ResearchPad - thyroid-autoimmunity-and-benign-thyroid-disease Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[OR18-06 Thyroid Function Test Abnormalities Secondary to Immune-Checkpoint Inhibitors: A Marker of Survival?]]> Immune-checkpoint inhibitors (ICI) are monoclonal antibodies which target molecules to enhance antitumor response. Several adverse events have been described and the major ICI-related endocrinopathies are thyroid dysfunction and hypophysitis. Its occurrence has been associated with increased survival.

A retrospective study of adult patients treated with ICI between March 2014 and September 2019 at an oncologic centre was performed to evaluate the impact of thyroid function test abnormalities (TFTA) in their prognosis. We excluded patients without regular monitoring of thyroid function, with previous thyroid or pituitary disease (including medical and surgical treatments), previous head/neck radiotherapy and who performed only one ICI cycle. Clinical data of all patients were examined independently by two Endocrinologists. Survival analysis was performed using the Kaplan-Meier method. Cox regression was used to evaluate associations between the occurrence of TFTA and the outcome of overall survival (OS). It was adjusted for sex, age, primary neoplasm, tumor staging and ICI. All analyses were performed using IBM-SPSS v.25 and a level of significance α=0.05 was noted.

We included 161 of 205 patients, with a median age of 65 years [Interquartile range (IQR) 15] and 67% male. Most patients had melanoma (52%) and lung cancer (43%). Globally, 86, 59 and 25 patients were under pembrolizumab, nivolumab and ipilimumab, respectively. Median duration of ICI treatment was 4.4 months (IQR 7.7) and median total follow‐up was 11.4 months (IQR 11.2). New onset TFTA was diagnosed in 18% of patients, at median age of 65 years (IQR 20) and 55% male. Almost half (45%) had primary hypothyroidism, 28% had central hypothyroidism and 13.8% had biphasic thyroiditis and thyrotoxicosis, each. Most TFTA (79%) occurred under pembrolizumab and nivolumab. Grade 2 CTCAE was the most frequently reported. None of the events led to ICI suspension.

Patients with TFTA underwent a significant higher number of ICI cycles than control group [median 11 cycles (IQR 20) vs 7 (IQR 11), p=0.017] and had a higher period under ICI (median of 7.6 months (IQR 13.8) vs 4.2 (IQR 7.7), p=0.026). Comparison between TFTA patients and control group did not reveal statistical differences in patients’ age and sex, primary neoplasm, tumor staging and ICI.

Overall survival was significantly higher in patients that developed TFTA during treatment with ICI, comparing to the control group (mean OS 3.62 years vs 1.92 years, p=0.033). The risk of mortality was higher for the control group, approximately 3 times, considering the adjustment for the covariates (HR 2.94, 95%CI=1.18 to 7.34, p=0.021). Overall survival was not affected by the covariates.

Our study shows that patients under ICI that develop primary or central thyroid dysfunction had an improved survival. In these patients, the occurrence of TFTA could be a marker of a better response to ICI.

<![CDATA[OR18-07 Laser Ablation Versus Radiofrequency Ablation for Benign Non-Functioning Thyroid Nodules: Six-Month Results of a Randomised, Parallel, Open-Label, Trial (Lara Trial)]]> ABSTRACT

Background: Up to now, there are no direct prospective studies comparing Laser (LA) and radiofrequency ablation (RFA). We aimed to compare, in a head- to-head clinical trial, the efficacy and safety of both techniques in a population affected by solid or predominantly solid benign non-functioning thyroid nodules (BNTN).

Methods. LARA is a six-month, single-use, randomized, superiority, open-label, parallel trial. We enrolled subjects with a solitary BNTN or dominant nodule characterized by pressure symptoms/cosmetic problems or patients without symptoms who experienced a volume increase >20% in one year. Nodules underwent core needle biopsy (CNB) to evaluate the histological architecture. Patients were randomly assigned (1:1) to receive treatment with either LA or RFA. The primary endpoint was to evaluate the difference in nodule volume reduction between the RF and the LA group at six months. Moreover, we aimed to assess the differences between groups in the rate of nodules with greater than 50% base volume reduction (successful rate) at six months after treatment. number NCT02714946.

Findings: From January 2016 to November 2018, 60 patients were randomly assigned (30 participants per group). In the whole study population, the average volume of nodules was 25 ml. The two groups were similar in terms of basal nodule volume, thyroid function, histology, symptoms/cosmetic score and procedure time. At six months, participants in the RFA group showed a reduction volume of 64·3% (95% CI: 57·5% - 71·2%) compared to 53·2% (95% CI: 47·2% - 59·2%) in the LA group (p= 0·015) and this difference was also confirmed in a linear regression model adjusted for age, baseline volume and proportion of cellular component (Laser vs. RFA percent change Delta= -12·8, P=0·018).We have not recorded any significant difference in terms of successful rate at six months after treatment between the two groups (86·7% in the RFA vs 66·7% in the LA, p=0·127). At six months, both symptoms and cosmetic scores improved (compressive symptom score: 2·13 vs 3·9 for RFA, p < 0·001; 2·4 vs. 3·87 for LA, p < 0·001; cosmetic score: 1·65 vs 2·2 for RFA p <0·001, 1·85 vs 2·2 for LA p <0·001) without any statistically significant difference between the two groups. No statistical difference between the two groups was detected at six months as regards the TSH level. High rate of cellularity negatively affects the volume reduction in RFA group (r coefficient -0·41, p=0·034) while histological features did not affect the efficacy of the LA. The adverse event rates were 37% and 43% for RFA and LA, respectively, with no requirement for hospitalization.

Interpretation: Both techniques are very effective in reducing the volume of thyroid nodules. RFA appears to be more effective than LA, but both techniques showed no difference in terms of success rate six months after treatment. The safety of the two techniques is very satisfactory.

<![CDATA[OR18-01 Effect of Teprotumumab on Proptosis Reduction Across Various Demographic Sub-Groups]]> Introduction: Teprotumumab, an insulin-like growth factor 1 receptor inhibitory monoclonal antibody, was recently shown to significantly reduce proptosis in patients with active, moderate-to-severe thyroid eye disease (TED) in phase 2 and phase 3 clinical trials.1,2 Prior analyses have demonstrated a combined trial proptosis response (≥2 mm reduction) rate of 77.4% in the teprotumumab group and 14.9% in the placebo group after 24 weeks of therapy (p < 0.001).3 The current analysis was performed to investigate whether or not patient demographic characteristics influence the teprotumumab proptosis response.

Methods: Data from two 24-week randomized, double-masked, placebo-controlled, parallel-group, multicenter studies (Phase 2 [NCT01868997], Phase 3 [NCT03298867[) were combined. All patients had active TED associated with Graves’ disease. The study eye designated at baseline manifested more severe TED and a clinical activity score of > 4. Subjects were divided into subgroups based on gender, smoking status, and age at baseline (younger: <65, older: ≥65). The percentage of proptosis (≥2 mm) responders and proptosis change from baseline were examined in each of these subgroups. Because most of both teprotumumab (85%) and placebo (87%) subjects were white, there were insufficient numbers of subjects to examine the effect of race on the teprotumumab proptosis response. All analyses were performed on the intent-to-treat (ITT) population using data from the study eye.

Results: A total of 171 patients comprised the population from the two studies. Eighty-four and 87 patients were randomized to the teprotumumab and placebo groups, respectively, and the treatment groups had balanced baseline characteristics. At week 24, significantly more teprotumumab than placebo patients were proptosis responders in all examined subgroups (male: 73.1% vs. 5.0%, female: 79.3% vs. 17.9%, smokers: 70.0% vs. 23.1%, non-smokers 79.7% vs. 11.5%, younger: 76.1% vs. 16.2%, older: 84.6% vs. 7.7%; all p < 0.001). In continuous variable analyses, the mean proptosis reduction from baseline was also significantly greater at week 24 in teprotumumab-treated patients than placebo patients (male: -3.34 vs. -0.07 mm, female: -3.10 vs. -0.42 mm, smokers: -2.99 vs. -0.72 mm, non-smokers: -3.20 vs. -0.31 mm, younger: -3.10 vs. -0.39 mm, older: -3.55 vs. -0.22 mm; all p < 0.001).

Conclusion: Teprotumumab was effective across subgroups of age, gender, and smoking status in the pooled 24-week clinical trials.

Reference: (1) Smith TJ, et al. N Engl J Med 2017;376:1748-1761. (2) Douglas RS, et al. AACE 2019 late-breaking abstract. (3) Kahaly GJ, et al. Thyroid 2019;29(Suppl1):A-1 [abstract].

<![CDATA[OR18-03 Functional TSH Receptor Antibodies Are a Biomarker for Graves’ Disease - a Prospective Trial]]> 40% inhibition).ResultsForty-four patients responded to MMI of whom 43% had Graves’ orbitopathy (GO) while 56 were non-responders (66% with GO, p<0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibiting immunoglobulins (TBII) differentiated between thyroidal GD only versus GD+GO (p<0.001). Further, at baseline responders demonstrated marked differences in diluted TSAb titers compared with non-responders (p<0.001). All patients with a TSAb dilution titer above three did not respond to MMI treatment. In contrast, TBII dilution titers did not differentiate between responders and non-responders to MMI and serum samples became TBII negative already at low dilutions. During treatment, serum TSAb levels decreased markedly in responders (p<0.001) but increased in non-responders (p<0.01). In contrast, TBII strongly decreased in non-responders (p=0.002). All non-responders at week 24 and/or those who relapsed during the 72-week follow-up were TSAb positive at week 24. A shift from TSAb to TBAb was noted in eight patients during treatment and/or follow-up and led to remission.ConclusionsSerum TSAb levels are a biomarker for and mirror severity of GD. Their increase during MMI treatment is a marker for on-going disease activity. TSAb dilution analysis had additional predictive value. ]]> <![CDATA[OR18-05 Thyroid Hormone Use and Survival among Older Adults - Longitudinal Analysis of the Baltimore Longitudinal Study of Aging (BLSA)]]>