Dihydrotanshinone I exhibits antitumor effects via ß-catenin downregulation in papillary thyroid cancer cell lines.

Thyroid cancer is the most common endocrine carcinoma and, among its different subtypes, the papillary subtype (PTC) is the most frequent. Generally, PTCs are well differentiated, but a minor percentage of PTCs are characterized by a worse prognosis and more aggressive behavior. Phytochemicals, naturally found in plant products, represent a heterogeneous group of bioactive compounds that can interfere with cell proliferation and the regulation of the cell cycle, taking part in multiple signaling pathways that are often disrupted in tumor initiation, proliferation, and progression. In this work, we focused on 15,16-dihydrotanshinone I (DHT), a tanshinone isolated from Salvia miltiorrhiza Bunge (Danshen). We first evaluated DHT biological effect on PTC cells regarding cell viability, colony formation ability, and migration capacity. All of these parameters were downregulated by DHT treatment. We then investigated gene expression changes after DHT treatment by performing RNA-seq. The analysis revealed that DHT significantly reduced the Wnt signaling pathway, which plays a role in various diseases, including cancer. Finally, we demonstrate that DHT treatment decreases protein levels of ß-catenin, a final effector of canonical Wnt signaling pathway. Overall, our data suggest a possible use of this nutraceutical as an adjuvant in the treatment of aggressive papillary thyroid carcinoma.

Anti-papillary thyroid carcinoma effects of dioscorea bulbifera L. through ferroptosis and the PI3K/AKT pathway based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer with a rising global incidence. Despite favorable prognoses, a significant recurrence rate persists. Dioscorea bulbifera L. (DBL), a traditional Chinese medicine, has been historically used for thyroid-related disorders. However, its therapeutic effects and mechanisms of action on PTC remain unclear. AIM OF THE STUDY: To explore the potential therapeutic effects, principal active components, and molecular mechanisms of DBL in the treatment of PTC through network pharmacology and molecular docking, with experimental validation conducted to corroborate these findings. MATERIALS AND METHODS: The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was utilized as a systematic tool for collecting and screening the phytochemical components of DBL, and for establishing associations between these components and molecular targets. Based on this, network data was visually processed using Cytoscape software (version 3.8.0). Concurrently, precise molecular docking studies of the principal active components of DBL and their corresponding targets were conducted using Autodock software. Additionally, PTC-related genes were selected through the GeneCards and GEO databases. We further employed the DAVID bioinformatics resources to conduct comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the intersecting genes between DBL and PTC. These analyses aid in predicting the potential therapeutic actions of DBL on PTC and its mechanisms of action. To validate these findings, corresponding in vitro experimental studies were also conducted. RESULTS: In this investigation, 14 bioactive compounds of DBL and 195 corresponding molecular targets were identified, with 127 common targets shared between DBL and PTC. Molecular docking revealed strong binding affinities between major bioactive compounds and target proteins. GO enrichment analysis unveiled key processes involved in DBL's action. KEGG analysis highlighted DBL's modulation of the PI3K/AKT signaling pathway. Experimental outcomes demonstrated DBL's potential in inhibiting PTC cell proliferation and migration, suppressing PI3K/AKT pathway activation, and promoting ferroptosis. CONCLUSION: In conclusion, DBL offers a multifaceted therapeutic approach for PTC, targeting multiple molecular entities and influencing diverse biological pathways. Network pharmacology and molecular docking shed light on DBL's potential utility in PTC treatment, substantiated by experimental validation. This study contributes valuable insights into using DBL as a promising therapeutic agent for PTC management.

Targeting Nrf2 to treat thyroid cancer.

Oxidative stress (OS) is recognized as a contributing factor in the development and progression of thyroid cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor involved in against OS generated by excessive reactive oxygen species (ROS). It governs the expression of a wide array of genes implicated in detoxification and antioxidant pathways. However, studies have demonstrated that the sustained activation of Nrf2 can contribute to tumor progression and drug resistance in cancers. The expression of Nrf2 was notably elevated in papillary thyroid cancer tissues compared to normal tissues, indicating that Nrf2 may play an oncogenic role in the development of papillary thyroid cancer. Nrf2 and its downstream targets are involved in the progression of thyroid cancer by impacting the prognosis and ferroptosis. Furthermore, the inhibition of Nrf2 can increase the sensitivity of target therapy in thyroid cancer. Therefore, Nrf2 appears to be a potential therapeutic target for the treatment of thyroid cancer. This review summarized current data on Nrf2 expression in thyroid cancer, discussed the function of Nrf2 in thyroid cancer, and analyzed various strategies to inhibit Nrf2.

A Misleading Case of NTRK-Rearranged Papillary Thyroid Carcinoma.

Herein, we present a misleading case of advanced papillary thyroid carcinoma with lung, node, and pleural metastases, initially diagnosed as metastatic lung adenocarcinoma with papillary features, based on the histological and immunohistochemical analysis of a pleural biopsy. Between August 2019 and August 2020, the patient received 2 ineffective lines of systemic therapy, including a first line of chemotherapy with cisplatin and pemetrexed, and a second line of immunotherapy with atezolizumab. Comprehensive genomic profiling by next-generation sequencing on the archival pleural biopsy revealed an NTRK1-TMP3 fusion and comutation of the TERT promoter, commonly found in papillary thyroid carcinoma. After palliative partial thyroidectomy that confirmed the diagnosis of papillary thyroid carcinoma, in February 2021, the patient was enrolled in the STARTRK-2 GO40782 basket trial and received entrectinib, an oral pan-TRK inhibitor specifically targeting NTRK-rearranged tumors. After initially experiencing drug-related grade 2 anorexia, dysgeusia, and neurotoxicity and grade 3 asthenia, the dose was reduced, and an excellent and durable objective response was observed.

Hyperbranched polyamidoamine-RGD peptide/si-circICA1 in the treatment of invasive thyroid cancer through targeting of the miR-486-3p/SERPINA1 axis.

Aim: This study aimed to identify molecular markers associated with papillary thyroid cancer (PTC) and investigate the therapeutic potential of targeted nanoscale drugs. Materials & methods: We analyzed the effects of circICA1 and miR-486-3p on B-CPAP cells' proliferation, apoptosis, migration and invasion. The regulation of the miR-486-3p/SERPINA1 axis was explored using quantitative real-time reverse transcription PCR and western blot analyses for metastasis. In vivo, we evaluated the effects of hyperbranched polyamidoamine-RGD peptide/si-circICA1 on PTC growth and metastasis. Results: Enhanced miR-486-3p expression inhibits B-CPAP cells' proliferation and invasion. si-circICA1 delivered via hyperbranched polyamidoamine-RGD peptide nanoparticles shows potential for treating metastasis in PTC. Conclusion: This study identifies key molecular mechanisms underlying PTC invasiveness and suggests a promising therapeutic strategy for PTC using targeted nanoscale drugs.

Neoadjuvant dabrafenib and trametinib for functional organ preservation in recurrent BRAF V600E-mutated papillary thyroid cancer.

OBJECTIVES: To describe the first reported use of neoadjuvant dabrafenib and trametinib specifically to permit organ conservation surgery in locally advanced recurrent differentiated thyroid carcinoma. PATIENTS AND METHODS: A patient presented with locally recurrent, radioiodide-resistant DTC with a BRAF V600E mutation invading the laryngotrachea. Definitive treatment would require a total laryngectomy. She was offered neoadjuvant dabrafenib and trametinib prior to surgery. RESULTS: A significant radiographic response permitted partial laryngectomy, enabling preservation of voice, early resumption of oral feeding, and avoidance of permanent tracheostomy. At 9 months, she remained free of disease. CONCLUSION: Neoadjuvant tyrosine kinase inhibitor treatment prior to definitive surgery for locally-invasive recurrent DTC is a potential approach that may limit the degree of surgery and associated morbidity.

Discovery of New Anti-Cancer Agents against Patient-Derived Sorafenib-Resistant Papillary Thyroid Cancer.

Thyroid cancer is the most well-known type of endocrine cancer that is easily treatable and can be completely cured in most cases. Nonetheless, anti-cancer drug-resistant metastasis or recurrence may occur and lead to the failure of cancer therapy, which eventually leads to the death of a patient with cancer. This study aimed to detect novel thyroid cancer target candidates based on validating and identifying one of many anti-cancer drug-resistant targets in patient-derived sorafenib-resistant papillary thyroid cancer (PTC). We focused on targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA) in patient-derived sorafenib-resistant PTC cells compared with patient-derived sorafenib-sensitive PTC cells. We discovered novel SERCA inhibitors (candidates 33 and 36) by virtual screening. These candidates are novel SERCA inhibitors that lead to remarkable tumor shrinkage in a xenograft tumor model of sorafenib-resistant patient-derived PTC cells. These results are clinically valuable for the progression of novel combinatorial strategies that facultatively and efficiently target extremely malignant cancer cells, such as anti-cancer drug-resistant PTC cells.

Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is one of the most common endocrine carcinomas worldwide and the aetiology of this cancer is still not well understood. Therefore, it remains important to understand the disease mechanism and find prognostic biomarkers and/or drug candidates for PTC. Compared with approaches based on single-gene assessment, network medicine analysis offers great promise to address this need. Accordingly, in the present study, we performed differential co-expressed network analysis using five transcriptome datasets in patients with PTC and healthy controls. Following meta-analysis of the transcriptome datasets, we uncovered common differentially expressed genes (DEGs) for PTC and, using these genes as proxies, found a highly clustered differentially expressed co-expressed module: a 'PTC-module'. Using independent data, we demonstrated the high prognostic capacity of the PTC-module and designated this module as a prognostic systems biomarker. In addition, using the nodes of the PTC-module, we performed drug repurposing and text mining analyzes to identify novel drug candidates for the disease. We performed molecular docking simulations, and identified: 4-demethoxydaunorubicin hydrochloride, AS605240, BRD-A60245366, ER 27319 maleate, sinensetin, and TWS119 as novel drug candidates whose efficacy was also confirmed by in silico analyzes. Consequently, we have highlighted here the need for differential co-expression analysis to gain a systems-level understanding of a complex disease, and we provide candidate prognostic systems biomarker and novel drugs for PTC.

Case Report: Papillary thyroid carcinoma in Goltz-Gorlin syndrome.

Goltz-Gorlin syndrome (GGS), also known as focal dermal hypoplasia, is a rare X-linked disorder caused by pathogenic variants in the PORCN gene and characterized by several abnormalities, including skin and limb defects, papillomas in multiple organs, ocular malformations, and mild facial dysmorphism. To date, only approximately 300 cases have been described in the literature. A 16-year-old female patient, born with multiple congenital dysmorphisms consistent with GGS and confirmed by genetic exam, was referred to our outpatient clinic for the workup of a thyroid nodule. A thyroid ultrasound showed a bilateral nodular disease with a 17-mm large hypoechoic nodule in the right lobe. Cytological exam of fine needle aspiration biopsy was suspicious for malignancy. Thus, she underwent total thyroidectomy plus lymphadenectomy of the right central compartment. A histological exam disclosed a papillary thyroid carcinoma (PTC) with lymph node micrometastases. Radioiodine (131-Iodine) therapy was performed. At 3- and 6-month follow-up, the patient did not present either ultrasound or laboratory PTC recurrence. To our knowledge, we report the first case of PTC in a patient with GGS. Since thyroid cancer is rare among children and adolescents, we hypothesize that the PORCN pathogenic variant could be responsible for tumor susceptibility. We also provide an overview of the clinical findings on GGS patients already reported and discuss the possible pathogenetic mechanism that may underlie this rare condition, including the role of PORCN in tumor susceptibility.

Curcumin induces mitophagy by promoting mitochondrial succinate dehydrogenase activity and sensitizes human papillary thyroid carcinoma BCPAP cells to radioiodine treatment.

Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.

Sustained Response with Dose-reduced Selpercatinib in a Pediatric Patient with Metastatic NCOA4-RET Fusion Papillary Thyroid Carcinoma.

Understanding the molecular landscape of papillary thyroid carcinoma (PTC), the most common thyroid cancer in children, creates additional therapeutic approaches. RET gene rearrangements are observed in pediatric PTC, and selective inhibition of RET is now possible with specific tyrosine kinase inhibitors designed to target diverse RET -activating alterations. We present a 13-year-old female with metastatic PTC, clinically resistant to radioactive iodine, and found to harbor a NCOA4-RET fusion. She responded to selpercatinib treatment with the elimination of supplemental oxygen need, marked reduction in pulmonary nodules and mediastinal lymphadenopathy, and biomarker decline. The response was maintained despite 2 dose reductions for possibly related weight gain.

The effect of selenium supplementation on sonographic findings of salivary glands in papillary thyroid cancer (PTC) patients treated with radioactive iodine: study protocol for a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Thyroid cancer is a very damaging disease. The most common treatment for this disease includes thyroidectomy and then using radioactive iodine (RAI). RAI has many side effects, including a decrease in salivary secretions, followed by dry mouth and oral and dental injuries, as well as increased inflammation and oxidative stress. Selenium can be effective in these patients by improving inflammation and oxidative stress and by modulating salivary secretions. So far, only one clinical trial has investigated the effect of selenium on thyroid cancer patients treated with radioiodine therapy (RIT) conducted on 16 patients; considering the importance of this issue, to show the potential efficacy of selenium in these patients, more high-quality trials with a larger sample size are warranted. METHODS: This is a parallel double-blind randomized controlled clinical trial that includes 60 patients aged 20 to 65 years with papillary thyroid cancer (PTC) treated with RAI and will be conducted in Seyyed al-Shohada Center, an academic center for referral of patients to receive iodine, Isfahan, Iran. Thirty patients will receive 200 µg of selenium for 10 days (3 days before to 6 days after RAI treatment) and another 30 patients will receive a placebo for the same period. Sonographic findings of major salivary glands, salivary secretions, and sense of taste will be evaluated before and 6 months after 10-day supplementation. DISCUSSION: Due to its anti-inflammatory and antioxidant effects, as well as improving salivary secretions, selenium may improve the symptoms of thyroid cancer treated with radioactive iodine. In past studies, selenium consumption has not reduced the therapeutic effects of radiation therapy, and at a dose of 300 to 500 µg/day, it has not had any significant side effects in many types of cancer under radiation therapy. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201129049534N6 . Registered on 16 September 2021.

Histological findings of thyroid cancer after lenvatinib therapy.

AIMS: Lenvatinib is a multikinase inhibitor used for treating unresectable or metastatic cancers, including thyroid cancer. As total thyroidectomy followed by radioactive iodine therapy is a commonly recommended initial treatment for thyroid cancer, histological findings of the thyroid after lenvatinib therapy remain unclear. Therefore, the aim of this study was to analyse in-vivo changes in patients who underwent thyroidectomy after lenvatinib therapy. METHODS AND RESULTS: We screened 167 patients with thyroid cancer [papillary thyroid cancer (PTC), n = 102; follicular thyroid cancer (FTC), n = 26; anaplastic thyroid cancer (ATC), n = 39] who underwent lenvatinib therapy. Among these patients, six underwent thyroidectomy (lenvatinib-treated group: PTC, n = 3; FTC, n = 1; ATC, n = 2), and the specimens were examined. Five patients with PTC who did not receive lenvatinib therapy were included for comparison (untreated group). Microvessel density (MVD) was evaluated in both groups. The PTC and FTC specimens showed relatively more ischaemic changes than ATC specimens. Coagulative necrosis and ischaemic changes in cancer cells were frequently observed. ATC specimens showed fibrosis and mild cell damage. As hypothyroidism is a common side effect of lenvatinib therapy, non-cancerous thyroid tissues were also examined. Histological findings included mild lymphocytic infiltration, lymphoid follicular formation, histiocytic reaction and follicular epithelial destruction. The MVD in lenvatinib-treated tissues was significantly lower than that in untreated tissues. CONCLUSIONS: Lenvatinib therapy probably induces relatively specific ischaemic changes in thyroid cancer cells. Moreover, inflammatory cell infiltration and decreased MVD occur to varying degrees in non-cancerous thyroid tissue and may be related to hypothyroidism, a side effect of lenvatinib.

Real-world clinical profile, treatment patterns and patient-reported outcomes for thyroid cancer in Japan.

Aim: To provide a real-world snapshot of the clinical profile, management, and patient-reported outcomes (PRO) for advanced medullary and papillary thyroid cancer prior to the availability of rearranged during transfection (RET) inhibitors in Japan. Materials & methods: Physicians completed patient-record forms for eligible patients seen during routine clinical practice. Physicians were also surveyed about their routine practice and patients were asked to provide PRO data. Results: RET testing patterns varied by hospital type; no therapeutic relevance was a commonly cited reason to not carry out testing. Multikinase inhibitors were the main systemic therapies prescribed, although timing to start multikinase inhibitors varied; adverse events were reported as challenges. PROs revealed high disease/treatment burden. Conclusion: More effective and less toxic systemic treatment targeting genomic alterations is needed to improve long-term outcomes of thyroid cancer.

This survey, conducted in Japan in 2020, included doctors who treat thyroid cancer and their patients. It is called a real-world survey because it provides information such as the types of tests and treatments used for thyroid cancer management in everyday clinical practice. The survey focused on two types of thyroid cancer: papillary thyroid cancer (PTC), a common type, and medullary thyroid cancer (MTC), an uncommon type. About 10­20% of people with PTC and most people with MTC have alterations in a gene called RET, which caused the cancer. Laboratory tests can identify these gene alterations, fusions (joining the parts of two different genes) or mutations (changes to a gene's DNA sequence) and results can help guide treatment decisions. The survey showed that testing for RET gene alterations was less than optimal and varied by the type of hospital/center. Common reasons provided by doctors for not testing for RET alterations were, "no therapeutic relevance for patient management" and "specific targeted therapies not available". However, the survey was conducted before the availability in Japan of the treatment selpercatinib, which selectively targets/inhibits tumors with RET alterations. Most patients in the survey, including those with RET alterations, received treatment with a type of inhibitor called multikinase inhibitors, as per available guidelines. Doctors considered side effects due to inhibition of multiple targets by multikinase inhibitors to be among areas for improvement needed. People with PTC and MTC also reported substantial burdens (i.e., negative impact on their lives) from the disease/treatment. The researchers concluded that barriers to RET testing need to be overcome, and more effective and less toxic treatments targeting gene alterations are needed to improve long-term outcomes.

Factors Affecting Ablation Success After I-131 Radioactive Iodine Therapy in Low and Intermediate Risk Papillary Thyroid Cancer.

The study was to evaluate the effect of radioactive iodine (RAI) treatment application time and clinical, histopathological factors on ablation success in patients with operated papillary thyroid cancer (PTC) in low and intermediate-risk. One hundred sixty-one patients with PTC in the low and intermediate-risk were evaluated. Most patients (89.4%) were in the low-risk, and 10.6% were in the intermediate-risk. When the patients were divided into two groups according to the date of receiving RAI treatment after surgery, those who received early treatment (≤3 months) constituted the majority of the patients (72.7%). Seventeen patients received 1.85 Gigabecquerel (GBq), 119 3.7 GBq, 25 5.55 GBq RAI. Most patients (82%) achieved ablation success after the first RAI treatment. The time interval between surgery and RAI treatment did not affect ablation success. Stimulated Tg level measured on the RAI treatment day was an independent predictive factor for successful ablation (p<0.001). The cut-off value of Tg found to predict ablation failure was 5.86 ng/ml. It was concluded that 5.55 GBq RAI treatment could predict ablation success compared to 1.85 GBq dose (p=0.017). It was concluded that having a T1 tumor may predict treatment success compared to a T2 or T3 tumor (p=0.001, p<0.001, retrospectively). The time interval does not affect ablation success in low and intermediate-risk PTC. The ablation success rate may decrease in patients who receive low-dose RAI and have high Tg levels before treatment. The most crucial factor in achieving ablation success is giving enough doses of RAI to ablate the residual tissue.

Interleukin-6 promotes the dedifferentiation of papillary thyroid cancer cells.

Radioiodine treatment is a fundamental therapy for patients with papillary thyroid cancer (PTC). Sodium/iodide symporter (NIS)-mediated iodine uptake is a prerequisite for the efficacy of radioiodine therapy. Interleukin-6 (IL-6) is a pro-tumor cytokine, but its regulation of NIS expression in PTC has not been elucidated. In this study, we found that IL-6 enhanced the proliferation ability of PTC cells. Moreover, the negative association between IL-6 and NIS expression in thyroid cancer tissues was demonstrated. IL-6 downregulated thyroid-specific genes such as NIS, thyroid peroxidase, and thyroid-stimulating hormone receptor and thyroid-specific transcription factors including thyroid transcription factor-1 (TTF-1) and paired box protein-8 (PAX-8). The inhibitory effects of IL-6 on NIS expression were alleviated by mitogen-activated protein kinase and Janus kinase inhibitors. Depletion of c-Jun or STAT3 also rescued IL-6-induced NIS downregulation, with STAT3 depletion exerting a stronger effect. TTF-1 protein expression was also restored by depleting c-Jun or STAT3. STAT3 depletion, but not c-Jun depletion, alleviated the inhibitory effect of IL-6 on PAX-8 expression. Moreover, the downregulation of NIS by IL-6 was rescued by overexpressing TTF-1 and PAX-8. Tocilizumab, an IL-6 receptor blocker, did not have any cytostatic activity in PTC cells, and it also failed to induce redifferentiation in vitro. However, we found that the drug blocked the inhibitory effect of IL-6 on NIS expression. In summary, IL-6 inhibits NIS transcription in PTC cells by activating mitogen-activated protein kinase and Janus kinase signaling.

Antineoplastic properties of polyphenols in TPC-1 human papillary thyroid carcinoma cell line: a systematic review.

Thyroid cancer usually responds to surgical and ablative therapy, but when it's refractory the alternative lies in tyrosine kinase inhibitors that, in addition to harmful side effects, acts only in a palliative way. The concern for other therapeutic possibilities brought evidence on flavonoids, hypothesizing a possible strategy. This review aimed to organize a compilation of in vitro studies using polyphenol substances in TPC-1 (human papillary thyroid carcinoma cell line) summarizing it's results and describing the metabolic pathways involved. Articles were selected on PubMed, Google Scholar, LILACS, BVS and SciELO, using keywords "thyroid cancer", "flavonoids" and "TPC-1", until June 2022. 185 studies were selected. After identification and exclusion of duplicates and exclusion criteria applied, 11 original articles were evaluated. Of these, the findings of flavonoids added to TPC-1 were: inhibition of cell growth and viability, promotion of cell cycle arrest and induction of apoptosis. Polyphenolic compounds have antineoplastic properties by different mechanisms as shown in vitro, but the concentrations needed are above usual dietary consumption and the findings are limited to experimental cellular studies. Despite that, these results should be useful to guide further analysis aiming to reveal the real safety and efficacy of polyphenols in this scenario.

Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report.

A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

False-Positive Radioactive Iodine Uptake Caused by Cervical Myofascitis in a Patient With Differentiated Thyroid Carcinoma.

ABSTRACT: A 31-year-old woman with a history of papillary thyroid cancer underwent ablative 131I therapy. Posttherapeutic whole-body 131I scintigraphy revealed abnormally increased activity in the neck. Additional SPECT/CT images localized the activity in the bilateral peripheral fascia of the platysma.

Outpatient ablation treatment with two doses of 30 mCi of radioactive iodine for non-low-risk papillary thyroid cancer.

Outpatient ablation therapy with low-dose radioactive iodine (RAI) is applied to non-low-risk papillary thyroid cancer patients due to a chronic shortage of inpatient RAI treatment wards in Japan. We used the maximum dosage available for outpatient therapy of 30 mCi of RAI for ablation and diagnostic (Dx) whole-body scintigraphy (WBS). This study aimed to examine the significance of the second dose of 30 mCi. DxWBS was performed 6 months after ablation, and assessment of success or failure was performed 12 months after ablation. A second WBS was performed in the remaining RAI accumulation cases in the neck on DxWBS. The criteria for successful ablation was negative cervical accumulation on WBS, thyroid stimulating hormone-suppressed thyroglobulin (sup-Tg) below 1.0 ng?/?mL, and no increase in thyroglobulin antibody (TgAb) level. At the time of DxWBS, 35?/?68 cases met the successful criteria, and 45 cases achieved success at assessment. Sup-Tg values decreased significantly after ablation and decreased further after DxWBS in successful ablation cases, whereas those were not changed in ablation failure cases. Findings indicated that RAI used in DxWBS had therapeutic effects. It makes sense to use 30 mCi for DxWBS, given the current difficulty of inpatient ablation therapy with high-dose RAI. J. Med. Invest. 70 : 17-21, February, 2023.