Search

Introduction: Multikinase inhibitors have clinical activity in radioactive iodine refractory (RAIR) differentiated thyroid cancers (DTCs) but are not curative; optimal management and salvage therapies remain unclear. This study assessed clinical effects of pazopanib therapy in RAIR-DTC patients with progressive disease, examining in parallel biomarker that might forecast/precede therapeutic response. Methods: Assessment of responses and toxicities and of any association between thyroglobulin (Tg) changes cycle 1 and RECIST (response evaluation criteria in solid tumors) response to pazopanib therapy were prospectively undertaken in Tg antibody negative RAIR-DTC patients. RECIST progressive metastatic disease <6 months preceding enrollment was required. With a sample size of 68 (assuming 23 attaining partial response [PR]), there would be 90% chance of detecting a difference of >30% when the proportion of patients attaining PR whose Tg values decrease by >50% is >50% cycle 1 (one-sided α  = 0.10, two sample test of proportions). Mean corpuscular volume (MCV) change or mutational status or pretreatment were also explored as early correlates of eventual RECIST response. Results: From 2009 to 2011, 60 individuals were treated and evaluated; (one additional patient withdrew; another was found ineligible before therapy initiation); 91.7% had previous systemic therapy beyond RAI. Adverse events included one death (thromboembolic) deemed possibly pazopanib associated. Twenty-two confirmed RECIST PRs resulted (36.7%, confidence interval; CI [24.6-50.1]); mean administered 4-week cycles was 10. Among 44 fully accessible patients, the Tg nadir was greater among the 20 attaining PR (median: -86.8%; interquartile range [IQR]: -90.7% to -70.9%) compared with the 28 who did not (median: -69.0%; IQR: -78.1% to -27.7%, Wilcoxon rank-sum test: p  = 0.002). However, the difference in the proportion of PRs among those whose Tg fell ≥50% after cycle 1 versus those that did not were not significantly correlated (-23.5% [CI: -55.3 to 8.3]; Fisher's exact test p -value = 0.27). RECIST response was also not correlated with/predicted by early MCV change, receipt of prior therapy, or tumor mutational status. Conclusions: This trial prospectively confirmed pazopanib to have clinical activity and manageable toxicities in patients with progressive RAIR-DTC. Response to pazopanib, however, was not robustly forecast by early associated changes in Tg or MCV, by prior therapy, or by tumor mutational status. ClinicalTrials.gov NCT00625846.

Background: Management of patients with thyroglobulin (Tg)-positive/scan-negative thyroid cancer remains challenging. American Thyroid Association (ATA) guidelines recommend potential use of empiric (131)I therapy and various scanning modalities, but no standard for managing such cases exists., Methods: We surveyed ATA members to assess current practice in management of patients with Tg-positive/scan-negative disease. Members participated in a web-based survey of six case scenarios of Tg elevations but iodine scan negativity., Results: A total of 288 ATA members (80% male) participated. Patient age, sex, and basal and stimulated Tg varied between the cases. Respondents were asked their opinion regarding empiric (131)I therapy use, including (131)I dose, use and duration of low-iodine diet, thyroxine withdrawal or recombinant human thyrotropin (rhTSH), and utilization of additional imaging (neck ultrasound (US) or positron emission tomography/computed tomography (PET/CT)) and reconsideration of (131)I therapy. Between 16% and 51% recommended initial use of empiric (131)I for the various scenarios. The majority chose a (131)I dose between 75 and 150 mCi, and 73% employed a low-iodine diet for two or more weeks. Preference between thyroxine withdrawal versus rhTSH was evenly split. More than 98% obtained a neck US if empiric (131)I was not given; 52-89% would proceed to PET/CT if US was negative. Only 44% used rhTSH stimulation in PET scan preparation. (131)I use was more common with stimulated Tg significantly >10 ng/mL. (131)I therapy was slightly more likely with PET-positive (56%) than PET-negative status (45%). Respondents were split regarding empiric (131)I if basal and stimulated Tg increased ≥150% over two years. Providers in North America less commonly utilized (131)I treatment than those from other areas. In the face of possible heterophilic antibody interference in the Tg assay, the majority did not recommend (131)I therapy., Conclusions: Empiric (131)I therapy is still utilized for patients with Tg-positive/scan-negative disease. Neck US is frequently used to further evaluate such cases as (18)FDG-PET/CT, albeit the latter is used somewhat less often. Use of (131)I therapy correlated with the degree of Tg elevation or development of Tg antibodies, and was recommended more commonly with PET-positive than PET-negative status in patients with lower Tg levels. (131)I was less commonly used by providers within North America.

Context: Most thyroglobulin (Tg) assays have a sensitivity of 0.5-1 ng/ml. A minority of patients with undetectable T4-suppressed Tg levels have a recombinant human TSH (rhTSH)-stimulated Tg above 2 ng/ml and identifiable residual disease., Objective: The objective was to determine whether a Tg assay with improved sensitivity could eliminate the need for rhTSH stimulation when baseline Tg is below 0.1 ng/ml., Design: A retrospective study of two academic endocrine practices was conducted., Population: A total of 194 patients undergoing rhTSH stimulation participated in the study., Results: Of the 80 patients with Tg below 0.1 ng/ml, two (2.5%) had rhTSH-stimulated Tg above 2 ng/ml. One other patient with stimulation to 0.3 ng/ml and negative 123I scan had an ultrasound-detected malignant lymph node resected. None had 131I/123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. If T4-suppressed Tg was 0.1-0.5 or 0.6-2.0 ng/ml, rhTSH Tg was above 2 ng/ml in 24.2 and 82.4%, respectively., Conclusions: Patients with differentiated thyroid carcinoma and a T4-suppressed serum Tg below 0.1 ng/ml rarely have a rhTSH-stimulated Tg above 2 ng/ml, and none of these patients had 131I or 123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. We recommend monitoring such patients with a T4-suppressed Tg level and periodic neck ultrasonography. An increase in T4-suppressed serum Tg to a detectable level or the appearance of abnormal lymph nodes by physical or ultrasound exam should prompt further investigation.