Therapy For Differentiated Thyroid Cancer Research Articles

Real word outcomes of cabozantinib therapy in poorly differentiated thyroid carcinoma.

Poorly differentiated thyroid carcinomas (PDTCs) are rare and aggressive head and neck malignancies with a poor prognosis. Systemic treatment for incurable PDTC consists of multi-kinase inhibitors (MKIs) based on extrapolation from the experience with radioiodine refractory differentiated thyroid cancer (DTC). Cabozantinib is an approved second line MKI therapy for DTC, but there are limited data regarding safety and efficacy of cabozantinib for PDTC. We conducted a single institution, retrospective analysis of patients with PDTC who received cabozantinib in any line of therapy. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record. Median PFS and OS were primary endpoints and estimated using Kaplan-Meier methodology. Seven patients with PDTC who received cabozantinib, were included. 4/7 (57%) patients had a partial response to cabozantinib, while 2/7 (29%) had SD as their best response. Median time on treatment for cabozantinib was 10.53 months. Median PFS from start of cabozantinib was 12.9 months and median OS was 14.21 months. Most adverse events to treatment (5/6) were low grade. Two (29%) patients were alive at date of last follow up. Cabozantinib is an effective and reasonably well-tolerated treatment option for patients with PDTC. Prospective studies are needed to further investigate the role of cabozantinib in the treatment of PDTC, alone and in combination with other agents including checkpoint inhibitors.

Low dose radioactive iodine ablation therapy (1.11GBq) for differentiated thyroid cancer in Western Turkey

ObjectiveAblation therapy is employed in low-risk differentiated thyroid cancer (DTC) cases to facilitate patient monitoring by reducing thyroglobulin (Tg) levels to measurable levels below after surgery by eliminating residual thyroid tissue. However, there is still uncertainty about the minimum activity dose required for effective ablation. Opting for low-dose [131I]-NaI for ablation offers several advantages for both patients and healthcare services. Particularly in this tumor group with a high life expectancy (approximately 90–95 % at 10 years), [131I]-NaI treatment should not pose a risk to the patient's post-treatment life and should not compromise their quality of life. However, there is a need for a well-defined identification of factors predicting successful ablation. MethodsClinical data, laboratory findings, and imaging tests of 287 patients with low-dose 1110 MBq (30 mCi) [131I]-NaI ablation therapy for DTC were retrospectively reviewed. Post-ablation imaging and laboratory findings categorized ablation success/failure. The successful ablation group was determined according to the excellent response criteria outlined in ATA criteria. Relationships between clinical, pathological findings, biochemical common variables, and treatment failure were analyzed. ResultsAn excellent response was achieved in 77% of the entire group according to ATA criteria post-ablation. Male gender and high Tg levels on the day of ablation (Tg cut-off: 10 ng/mL and 5.35 ng/mL) were associated with unsuccessful ablation. ConclusionsOur results indicate that a 1110MBq (30mCi) ablation dose is sufficient to achieve an excellent response in most low-risk DTC cases 6–12 months later. When selecting the dose for ablation, besides the histological markers mentioned in guidelines and age, we observed that stimulated Tg values and gender may be important in predicting ablation success.

Update on lacrimal apparatus dysfunction associated with differentiated thyroid cancer after I-131 therapy.

The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC. A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were "Thyroid cancer", "I-131", "Complications", "Dry eye", "Epiphora", "Tear", "Nasolacrimal duct" and "NLDO". The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131. It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease.

Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients.

Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy.

Advanced RAI-refractory thyroid cancer: an update on treatment perspectives.

During the last decades, the knowledge on follicular cell-derived thyroid cancer molecular biology has led to the evolution of a number of novel therapies for these tumors, mainly tyrosine kinase inhibitors. Lenvantinib, sorafenib and recently cabozantinib have been approved for differentiated thyroid cancer (DTC), while larotrectinib and entrectinib for neurotrophic-tropomyosin receptor kinase-fusion thyroid cancer. For radioiodine (RAI) refractory DTCs ongoing research aims to identify agents that may restore RAI-avidity via redifferentiation protocols (vemurafenib or dabrafenib and trametinib) or combination treatments. These treatments are based on the tumor molecular signature. The treatment with targeted therapies has changed the therapeutic strategies and the disease prognosis, however drug resistance remains the main reason for treatment failure. Thus, the understanding of both molecular pathways implicated in tumorigenesis, and tumoral escape mechanisms, are of paramount significance for the development of new therapies for DTC. The present review focuses on the molecular landscape of DTC, the approved targeted therapies as well as the mechanisms of drug resistance. Furthermore, it points to the ongoing research and the future perspectives for the development of more efficient drugs for DTC.

CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer.

Chimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC). We undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using 3 previously described monoclonal antibodies, we generated 3 third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested preclinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice's physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T's safety. TSHR is highly and homogeneously expressed on 90.8% (138/152) of papillary thyroid cancer, 89.2% (33/37) of follicular thyroid cancer, 78.2% (18/23) of cervical lymph node metastases, and 86.7% of radioactive iodine resistance diseases. We developed 3 novel anti-TSHR CAR-Ts from monoclonal antibodies M22, K1-18, and K1-70; all 3 CAR-Ts mediate significant antitumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed. TSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with locoregional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.

2022 ETA Consensus Statement: What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer?

Modern use of post-operative radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) should be implemented in line with patients’ risk stratification. Although beneficial effects of radioiodine are undisputed in high-risk patients, controversy remains in intermediate-risk and some low-risk patients. Since the last consensus on post-surgical use of RAI in DTC patients, new retrospective data and results of prospective randomized trials have been published, which have allowed the development of a new European Thyroid Association (ETA) statement for the indications of post-surgical RAI therapy in DTC. Questions about which patients are candidates for RAI therapy, which activities of RAI can be used, and which modalities of pre-treatment patient preparation should be used are addressed in the present guidelines.

Management of Differentiated Thyroid Cancer: The Standard of Care.

In the past decade, the management of differentiated thyroid cancer (DTC) underwent a paradigm shift toward the use of risk stratification with the goal of maximizing the benefit and minimizing the morbidity of radioiodine (131I) therapy. 131I therapy is guided by information derived from surgical histopathology, molecular markers, postoperative diagnostic radioiodine scintigraphy, and thyroglobulin levels. 131I is used for diagnostic imaging and therapy of DTC based on physiologic sodium-iodine symporter expression in normal and neoplastic thyroid tissue. We summarize the essential information at the core of multidisciplinary DTC management, which emphasizes individualization of 131I therapy according to the patient's risk for tumor recurrence.

Association Between Body Mass Index and Aggressive Features of Differentiated Thyroid Cancer

Background: Obesity is recognized as a risk factor for several types of cancers, including differentiated thyroid cancer (DTC). However, the association between obesity and aggressiveness of DTC is controversial. The aim of this study was to assess the relationship between body mass index (BMI), aggressive clinicopathological features of DTC and response to therapy in Saudi population. Methods: We evaluated 209 patients retrospectively who underwent total thyroidectomy at a referral center and diagnosed with DTC. Patients were stratified into 2 groups based on their BMI: non-obese (< 30 kg/m2), and obese (≥ 30 kg/m2). Pathological aggressiveness of DTC as well as clinical outcome were evaluated according to the 2015 American Thyroid Association (ATA) guideline. Data were described as mean ± SD and the categorical data as frequency percent. Mann Whitney test measured the difference in medians of all the metric variables and Chi-square test was applied for the categorical data to measure the intergroup difference between obese and non-obese binary dependent variable. All the inferences were carried out at 95% confidence interval in SPSS 25.0 software. Results: One-hundred twenty (57.4%) of our cohort were obese. Obesity was significantly more common in females (61.7%) than males (29.6%); (p=0.002). There were no differences in histopathological features between the non-obese and obese patients, including tumor size (2.3 ± 1.7 cm vs. 2.5 ± 2.1 cm, respectively, P-value = 0.812), extrathyroidal extension (16.9 % vs. 22.4 %, respectively, P-value=0.336), vascular invasions (25 % vs 18.4 %, respectively, P-value= 0.263) and lymph nodes metastasis (N1a 19.3 % vs 11.6 %, N1b 12.0 % vs. 10.7 % respectively, with P-value = 0.289), were shown between the two groups. In addition, no differences were evident in the ATA risk of recurrence (P-value = 0.843), TNM stage (P-value= 0.797), response to therapy (P-value= 0.252) and survival (P-value= 0.389) across the two groups. Conclusion: No association between BMI and DTC aggressiveness were found in our study population of Saudi patients. In addition, no association were demonstrated between BMI and response to therapy in DTC. These findings suggest that BMI may not be an independent risk factor for aggressiveness in DTC and that other traditional clinicopathological factors should be applied for risk assessment.

Trabecular bone score in women with differentiated thyroid cancer on long-term TSH-suppressive therapy.

Thyrotropin stimulating hormone (TSH) suppression in patients with differentiated thyroid cancer (DTC) aims to decrease the growth and proliferation of thyroid cancer cells. However, the effect of TSH-suppressive therapy on bone microarchitecture remains undefined. Cross-sectional study including 43 women with DTC undergoing TSH-suppressive therapy (sTSH) compared to 20 women also on levothyroxine (LT4) therapy but with TSH in the low-normal range (nTSH) since the thyroid surgery. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA), and trabecular bone score (TBS) was evaluated using the TBS iNsigth software. Fracture risk assessed by FRAX, with and without TBS, was calculated. The relationship between suppressive therapy-related parameters and bone parameters was investigated. The TBS mean values were not significantly different in the sTSH and nTSH groups (1.273 ± 0.12 vs 1.307 ± 0.14, p = 0.7197). In both groups, postmenopausal women had degraded microarchitecture (TBS 1.216 ± 0.11 vs 1.213 ± 0.09, p = 0.9333), while premenopausal women had normal microarchitecture (1.328 ± 0.11 vs 1.401 ± 0.12, p = 0.195). The percentage of all postmenopausal women with degraded TBS was 54.7%, while the percentage of osteoporosis diagnoses was 16.1%. The TBS-adjusted FRAX-probability of fracture was similar in sTSH and nTSH groups. Body mass index (BMI) and menopausal status were the only variables associated with TBS and BMD. Trabecular microarchitecture assessed by TBS was similar between women on long-term suppressive therapy in DTC and those on LT4 replacement therapy aiming at a TSH level within the low-normal reference range. Low TBS values were observed in postmenopausal women of both groups, suggesting that not only suppressed TSH levels but also a low-normal TSH is associated with deteriorated bone microarchitecture in postmenopausal women following total thyroidectomy.

Advancements in the treatment of differentiated thyroid cancer.

Derived from follicular epithelial cells, differentiated thyroid cancer (DTC) accounts for the majority of thyroid malignancies. The threefold increase in DTC incidence over the last three decades has been largely attributed to advancements in detection of papillary thyroid microcarcinomas. Efforts to address the issue of overtreatment have notably included the reclassification of encapsulated follicular variant papillary thyroid cancers (EFVPTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In the last 5 years, the overall management approach for this relatively indolent cancer has become less aggressive. Although surgery and radioiodine ablation remain the mainstay of DTC therapy, the role of active surveillance is being explored. Furthermore, the most recent American Thyroid Association (ATA) guidelines offer flexibility between lobectomy and total thyroidectomy for thyroid nodules between 1 cm and 4 cm in the absence of extrathyroidal extension or nodal disease. As our understanding of the natural history and molecular underpinnings of DTC evolves, so might our approach to managing low-risk patients, obviating the need for invasive intervention. Simultaneously, advances in interventional and systemic therapies have greatly expanded treatment options for high-risk surgical candidates and patients with widespread disease, and continue to be areas of active investigation. Continued research efforts are essential to improve our ability to offer effective individualized therapy to patients at all disease stages and to reduce the incidence of recurrent and progressive disease.

Effects of levothyroxine therapy on bone mineral density and bone turnover markers in premenopausal women with thyroid cancer after thyroidectomy.

We investigated the impact of long-term levothyroxine (LT4) treatment on bone mineral density (BMD) and bone turnover markers (BTMs) in premenopausal women with differentiated thyroid cancer (DTC) after thyroidectomy. Sixty-five premenopausal women who received LT4 therapy at least one year (range, 1.5-9.0 years) after thyroidectomy for DTC and 50 premenopausal women without thyroid diseases were enrolled in this study. We measured the Z-scores of lumbar and hip BMD, serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), intact parathyroid hormone (iPTH), N-terminal propeptide of type 1 N procollagen (P1NP), C terminal telopeptide of type 1 collagen (CTX-1), calcium (Ca), phosphorus (P), vitamin D3, and alkaline phosphatase (ALP) in all participants. In DTC subjects, serum TSH levels were lower, and serum FT4, P1NP, CTX-1, and ALP levels were higher compared with controls. The prevalence of low BMD was higher in DTC subjects than in controls. Multivariate logistic regression analysis showed that serum TSH levels were negatively associated with CTX-1 and ALP. We found a high prevalence of low BMD among premenopausal women who received long-term LT4 therapy for DTC after thyroidectomy. Long-term TSH suppression therapy was a significant risk factor for decreased bone strength, mainly by increasing bone turnover.

Comparison of I-131 Biokinetics after Recombinant Human TSH Stimulation and Thyroid Hormone Withdrawal Measured by External Detector in Patients with Differentiated Thyroid Cancer.

The aim of this study was to compare radioactive iodine (I-131) biokinetics after recombinant human TSH stimulation (rhTSH) and thyroid hormone withdrawal (THW) in patients with differentiated thyroid cancer (DTC). External effective dose rates were measured using external detectors and imaged quantitatively at the time of discharge from the isolation wards. We retrospectively analyzed 32 patients who had been diagnosed with DTC, papillary or follicular, and underwent remnant ablation after either rhTSH stimulation (n=22) or THW (n=10). The uptake of I-131 by remnant thyroid tissue was measured from 20.0 cm, 100.0 cm and 200.0 cm distances using a handheld external detector. The remnant thyroid tissue measured by the whole body images two to five days from administration was 10.7+26.0% (range 0.5 to 60.0%). The values measured at 20 cm were best correlated to the thyroid residual uptake measured by SPECT/CT. The half-lives of I-131washout (T1/2) in rhTSH group measured by external detector were shorter than those of THW group. T1/2 becomes longer when it was measured over longer distances. They were 10.9, 12.3 and 13.1 hours at distances of 20, 100, and 200 cm in rhTSH group, respectively. The TWH group showed 12.8, 14.9 and 17.7 hours, respectively. We conclude that I-131 biokinetics can be measured by external detector after high dose I-131 therapy for DTC. It showed that washout of I-131 was faster after rhTSH stimulation than THW, and slower in patients with distant metastasis than those without metastasis.

Influence of Thyroid-stimulating Hormone Suppression Therapy on Bone Mineral Density in Patients with Differentiated Thyroid Cancer: A Meta-analysis.

BackgroundThe effects of subclinical hyperthyroidism on bone mineral density (BMD) induced by thyroid-stimulating hormone (TSH) suppression therapy in patients with differentiated thyroid cancer (DTC) remains unclear. We conducted a meta-analysis to determine the influence of TSH suppression therapy on BMD.MethodsWe performed a systematic search to identify studies which included BMD measurement of femoral neck, total hip or lumbar spine in patients on TSH suppression therapy for DTC. Main outcome measures were difference of BMD of femoral neck, total hip or lumbar spine measured by dual energy X-ray absorptiometry between patients and controls.ResultsA systematic search yielded a total of 11 published controlled cross-sectional studies (including about 571 patients and 836 controls). TSH suppression therapy was associated with the lower BMD of total hip (weighted mean difference [WMD], −0.023; 95% confidence interval [CI], −0.047 to 0.000; P=0.050) and spine (WMD, −0.041; 95% CI, −0.057 to −0.026; P<0.001) in postmenopausal women with DTC, while it was not associated with that in premenopausal women and men with DTC.ConclusionsAlthough the included studies were limited by small numbers, results suggested possible association between chronic TSH suppression therapy and the lower BMD of spine and total hip in postmenopausal women (but not in premenopausal women and men) with DTC. A large, well-designed study with long-term follow-up would provide further insight into the influence of TSH suppression therapy and loss of BMD.

Predictive factors determining incomplete response to radioiodine therapy in patients with differentiated thyroid cancer.

Although differentiated thyroid cancer (DTC) has relatively favorable course, factors predicting the course of the disease are intensively searched. The aim of the study was to identify the clinical factors determining incomplete response to radioiodine therapy in patients with DTC. We retrospectively analyzed 385 consecutive patients with DTC treated and followed-up at a single tertiary reference center. We investigated clinical factors detectable during first hospitalization 3-6 months following total thyroidectomy due to DTC, which may serve as prognostic factors determining response to DTC therapy in a long-term follow-up. Stimulated thyroglobulin (sTg) was the only parameter significantly correlated with the cumulative radioiodine activity (r=0.247, P<0.001). The need for repeated radioiodine administration (≥3 doses) was best predictable on the basis of sTg concentration assessed at the moment of qualification to radioiodine therapy (P=0.003). Predictive value of the sTg for incomplete response to radioiodine has been confirmed with the ROC curve analysis and the best proposed cut-off value was 8.17 ng/mL (sensitivity 55%, specificity 77%, positive predictive value 42.1%, negative predictive value 84.7%); sTg over 8.17 ng/mL increases the risk of incomplete response to therapy 2.5-folds (P=0.002). sTg, assessed at the moment of qualification to radioiodine therapy, as the most important factor determining incomplete response to radioiodine therapy in patients with DTC, should be particularly taken into consideration in predicting the future course of the disease as well as treatment and follow-up planning. Radical thyroidectomy may help to increase the effectiveness of treatment.

I-131 Radiation-Induced Myelosuppression in Differentiated Thyroid Cancer Therapy.

Radioactive iodine (RAI) treatment of differentiated thyroid cancer has been used in clinical practice for almost 60 years and is generally accepted to be a safe and efficacious treatment. Severe toxicity in the form of radiation pneumonitis, sometimes progressing to fibrosis, and bone marrow suppression are reported but remain rare. We present a case of severe myelosuppression requiring hospitalization and transfusion support in an otherwise well, young female patient who had received 175 mCi I-131 for low-volume micronodular lung disease one month prior, with a cumulative lifetime administered activity of 575 mCi. The most important risk factors for myelosuppression following RAI are the activity received, the amount of functioning thyroid tissue present, and the lifetime cumulative activity received.

Clinical therapy and management of differentiated thyroid cancer in pregnant women

Differentiated thyroid cancer (DTC) is frequently found in mid-aged and young women. DTC has been the second common malignancy diagnosed during pregnancy. The clinical therapy of DTC has involvement of both mother’s health and fetal safety and thus is usually difficult. Currently, there are still controversies in the therapy of DTC in pregnant women. Herein we summarize the advance in the surgical therapy, radioactive iodine therapy and thyroid hormone replacement therapy in pregnancy and after delivery and explore more effective strategies which are beneficial for the mother and fetus, which willprovide more evidence for the selection of strategies for the clinical management of DTC in pregnant women.

Second or none: Many patients treated for refractory differentiated thyroid cancer with small molecular kinase inhibitors do not receive a second line of therapy.

e17589 Background: Describe the treatment patterns of patients initiated on NCCN-recommended small molecular kinase inhibitors (SMKIs) for radioiodine-refractory differentiated thyroid cancer (DTC) approved in the United States. Methods: A large national US claims database was used to identify adult patients diagnosed with thyroid cancer (≥2 non-DX medical claims, ≥ 30 days apart) from 1/1/2006 - 6/30/2016 (study period) with claims for SMKIs from 1/1/2010 - 5/31/2016. Continuous enrollment required participation in a commercial or Medicare Advantage health plan ≥3 months before and ≥1 month following index date (date of first pharmacy claim for SMKI). Line of therapy (LOT) periods were defined by receipt and timing of SMKIs. Patient follow up was earliest disenrollment, death or end of the study period. Patient characteristics and SMKI treatment patterns were described. Results: A total of 217 DTC patients were identified; 63% commercially insured and 37% Medicare Advantage. Almost half were male (48%); mean age was 61.2 years (standard deviation SD 12.5 years) and mean follow-up period was 499 days (SD 414 days). In the study period, 35% (n = 77) of patients had ≥2 LOTs and 18% (n = 39) had ≥3 LOTs. Mean treatment duration was 5.4 months (SD 6.7 mos) for LOT1, 4.9 months (SD 3.8 mos) for LOT2, and 4.2 months (SD 4.9 mo) for LOT3. During the full study period, the most used regimens were Sorafenib for both LOT1 (37%) and LOT2 (25%), pazopanib (18%) and sunitinib (18%) in LOT3. Also, in the study period, 33 patients had sorafenib in LOT1 of which 16 were treated with sorafenib again (48%) in LOT2. Post FDA approval in 2015, Lenvatinib became the predominant first-line regimen (47%, n = 29) during study period. Across all first line therapies, for those patients with ≥12 months of follow-up, 53% (n = 60) initiated LOT2. Conclusions: Sorafenib was the most common first line of therapy for DTC, with Lenvatinib adoption increasing as first-line therapy since the drug’s approval in 2015. Depending on the period evaluated, almost half to 2/3 of patients are not receiving a second line of treatment, efficacious and patient appropriate therapy is of importance in treating this rare cancer.

Current controversies in the initial post-surgical radioactive iodine therapy for thyroid cancer: a narrative review.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the fifth most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post-thyroidectomy patient has included radioactive iodine (RAI) ablation and/or therapy. Before 2000, a typical RAI post-operative dose recommendation was 100 mCi for remnant ablation, 150 mCi for locoregional nodal disease, and 175-200 mCi for distant metastases. Recent recommendations have been made to decrease the dose in order to limit the perceived adverse effects of RAI including salivary gland dysfunction and inducing secondary primary malignancies. A significant controversy has thus arisen regarding the use of RAI, particularly in the management of the low-risk DTC patient. This debate includes the definition of the low-risk patient, RAI dose selection, and whether or not RAI is needed in all patients. To allow the reader to form an opinion regarding post-operative RAI therapy in DTC, a literature review of the risks and benefits is presented.

An update on clinical trials of targeted therapies in thyroid cancer

Several new targeted therapies with multikinase inhibitors targeting vascular endothelial growth factor (VEGF), rearranged during transfection and v-raf murine sarcoma viral oncogene homolog B1 pathways have been tested in clinical trials for radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in the past 10 years. Results of the first phase III trial of VEGF-targeted therapy (sorafenib) in DTC were presented in June 2013, and two phase III trials with VEGF and rearranged during transfection-targeted therapies (vandetanib and cabozantinib) in MTC have led to approval by US Food and Drug Administration in the past 2 years. Whereas such therapies increase median progression-free survival compared to placebo, there is no therapy proven to improve overall survival yet. Significant potential adverse event risks associated with such therapies need to be recognized. Dissemination of knowledge about targeted therapies is critical for various medical specialists as patient care for thyroid cancers is best delivered in a multidisciplinary setting. Successful development of targeted systemic therapies in DTC and MTC in the past 5 years is incredibly exciting in the field and patients with advanced DTC/MTC now have new standard-of-care therapy options.