permission to display this abstract.
Annals of Surgical Oncology, Volume 26, pp 694-696; https://doi.org/10.1245/s10434-018-07102-z
The Lancet Diabetes & Endocrinology, Volume 7, pp 44-51; https://doi.org/10.1016/s2213-8587(18)30306-1
Summary Background Two large randomised trials of patients with well-differentiated thyroid cancer reported in 2012 (HiLo and ESTIMABL1) found similar post-ablation success rates at 6–9 months between a low administered radioactive iodine (131I) dose (1·1 GBq) and the standard high dose (3·7 GBq). However, recurrence rates following radioactive iodine ablation have previously only been reported in observational studies, and recently in ESTIMABL1. We aimed to compare recurrence rates between radioactive iodine doses in HiLo. Methods HiLo was a non-inferiority, parallel, open-label, randomised controlled factorial trial done at 29 centres in the UK. Eligible patients were aged 16–80 years with histological confirmation of differentiated thyroid cancer requiring radioactive iodine ablation (performance status 0–2, tumour stage T1–T3 with the possibility of lymph-node involvement but no distant metastasis and no microscopic residual disease, and one-stage or two-stage total thyroidectomy). Patients were randomly assigned (1:1:1:1) to 1·1 GBq or 3·7 GBq ablation, each prepared with either recombinant human thyroid-stimulating hormone (rhTSH) or thyroid hormone withdrawal. Patients were followed up at annual clinic visits. Recurrences were diagnosed at each hospital with a combination of established methods according to national standards. We used Kaplan-Meier curves and hazard ratios (HRs) for time to first recurrence, which was a pre-planned secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT00415233. Results Between Jan 16, 2007, and July 1, 2010, 438 patients were randomly assigned. At the end of the follow-up period in Dec 31, 2017, median follow-up was 6·5 years (IQR 4·5–7·6) in 434 patients (217 in the low-dose group and 217 in the high-dose group). Confirmed recurrences were seen in 21 patients: 11 who had 1·1 GBq ablation and ten who had 3·7 GBq ablation. Four of these (two in each group) were considered to be persistent disease. Cumulative recurrence rates were similar between low-dose and high-dose radioactive iodine groups (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 5·9% vs 7·3%; HR 1·10 [95% CI 0·47–2·59]; p=0·83). No material difference in risk was seen for T3 or N1 disease. Recurrence rates were also similar among patients who were prepared for ablation with rhTSH and those prepared with thyroid hormone withdrawal (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 8·3% vs 5·0%; HR 1·62 [95% CI 0·67–3·91]; p=0·28). Data on adverse events were not collected during follow-up. Interpretation The recurrence rate among patients who had 1·1 GBq radioactive iodine ablation was not higher than that for 3·7 GBq, consistent with data from large, recent observational studies. These findings provide further evidence in favour of using low-dose radioactive iodine for treatment of patients with low-risk differentiated thyroid cancer. Our data also indicate that recurrence risk was not affected by use of rhTSH. Funding Cancer Research UK.
Published: 1 April 2015
The Journal of Clinical Endocrinology & Metabolism, Volume 100, pp 1529-36; https://doi.org/10.1210/jc.2014-4332
Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The long-term prognosis is generally excellent. Due to a paucity of data, debate exists regarding the benefit of adjuvant radioactive iodine therapy (RAI) for intermediate-risk patients. The objective of the study was to examine the impact of RAI on overall survival in intermediate-risk PTC patients. Adult patients with intermediate-risk PTC who underwent total thyroidectomy with/without RAI in the National Cancer Database, 1998-2006, participated in the study. Intermediate-risk patients, as defined by American Thyroid Association risk and American Joint Commission on Cancer disease stage T3, N0, M0 or Mx, and T1-3, N1, M0, or Mx were included in the study. Patients with aggressive variants and multiple primaries were excluded. Overall survival (OS) for patients treated with and without RAI using univariate and multivariate regression analyses was measured. A total of 21 870 patients were included; 15 418 (70.5%) received RAI and 6452 (29.5%) did not. Mean follow-up was 6 years, with the longest follow-up of 14 years. In an unadjusted analysis, RAI was associated with improved OS in all patients (P < .001) as well as in a subgroup analysis among patients younger than 45 years (n = 12 612, P = .002) and 65 years old and older (median OS 140 vs 128 mo, n = 2122, P = .008). After a multivariate adjustment for demographic and clinical factors, RAI was associated with a 29% reduction in the risk of death, with a hazard risk 0.71 (95% confidence interval 0.62-0.82, P < .001). For age younger than 45 years, RAI was associated with a 36% reduction in risk of death, with a hazard risk 0.64 (95% confidence interval 0.45- 0.92, P = .016). This is the first nationally representative study of intermediate-risk PTC patients and RAI therapy demonstrating an association of RAI with improved overall survival. We recommend that this patient group should be considered for RAI therapy.
Surgical Clinics of North America, Volume 94, pp 573-586; https://doi.org/10.1016/j.suc.2014.03.004
The publisher has not yet granted permission to display this abstract.
Cancer, Volume 120, pp 1345-1352; https://doi.org/10.1002/cncr.28562
BACKGROUND Well‐differentiated thyroid cancer (WDTC) is a prevalent disease, which is increasing in incidence faster than any other cancer. Substantial direct medical care costs are related to the diagnosis and treatment of newly diagnosed patients as well as the ongoing surveillance of patients who have a long life expectancy. Prior analyses of the aggregate health care costs attributable to WDTC in the United States have not been reported. METHODS A stacked cohort cost analysis was performed on the US population from 1985 to 2013 to estimate the number of WDTC survivors in 2013. Incidence rates, and cancer‐specific and overall survival were based on Surveillance, Epidemiology, and End Results (SEER) data. Current and projected direct medical care costs attributable to the care of patients with WDTC were then estimated. Health care–related costs and event probabilities were based on Medicare reimbursement schedules and the literature. RESULTS Estimated overall societal cost of WDTC care in 2013 for all US patients diagnosed after 1985 is $1.6 billion. Diagnosis, surgery, and adjuvant therapy for newly diagnosed patients (41%) constitutes the greatest proportion of costs, followed by surveillance of survivors (37%), and nonoperative death costs attributable to thyroid cancer care (22%). Projected 2030 costs (in 2013 US dollars) based on current incidence trends exceed $3.5 billion. CONCLUSIONS Health care costs of WDTC are substantial. Unlike other cancers, the majority of the cost is incurred in the initial and continuing phases of care. With the projected increasing incidence, population, and survival trends, costs will continue to escalate. Cancer 2014;120:1345–1352. © 2014 American Cancer Society.
Published: 1 January 2014
Current Opinion in Oncology, Volume 26, pp 31-35; https://doi.org/10.1097/cco.0000000000000039
The incidence of well differentiated thyroid cancer (WDTC) is increasing in the US population and is now a major public health concern. Although surgery is the mainstay of treatment, radioactive iodine (RAI) is routinely used for adjuvant therapy, remnant ablation, and for the treatment of metastatic disease. Despite excellent prognosis and stable mortality rates, the use of RAI is increasing in many low and intermediate risk WDTC patients without clear indication that it changes the outcome. As a result, the current treatment paradigm has shifted towards a risk-stratified approach. Although there is widespread acceptance that RAI improves overall and recurrence-free survival in patients with metastatic disease, controversy remains regarding radioactive remnant ablation use in low and intermediate risk patients. Additional studies have shown that reduced doses of RAI can provide similar rates of remnant ablation and adjuvant therapy in low and intermediate risk patients without adversely affecting the recurrence rates and mortality. Recent studies suggest potential new paradigms in radioactive remnant ablation dosing and indications for use. Risk stratification is important in determining the proper use and dosing of RAI.