Real-World Use of Systemic Therapies for the Treatment of Advanced Thyroid Cancers.

OBJECTIVE: In the last decade, new systemic treatment options have been made available for patients with advanced thyroid cancer. However, little is known about the real-world utilization of these systemic therapies. METHODS: We used Optum's de-identified Clinformatics® Data Mart Database to characterize trends in the use of 15 systemic therapies that are available for the treatment of advanced thyroid cancer between 2013 and 2021. Joinpoint regression was used to calculate annual percentage changes in the use of systemic therapy by patients' race/ethnicity. The sequence of therapies was determined by the date of prescription claims. RESULTS: Between 2013 and 2021, the annual number of patients treated for advanced thyroid cancer with systemic therapy increased from 45 patients in 2013 to 114 patients in 2021 (N of total cohort = 885). Most patients were female (54.7%) and non-Hispanic White (62.1%). Between 2013 and 2021, there was a significant decrease in the proportion of non-Hispanic White patients treated for advanced thyroid cancer with systemic therapy (annual percentage change -3.9%, 95% confidence intervals, -6.0% to -1.8%). Since its approval by the US Food and Drug Administration (FDA) in 2015, lenvatinib remains the most frequently prescribed first-line therapy for the treatment of radioiodine-refractory thyroid cancer (48.8% of patients between 2017 and 2021). Between 2017 and 2021, most patients (79.7%) were initiated on 1 of the 10 FDA-approved agents and 81.7% received only a first-line therapy. CONCLUSIONS: Between 2013 and 2021, the use of systemic treatment options for advanced thyroid cancer increased significantly, largely driven by the prescription of lenvatinib following its approval by the FDA in 2015, with an increasing trend for use in non-White patients.

Management of patients with extensive locally advanced thyroid cancer: results of multimodal treatments.

PURPOSE: Surgery plays a key role in the treatment of thyroid cancer (TC) patients. Locally advanced cases, however, can require an extensive surgical approach with technical issues and a high risk of complications. In these cases, a multidisciplinary evaluation should be carried out to evaluate pros and cons. The aim of this study was to share our experience, as a multidisciplinary team, in the management of patients with locally advanced TC with a particularly extensive local disease, whose surgical approach could be challenging and part of a multimodal treatment. METHODS: We retrospectively evaluated clinical, surgical, and oncologic features of all patients with locally advanced TC who had undergone multidisciplinary surgery from January 2019 to June 2020. RESULTS: Six patients (two cases each of poorly differentiated, papillary, and medullary TC) were included. Four out of six were suffering from symptoms related to the advanced disease. At pre-surgical evaluation, a multidisciplinary team proposed extended surgery with radical intent via cervicotomy and sternotomy, considering other therapies not feasible or probably ineffective without it. No one passed away in intra- or perioperative time. At the end of follow-up (median 2.6 years), all patients presented a remission of symptoms due to the advanced disease, four patients were submitted to adjuvant therapies and only one patient died for a cause unrelated to the disease. CONCLUSION: This series of very advanced TCs shows the effectiveness of a surgery performed by a multidisciplinary team in controlling symptoms, allowing adjuvant therapies, and improving the survival of patients whose cases would otherwise be very difficult to manage.

Clinical outcomes of a cohort of 271 patients with lung metastases from differentiated thyroid carcinoma.

CONTEXT: Lung is the most common site of distant metastases from differentiated thyroid carcinoma (DTC). OBJECTIVE: To investigate the outcomes of a cohort of patients with DTC and lung metastases (LM). METHODS: A retrospective analysis of a cohort of 271 patients with LM was performed. RESULTS: The female-to-male ratio was 1:1 and the median follow-up time was 5.9 (1.1-38.4) years. Papillary thyroid carcinoma (PTC) was the most frequent type (83.4%), mainly the classic variant, followed by follicular thyroid carcinoma (FTC, 10.3%) and Hürthle cell carcinoma (HTC, 6.3%). The prevalence of PTC, FTC and HCC was different between the micronodular and macronodular LM groups [87.4%, 6.3% and 6.3% vs. 74.6%, 19.0% and 6.3%, respectively (p = .013)]. Only 5.0% of the patients had LM diagnosed after a period of remission. LM were submitted to radioactive iodine treatment (RAIT) in 84.5% (52.8% showed 131 iodine avid metastases). Complete remission was only achieved in 12.2%. Micronodular disease and age <55 years at LM diagnosis were associated with a better prognosis (p < .05). We found no difference in survival between patients with LM treated or not with RAIT. However, in patients submitted to RAIT, there was a tendency for longer survival in the group of patients with 131 I avid lesions. CONCLUSION: The classic variant of PTC was the most frequent histology found in LM of DTC. LM are rarely diagnosed in the follow-up when complete remission is achieved after surgery and 131 I. Younger age at LM diagnosis and a micronodular pattern are associated with a better prognosis.

Thyroid tumors at the limit of operability.

Comprehensive information about current thyroid carcinoma treatment options depending on its histology and extent of the disease, focusing on locally advanced findings at the limit of operability. Treatment of such a heterogeneous group requires interdisciplinary cooperation. We provide 6 unique case reports including imaging scans, description of the therapy and description of development of the condition.

Management of one patient with oligoprogressive thyroid cancer during treatment with lenvatinib.

Recent thyroid cancer guidelines found it reasonable to use local therapies during treatment with tyrosine kinase inhibitors (TKIs) in selected patients with oligoprogressive disease, namely, in the presence of a single progressing lesion in an otherwise TKI-responsive metastatic cancer. However, there is a lack of experience in the management of oligoprogressive thyroid cancers. This report illustrates the case of one patient with oligoprogressive thyroid cancer during therapy with lenvatinib. We found that the application of local ablative therapy in oligoprogressive disease prolonged the progression-free survival and thus extended the time to therapy interruption. However, the optimal care for TKI-treated oligoprogressive cancers remains unclear and needs to be investigated in prospective trials.

Neoadjuvant therapy to improve resectability of advanced thyroid cancer: A real-world experience.

BACKGROUND: Experience with targeted neoadjuvant treatment for locoregionally advanced thyroid cancer is nascent. METHODS: Multicenter retrospective case series examining targeted neoadjuvant treatment for locoregionally advanced thyroid cancer. The primary outcome was change in surgical morbidity as measured by two metrics developed for use in clinical trials to characterize surgical complexity and morbidity. Secondary outcomes included percentage of patients proceeding to surgery and percentage receiving an R0/R1 resection. RESULTS: Seventeen patients with varied molecular alterations, pathologies, and treatment regimens were included. Mean surgical complexity scores decreased between time points for baseline and postneoadjuvant treatment, postneoadjuvant treatment and surgery, and between baseline and surgery. Eleven patients (64.7%) underwent surgical resection, with 10 (58.8%) receiving an R0/R1 resection. CONCLUSIONS: Neoadjuvant treatment of advanced thyroid cancer improves resectability and decreases the morbidity of required surgical procedures. However, treatment is not uniformly effective.

Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience.

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.

Symptom clusters of patients with advanced thyroid cancer: a cross-sectional study.

PURPOSE: To investigate and analyze the symptom clusters of patients with advanced thyroid cancer and provide a basis for developing targeted symptom management measures. METHODS: Patients who visited a multidisciplinary outpatient service for advanced thyroid cancer at a tertiary A hospital in Sichuan Province from April 2022 to April 2023 were selected using convenience sampling. A cross-sectional survey was conducted using the M.D. Anderson Symptom Inventory-Thyroid Cancer module (MDASI-THY). Symptom clusters were extracted by exploratory factor analysis. RESULTS: Disturbed sleep had the highest incidence (75.7%) and severity (3.0 points), while mood distress had the highest incidence (63.5%) and severity (2.0 points) of symptom interference. Three symptom clusters were identified: mood-fatigue-sleep, digestive tract-sensation, and thyroid cancer-specific symptom clusters. CONCLUSION: Patients with advanced thyroid cancer have multiple symptom clusters that seriously affect their daily lives. Health care professionals should conduct targeted observation and preventive treatment to reduce the burden of symptoms on patients.

Pemetrexed-carboplatin salvage therapy in advanced thyroid cancers.

BACKGROUND: The overall survival of patients with advanced thyroid cancers that have progressed following targeted therapies is limited, indicating a strong need for salvage treatments. METHODS: We retrospectively analyzed patients with refractory advanced thyroid cancer treated with pemetrexed-carboplatin (PC) at Mayo Clinic since 2019. RESULTS: Eleven patients, three with anaplastic thyroid cancer (ATC), seven with differentiated or poorly differentiated thyroid cancer (DTC), and one with oncocytic carcinoma of the thyroid, were treated with novel salvage PC. Patients with DTC (n = 7) had durable responses with a median progression-free survival of 29 months. One responder included a patient with ATC whose disease progressed following pembrolizumab/axitinib, lenvatinib, and dabrafenib/trametinib. On this fourth line treatment, the patient remains on therapy to date, over 12 months after initial response. CONCLUSIONS: This case series reinforces prior published phase I clinical trial data and shows that pemetrexed can have potent efficacy in the treatment of the most advanced thyroid cancers.

Neoadjuvant Treatment in Locally Advanced Thyroid Carcinoma.

Although the focus in the last decades has been on the overdiagnosis of incidentally detected thyroid carcinomas in early stages, the other extreme of the disease is represented by locally advanced tumors with the invasion of neighboring structures. These are infrequent tumors, but they have a high complexity and a poor prognosis. In the absence of effective therapies allowing preoperative tumor reduction, in order to achieve a more restricted surgery, treatment was limited to aggressive surgery with resection of the aerodigestive tract and major vascular structures or palliative treatment. However, due to the increased knowledge of tumor biology and the results that tyrosine kinase inhibitors have achieved in the treatment of radioactive iodine-refractory tumors, neoadjuvant therapy with a curative intent has emerged as a reality to be taken into account when dealing with these patients. This paper presents a narrative review of the current scientific evidence regarding neoadjuvant treatment in locally advanced thyroid cancer.

Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients.

Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P < 0.05), with CSS of 82.0 % and 49.0 %, and OS of 70.6 % and 40.0 %, respectively. Cox regression analyses showed that age at diagnosis, tumor diameter, presence of DM, extrathyroidal extension sites, histological type, thyroidectomy scope, radiotherapy status, and chronological sequence of radiotherapy and surgery were observably correlated with CSS in LATC patients, and in addition to the above factors, gender, marital status, and chemotherapy status were also observably correlated with OS in LATC patients. The prognostic predictive power of the above factors is visualized by the Kaplan-Meier survival curve. The concordance index of nomograms for CSS and OS were 0.933, 0.925, and 0.926 (CSS), 0.918, 0.909, and 0.906 (OS), respectively, and the time-dependent receiver operating characteristic curve, area under curve, calibration curve and decision curve analysis curve indicate that the nomograms have good discriminatory ability, accuracy and clinical applicability in both the training and validation groups. Conclusions: In these findings, we drawed a conclusion that there were significant differences in clinical information between patients with T4a and T4b LATC, and we established and validated the first prognostic nomograms and risk stratification of CSS and OS for LATC patients at 3, 5, and 10 years, which will help clinicians to individualize their postoperative treatment and individualized follow-up.

Primary Intrathoracic Ectopic Papillary Thyroid Carcinoma, Presenting With Thoracic Spine Metastasis: A Case Presentation and Literature Review.

Thyroid cancer in ectopic thyroid tissue is a very rare entity. We report a patient with papillary thyroid cancer arising from upper mediastinal ectopic thyroid tissue. The patient presented with thoracic spine metastasis with cord compression. The patient was a 67-year-old woman, who presented with upper back pain. Magnetic resonance imaging (MRI) showed suspected metastatic disease in the second and third thoracic vertebrae (T2 and T3). She underwent laminectomy and decompression surgery at the T1-T3 level. The final pathology report showed metastatic thyroid carcinoma with papillary features. She underwent external beam radiation to the affected spine. Computerized tomography (CT) scan of the chest, abdomen, and pelvis showed a 3.0 × 2.8 × 2.3 cm soft-tissue mass in the left superior mediastinum extending into the supraclavicular region. Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed hypermetabolic foci in the upper mediastinum. Fine needle aspiration (FNA) of the upper mediastinal mass was consistent with papillary thyroid cancer. Molecular testing from the FNA sample using Thyroseq V3 showed SQSTM1NTRK3 chromosomal rearrangement. A total thyroidectomy was performed. Pathology of the resected thyroid was benign. Pathology of the mediastinal mass showed a papillary thyroid carcinoma with focal tall cell features, forming a 4 × 2.5 × 2.5 cm mass. Surgery was followed by ablation with 100 millicuries (mci) of radioactive iodine (I-131) and external beam radiation. This case highlights the presentation of primary intrathoracic papillary thyroid cancer with SQSTM1-NTRK3 chromosomal rearrangement and the challenges in the diagnosis and management of this unique case. This patient had a very aggressive disease presentation that required multimodal treatment, including thoracic spine decompression, total thyroidectomy, primary intrathoracic goiter resection, high-dose radioactive iodine treatment, and external beam radiation to the affected spine area. SQSTM1-NTRK3 chromosomal rearrangement can be targeted by medications such as larotrectinib and endtrectinib.

The Role of Pretherapy Quantitative Imaging and Dosimetry in Radioiodine Therapy for Advanced Thyroid Cancer.

Radioactive iodine is well established as a successful treatment for differentiated thyroid cancer (DTC), although around 15% of patients have local recurrence or develop distant metastases and may become refractory to radioactive iodine (RAI). A personalized approach to treatment, based on the absorbed radiation doses delivered and using treatments to enhance RAI uptake, has not yet been developed. Methods: We performed a multicenter clinical trial to investigate the role of selumetinib, which modulates the expression of the sodium iodide symporter, and hence iodine uptake, in the treatment of RAI-refractory DTC. The iodine uptake before and after selumetinib was quantified to assess the effect of selumetinib. The range of absorbed doses delivered to metastatic disease was calculated from pre- and posttherapy imaging, and the predictive accuracy of a theranostic approach to enable personalized treatment planning was investigated. Results: Significant inter- and intrapatient variability was observed with respect to the uptake of RAI and the effect of selumetinib. The absorbed doses delivered to metastatic lesions ranged from less than 1 Gy to 1,170 Gy. A strong positive correlation was found between the absorbed doses predicted from pretherapy imaging and those measured after therapy (r = 0.93, P < 0.001). Conclusion: The variation in outcomes from RAI therapy of DTC may be explained, among other factors, by the range of absorbed doses delivered. The ability to assess the effect of treatments that modulate RAI uptake, and to estimate the absorbed doses at therapy, introduces the potential for patient stratification using a theranostic approach. Patient-specific absorbed dose planning might be the key to more successful treatment of advanced DTC.

Clinical outcomes of combined cervical and transthoracic surgical approaches in patients with advanced thyroid cancer.

BACKGROUND: Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches. METHODS: Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015. RESULTS: Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and wound infection (13%). One-year overall survival was 84%; 1-year locoregional disease-free survival was 64%. Median time to locoregional recurrence was 36 months. Only esophageal invasion was associated with worse oncologic outcomes. CONCLUSIONS: Combined transcervical and transthoracic surgery for advanced thyroid cancer can be performed without mortality and with acceptable morbidity.

HHEX suppresses advanced thyroid cancer by interacting with TLE3.

Haematopoietically Expressed Homeobox (HHEX) gene is highly expressed in the thyroid gland and plays critical roles in the development and differentiation of the thyroid gland. While it has been indicated to be downregulated in thyroid cancer, its function and the underlying mechanism remain unclear. Herein, we observed low expression and aberrant cytoplasmic localization of HHEX in thyroid cancer cell lines. Knockdown of HHEX significantly enhanced cell proliferation, migration and invasion, while overexpression of HHEX showed the opposite effects in vitro and in vivo. These data provide evidence that HHEX is a tumor suppressor in thyroid cancer. Additionally, our results showed that HHEX overexpression upregulated the expression of sodium iodine symporter (NIS) mRNA and also enhanced NIS promoter activity, suggesting a favorable effect of HHEX in promoting thyroid cancer differentiation. Mechanistically, HHEX exerted a regulatory effect on the expression of transducin-like enhancer of split 3 (TLE3) protein, which inhibited the Wnt/ß-catenin signaling pathway. Nuclear localized HHEX bound to and upregulated TLE3 expression by preventing TLE3 protein from being distributed to the cytoplasm and being ubiquitinated. In conclusion, our study suggested that restoring HHEX expression has the potential to be a new strategy in the treatment of advanced thyroid cancer.

NTRK fusion events and targeted treatment of advanced radioiodine refractory thyroid cancer.

PURPOSE: Pathogenic fusion events involving neurotrophic receptor tyrosine kinase (NTRK) have been described in ~ 2% of differentiated thyroid cancer (DTC). The selective tropomyosin receptor kinase (TRK) inhibitors entrectinib and larotrectinib have been approved in a tumor agnostic manner based on phase 1/2 clinical trials. In a real-world setting at five referral centers, we aimed to describe the prevalence of NTRK gene fusions and the efficacy and safety of TRK inhibitor treatment for non-medullary, advanced thyroid cancer (TC). METHODS: A total of 184 TC patients with testing for NTRK gene fusions were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method in six patients with NTRK fusion-positive TC who underwent TRK inhibitor therapy. RESULTS: 8/184 (4%) patients harbored NTRK gene fusions. Six patients with radioiodine (RAI)-refractory TC harboring NTRK1 (n = 4) and NTRK3 (n = 2) gene fusions were treated with larotrectinib. Five patients (83%) had received ≥ 1 prior systemic therapy and one patient did not receive prior systemic therapy. All patients had morphologically progressive disease before treatment initiation. Objective response rate was 83%, including two complete remissions. Median PFS from start of TRK inhibitor treatment was 23 months (95% confidence interval [CI], 0-57.4) and median OS was not reached (NR) (95% CI, NR). Adverse events were of grade 1-3. CONCLUSION: The prevalence of NTRK gene fusions in our cohort of RAI-refractory TC is slightly higher than reported for all TC patients. Larotrectinib is an effective treatment option in the majority of NTRK gene fusion-positive advanced TC patients after prior systemic treatment and has a favorable safety profile.

Access Denied: Disparities in Thyroid Cancer Clinical Trials.

For thyroid cancer clinical trials, the inclusion of participants from diverse patient populations is uniquely important given existing racial/ethnic disparities in thyroid cancer care. Since 2011, a paradigm shift has occurred in the treatment of advanced thyroid cancer with the approval of multiple systemic therapies by the US Food and Drug Administration based on their use in the clinical trials setting. Although these clinical trials recruited patients from up to 164 sites in 25 countries, the inclusion of racial/ethnic minority patients remained low. In this mini-review, we provide an overview of barriers to accessing cancer clinical trials, framed in the context of why patients with thyroid cancer may be uniquely vulnerable. Multilevel interventions and increased funding for thyroid cancer research are necessary to increase access to and recruitment of under-represented patient populations into thyroid cancer clinical trials.

Clinico-pathological initial outcome of a newly adopted novel surgical technique for nodal metastatic thyroid cancer at a large-volume centre in a high-income developing country.

Introduction: Thyroid cancer is the most common tumour in the endocrine system. In the past decade, the incidence of lymph node metastasis has increased, and so has the patient demand for a smaller scar. This research reports the surgical and patho-oncological short-term outcomes of a novel, minimally invasive neck dissection approach for thyroid carcinoma with lymph node metastases at the UAE's leading endocrine surgery centre. Methods: This study employed a prospectively maintained surgical database to retrospectively analyse relevant parameters such as surgical complications, including bleeding, hypocalcaemia nerve injury and lymphatic fistula, as well as oncological metrics such as the type of tumour and the ratio of lymph node metastasis to the number of harvested lymph nodes in 100 patients that underwent open minimally invasive selective neck dissection. Results: The study comprised 50 patients with thyroidectomy, with bilateral central compartment neck dissection (BCCND; 50%); 34 with thyroidectomy, BCCND and selective bilateral lateral compartment neck dissection (BLCND; 34%); and 16 patients with selective unilateral central and lateral compartment neck dissection by recurrent nodal disease (ULCND; 16%). The female-to-male gender ratio was 78:22, with median ages of 36 and 42 years, respectively. Histopathology findings revealed that 92% of patients had papillary thyroid cancer (PTC) and 8% had medullary thyroid cancer. The mean total number of lymph nodes removed was 22 in the BLCND group, 17 in the ULCND group and 8 in the BCCND group (p = 0.001). Furthermore, the average lymph node metastasis was significantly higher in the BLCND group (p = 0.002). The percentage of temporary hypoparathyroidism was 29.8% and it persisted for 1.3%. The lateral compartment dissection morbidity was as follows: Four male patients with tall cell infiltrative PTC presented with pre-existing vocal cord paresis, necessitating nerve resection and anastomosis, and two more developed it after surgery (1.1% of the nerve at risk). Lymphatic fistulas occurred in four patients (4%) who were treated conservatively. Two patients were readmitted due to symptomatic neck collection. Horner syndrome was discovered in just one female patient. Male gender, aggressive histology and lateral compartment dissection independently increased surgical morbidity. In a high-volume endocrine centre, the adoption of minimally invasive selective neck dissections to treat nodal metastatic thyroid cancer did not increase specific cervical surgery complications.

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.

Circumferential Laryngotracheal Resection in Thyroid Cancer: Experience and Outcome in a Single Center.

There is limited experience of laryngotracheal resection in patients with differentiated thyroid carcinoma (DTC). The aim of this study was to report our experience of circumferential laryngotracheal resection in DTC and its long-term outcome. In this retrospective study, 10 patients of locally invasive DTC who underwent circumferential laryngotracheal resection between January 2000 and December 2015 were included. Clinicopathologic profile and follow up was noted. Mean age of the cohort was 50.1 ± 7.8 years (M:F = 1: 2.3). Papillary carcinoma was the commonest pathology (60%) followed by follicular carcinoma (20%), 10% each had Hurthle cell and poorly differentiated thyroid carcinoma. Sixty percent patients presented with recurrent or persistent disease and 20% with distant metastases. Vocal cord palsy was observed in 30%. Fifty percent patients underwent tracheal resection with end to end anastomosis and remaining laryngotracheal resection. Carotid artery resection and anastomosis was performed in one patient. Shin stage IV invasion was observed in 80% and stage III in remaining. There was no perioperative mortality. All patients received adjuvant radioiodine therapy and 40% external beam radiotherapy. Median follow up was 48 months. One patient who earlier had tracheal resection underwent total laryngectomy due to recurrent disease after 24 months. Forty percent patients developed distant metastases during follow-up. Mean survival was 77.8 months (CI = 63.0-92.5). Five-year overall survival was 60% and was significantly high in those without distant metastases (p = 0.006). The outcome of circumferential larygotracheal resections for DTC is excellent in terms of local disease control and long term survival.