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BACKGROUND Immune checkpoint inhibitors (ICPi) cause various immune-related adverse events (irAE) with thyroid dysfunction as a commonly reported abnormality. There is increasing evidence showing positive association with development of irAE and survival. However, prior trials with ICPi had underrepresentation of minorities with < 5% African Americans. AIM To evaluate the association between development of irAE and survival outcomes among a racially diverse patient population. METHODS Data on patients with stage IV solid malignancies treated with programmed cell death-protein 1/programmed death ligand 1 blockers between January 2013 and December 2018 across MedStar Georgetown Cancer Institute facilities were retrospectively reviewed. Patients treated with cytotoxic T-lymphocyte-associated protein 4 inhibitors were excluded. Progression free survival (PFS) and overall survival (OS) were primary endpoints and were calculated using Kaplan-Meier methods and Wilcoxon rank sum test for comparison. RESULTS Out of 293 patients who met eligibility criteria, 91 pts (31%) had any grade irAE; most common AE were endocrine (40.7%) specifically TSH elevation, dermatological (23.1%) and rheumatologic (18.7%). Proportion of irAE was significantly higher in Caucasians vs African Americans (60.4% vs 30.8%), in patients with low programmed death ligand 1, lower LDH, older age, and those who had more treatment cycles with ICPi. Rate of progression was lower in patients with irAE (30.8% vs 46.0%, P = 0.0140). Median PFS (5.8 vs 3.0 mo, P = 0.0204) and OS (17.1 vs 7.2 mo, P < 0.0001) were higher with irAE. Statistically significant difference in OS (17.1 vs 8.6 mo, P = 0.0002) but not in PFS (5.8 vs 3.3 mo, P = 0.0545) was noted with endocrine irAE. No differences in survival were observed among other commonly reported irAE. Differences in survival among subgroups of patients with irAE are described. CONCLUSION Development of irAE positively correlated with improved PFS and OS as reported in previous studies. To our knowledge, this is the first study observing differences in OS favoring endocrine AE and Caucasian race. These factors may be potential surrogate markers of prognosis pending replication of these results in large-scale studies.

Differentiated thyroid cancer patients with significantly elevated or rapidly rising serum thyroglobulin (Tg) levels and negative diagnostic radioiodine scans (DxScan) often present a therapeutic dilemma in deciding whether or not to administer an 131I treatment. In this report, we describe a novel two-step approach of a 30 mCi 131I exploratory scan before a dosimetric 131I therapy to help “un-blind” the treating physician of the benefit/risk ratio of a further “blind”131I treatment. A 51-year-old man presented with rising Tg levels, a negative DxScan, and a history of widely metastatic follicular thyroid cancer. He had undergone total thyroidectomy, remnant ablation with 3.8 GBq (103.5 mCi) of 131I, Gammaknife®, and treatment with 12.1 GBq (326 mCi) of 131I for multiple metastases. However, at 19 months after the treatments, his Tg levels continued to rise, and scans demonstrated no evidence of radioiodine-avid metastatic disease. In anticipation of a “blind”131I treatment, the medical team and the patient opted for a 30 mCi exploratory scan. The total dosimetrically guided prescribed activity (DGPA) was decided based on the whole-body dosimetry. The patient was first given 30 mCi of 131I, and the exploratory scan was performed 22 h later, which demonstrated 131I uptake in the left lung, left humeral head, T10, and right proximal thigh muscle. Based on the positive exploratory scan, the remainder of the DGPA was administered within several hours after the scan. On the post-DGPA treatment scan performed at 5—7 days, the lesions seen on the ~ 22 h exploratory scan were confirmed, and an additional lesion was observed in the left kidney. The 30 mCi exploratory scan suggested the potential for a response in the radioiodine-avid lesions despite a negative diagnostic scan. This method allows 131I treatment to be administered to patients who may have a greater potential for a therapeutic response while avoiding unwarranted side effects in those patients with nonavid disease.

Introducao: E atraves da consulta seguida da prescricao que o portador de diabetes tem seu primeiro contato e informacoes quanto sua condicao clinica, a farmacoterapia correta proporciona o bem estar e o controle dos parâmetros glicemicos, o que e possivel quando o paciente passa a aderir o tratamento e se propoe a realiza-lo de acordo com suas necessidades. Metodologia: Este estudo tem como objetivo avaliar a compreensao e adesao da terapia medicamentosa de pacientes diabeticos assistidos no municipio de Verdejante-PE. Trata-se de um estudo descritivo transversal, com abordagem quanti-qualitativa, no municipio de Verdejante-PE, na Secretaria de Saude incluindo os diabeticos acima de 18 anos com cadastro regularizado. Resultados: Foi possivel perceber que esses pacientes possuem dificuldade em compreender nao so a prescricao medica como tambem o porque de fazer uso dos medicamentos, apesar disso a terapia medicamentosa e administrada de forma coerente, quase todos os usuarios nao praticam a automedicacao o que reduz as chances de possiveis interacoes e riscos durante o tratamento. Conclusao: A autovigilância e essencial, e com o surgimento de duvidas voltadas a esse processo os portadores buscam e tem a assistencia necessaria dos profissionais da saude, onde recebem as orientacoes e procuram segui-las.

As plantas sao usadas de forma medicinal ha muito tempo, em dias atuais, se consolidam como meio terapeutico. Tendo eficacia comprovada, sao necessarios incentivos para que as plantas se instalem bem em areas rurais, justamente por serem comuns e passarem por uma cultura popular de que a medicina botânica e tao eficaz quanto outras. Por tanto, como problema de pesquisa, o presente artigo tende a refletir sobre: como a informacao sobre a acao de plantas medicinais pode contribuir para o tratamento e cuidados primarios de alguns casos de patologias? Atrelando a esta, o objetivo geral tende a: realizar um estudo etnobotânico sobre o uso de plantas medicinais como tratamento e cuidados primarios em alguns casos no sitio Frexeira Velha, evidenciando quais sao as plantas mais utilizadas pela populacao. Sobre os objetivos especificos, este por vez tende a: conceituar o que sao plantas medicinais; apontar o uso das plantas medicinais; relatar atraves de entrevista as plantas mais utilizadas na zona rural de Frexeira Velha, municipio de Pesqueira-PE. Sobre a metodologia utilizada, esta se da sobre a revisao de literatura, do tipo descritiva e exploratoria. A escolha por esse tipo de abordagem em pesquisa, surge com o interesse de entender a acao de plantas medicinais e a sua contribuicao para o tratamento e cuidados primarios de alguns casos patologias. Resultados e discussao, a utilizacao e a eficacia da planta medicinal passam muita credibilidade para quem faz a terapeutica e repassa os seus resultados. Conclusao: diante de bons resultados, mais pessoas sao impulsionadas ao uso das plantas medicinais, essas que acabam repassando essas experiencias para seus conhecidos e de geracao em geracao.

Background: Six to 20% of thyroid cancer (TC) patients develop distant metastases, and one-third become radioiodine refractory (RAIR). Available targeted therapies increase progression-free surviva...

Background: Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms. Materials and Methods: Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000. Results: Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8. Conclusions: A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25–82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigateTERTpromoter mutations. The genetic landscape of all paired sites comprisedBRAF,NRAS,HRAS,TP53,ATM,MUTYH,POLE, andNTRKgenes, includingBRAFandNTRKfusions.BRAFV600E was the most common point mutation in the paired specimens (5/12).TERTpromoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

Background and Objective The brain is an unusual site for distant metastases of differentiated thyroid carcinoma (DTC). The aim of this study was to document the prevalence of brain metastases from DTC at our institutions and to analyze the current therapies and the outcomes of these patients. Methods We performed a retrospective chart review of patients with DTC and secondary neoplasia of the brain. Results From 2002 to 2016, 9514 cases of thyroid cancer were evaluated across our institutions and 24 patients met our inclusion criteria, corresponding to a prevalence of 0.3% of patients with DTC. Fourteen (58.3%) were female and 10 (41.7%) were male. Fifteen patients had papillary thyroid cancer (PTC) (62.5%). Brain metastases were diagnosed 0 to 37 years (mean ± SD, 10.6 ± 10.4 years) after the initial diagnosis of thyroid cancer. Patients undergoing surgery had a median survival time longer than those that did not undergo surgery (27.3 months vs 6.8 months; P = 0.15). Patients who underwent stereotactic radiosurgery (SRS) had a median survival time longer than those that did not receive SRS (52.5 months vs 6.7 months; P = 0.11). Twelve patients (50%) were treated with tyrosine kinase inhibitors (TKIs), and they had a better survival than those who have not used a TKI (median survival time, 27.2 months vs 4.7 months; P < 0.05). Conclusion The prevalence of brain metastases of DTC in our institutions was 0.3% over 15 years. The median survival time after diagnosis of brain metastases was 19 months. In our study population, the use of TKI improved the survival rates.

Struma ovarii is a rare ovarian teratoma predominantly composed of thyroid tissue. The simultaneous presence of thyroid carcinoma in the struma ovarii and the thyroid gland is extremely rare. It remains unclear if these carcinomas represent independent primary tumors and whether the molecular mechanisms of the tumors developing in the thyroid and ovarian tissues are similar. We present the case of a patient with two independent papillary thyroid carcinomas (PTCs) in struma ovarii and the thyroid gland that are driven by different RAS mutations. A 62-year-old woman with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was diagnosed with a pelvic mass during a CT scan. She had surgery that included removal of her ovaries. A 7.2-cm classical variant of PTC arising in a struma ovarii was identified in the right ovary. Two months after the pelvic surgery, total thyroidectomy was performed, and a small nodule (0.8 cm) in the left lobe was diagnosed as a classical variant of PTC. Molecular analysis of tissues obtained from both the malignant struma ovarii and thyroid gland was performed. RAS mutations both in the PTC located in the thyroid and ovarian tissues were identified. However, whereas the thyroid gland tumor showed an HRAS Q61R mutation, the PTC in struma ovarii harbored an NRAS Q61R mutation. In this case, the finding of distinct types of RAS point mutation in thyroid cancers at two different locations provides definitive evidence that these cancers are synchronously developed independent primary tumors., We present the case of a patient with two independent papillary thyroid carcinomas in struma ovarii and the thyroid gland that are driven by different RAS mutations.

Four decades after reverse T3 (3,3′5′-triiodothyronine) was discovered, its physiologic and clinical relevance remains unclear and is still being studied. But scientific uncertainty has not stopped writers in the consumer press and on the Internet from making unsubstantiated claims about this

Background: Whether radioactive iodine ((131)I) treatments for differentiated thyroid cancer should be performed as an outpatient or inpatient remains controversial. The objective of this study was to survey selected aspects of radiation safety of patients treated with (131)I for differentiated thyroid cancer as an outpatient. Methods: An e-mail invitation was sent to over 15,000 members of ThyCa: Thyroid Cancer Survivors' Association, Inc. to complete a web-based survey on selected aspects of radiation safety regarding their last outpatient (131)I treatment. Results: A total of 1549 patients completed the survey. Forty-five percent (699/1541) of the respondents reported no discussion on the choice of an inpatient or outpatient treatment. Moreover, 5% (79/1541) of the respondents reported that their insurance company made the decision. Survey respondents recalled receiving oral and written radiation safety instructions 97% (1459/1504) and 93% (1351/1447) of the time, respectively. Nuclear medicine physicians delivered oral and written instructions to 54% (807/1504) and 41% (602/1462) of the respondents, respectively. Eighty-eight percent (1208/1370) of the respondents were discharged within 1 hour after receiving their (131)I treatment, and 97% (1334/1373) traveled in their own car after being released from the treating facility. Immediately post-therapy, 94% (1398/1488) of the respondents stayed at their own home or a relative's home, while 5% (76/1488) resided in a public lodging. The specific recommendations received by patients about radiation precautions varied widely among the respondents. Ninety-nine percent (1451/1467) of the respondents believed they were compliant with the instructions. Conclusion: This is the largest, patient-based survey published regarding selected radiation safety aspects of outpatient (131)I treatment. This survey suggests several concerns about radiation safety, such as the decision process regarding inpatient versus outpatient treatment, instructions about radiation safety, transportation, and lodging after radioiodine therapy. These concerns warrant further discussion, guidelines, and/or policies.

We examined the utility of microfluidic digital PCR (dPCR) for detection of BRAF and TERT mutations in thyroid tumors. DNA extracted from 100 thyroid tumors (10 follicular adenomas, 10 follicular cancers, 5 medullary cancers, and 75 papillary thyroid cancer (PTC) were used for detection of BRAF and TERT mutations. Digital PCRs were performed using rare mutation SNP genotyping assays on QuantStudio 3D platform. In PTCs, BRAFV600E was detected by dPCR and Sanger sequencing in 42/75 (56%) and in 37/75 (49%), respectively. BRAFV600E was not detected in other tumors. The ratio of mutant/total BRAF alleles varied from 4.7% to 47.5%. These ratios were higher in classical PTCs (27.1%) as compared to follicular variant PTCs (9.4%) p = 0.001. In PTCs with and without metastases, the ratios of mutant/total BRAF alleles were 27.6% and 18.4%, respectively, (p = 0.03). In metastatic lesions percentages of mutant/total BRAF alleles were similar to those detected in primary tumors. TERTC228T and TERTC250T were found in two and one cases, respectively, and these tumors concomitantly harbored BRAFV600E. These tumors exhibited gross extra-thyroidal extension, metastases to lymph nodes, and pulmonary metastases (one case). Our results showed that dPCR allows quantitative assessment of druggable targets in PTCs and could be helpful in a molecular-based stratification of prognosis in patients with thyroid cancer.

7025 Background: ICPi cause various irAE with thyroid dysfunction as a commonly reported abnormality. There is increasing evidence showing positive association with development of irAE and survival. However, prior trials with ICPi had underrepresentation of minorities with

Patients presenting with a thyroid nodule are common in the clinical practice of endocrinologists, even for those who are not thyroidologists. When seeing a patient with a thyroid nodule, the question that typically occurs first is whether the nodule could be malignant and how can the diagnosis be most efficiently and accurately determined. Then, once a diagnosis of cancer might be confirmed, and discussion turns to details about management, the next prominent question in the patient’s mind relates to their [...]

e14096 Background: Immune checkpoint inhibitors (ICPi) have emerged as an effective treatment for a variety of cancers. However, important immune-related adverse events (irAEs) can occur. The aim of this study was to determine the prevalence of endocrine irAEs in patients with head and neck cancer and lung cancer that have used a ICPi and outcomes. Methods: A systematic literature review was performed within PubMed and EMBASE databases. Search terms included “durvalumab”, “atezolizumab”, “nivolumab”, “pembrolizumab”, “ipilimumab”, “head & neck cancer”, “lung cancer”. Studies published before September 2018 were included. The search was limited to randomized controlled trials (RCTs) phase III written in English. Data were extracted about patient characteristics, interventions, overall survival (OS), progression free survival (PFS), and endocrine irAEs. A summary hazard ratio (HR) and 95% confidence interval were calculated using the software Comprehensive Meta-Analysis and a scatter plot was generated. Results: Twelve RCTs comprising 7060 patients were reviewed; 3815 used an ICPi (treatment arm). The mean follow-up time of 12.2 months ± 7.1 SD. The survival rate of the treatment arm was enhanced (HR, 0.75; 95% CI, 0.70-0.80), compared to the alternate arm. Similarly, the PFS of the treatment arm was improved (HR, 0.77; 95% CI, 0.72-0.81) but with a higher incidence of endocrine irAEs. The most common endocrine irAE reported was hypothyroidism;193 patients in the treatment arm vs. 29 in the alternate arm (p < 0.001); grade 3/4 AE was observed in 10 patients vs. 1 patient, respectively. Other endocrine irAEs were reported in 168 patients in the treatment arm vs. 26 patients in the alternate arm (p < 0.001); grade 3/4 AE was observed in 28 patients vs. 3 patients, respectively. A significant positive correlation between endocrine irAEs and OS was observed (p = 0.019). Conclusions: ICPi are a powerful tool in the treatment of cancer. The prevalence of endocrine irAEs in this meta-analysis was 9%. There is evidence of improved overall survival in patients who developed endocrine irAEs. Further studies are needed to correlate the development of irAEs and OS advantage.

Importance Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. Objective To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Design, Setting, and Participants Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. Interventions A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). Main Outcomes and Measures The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Results Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. Conclusions and Relevance In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.