Radioiodine-refractory Differentiated Thyroid Cancer Research Articles

Baseline Tumour Size as a Prognostic Factor for Radioiodine-refractory Differentiated Thyroid Cancer Treated With Lenvatinib.

Lenvatinib is standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC), although the optimal timing for starting treatment is still controversial. The aim of this study was to evaluate the prognostic impact of baseline tumour size (BTS) in patients with RR-DTC treated with lenvatinib. Fifty-one RR-DTC patients who had at least one measurable lesion and treated with lenvatinib were retrospectively analysed. BTS was defined as the sum of the longest dimensions of all measurable target lesions. Median progression-free survival (PFS) and overall survival (OS) in the larger BTS (≥42 mm) group were shorter than those in the smaller (<42 mm) group. This result was more significant in patients with fast-growing tumours. BTS was an independent prognostic factor for both PFS and OS. Starting lenvatinib at BTS <42 mm should be recommended to achieve good treatment outcomes in patients with RR-DTC.

Impact of age on survival in radioiodine refractory differentiated thyroid cancer patients

The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age. This single-center, retrospective study enrolled 155 patients diagnosed with RAIR-DTC. The primary end point was overall survival (OS) according to different cutoff (45, 55, 65, 75 years). Secondary endpoints were progression free survival (PFS) and prognostic factors in patients under and over 65 years. Median OS after RAIR diagnosis was 8.2 years (95% IC: 5.3-9.6). There was no difference according to age with a 65 (P = 0.47) and 55 years old cutoff (P = 0.28). Median OS improved significantly before 45 years old (P = 0.0043). After 75 years old, median OS significantly decreased (P = 0.0008). Median PFS was 2.1 years (95% CI: 0.8-3) in patients < 65 years old, and 1 year in patients ≥ 65 years old (95% CI: 0.8-1.55) with no statistical difference (P = 0.22). There was no impact of age on PFS with any cutoff. In both groups, progressive disease despite 131I treatment reduced OS. In patients < 65 years old, an interval of less than 3 years between the initial diagnosis and the diagnosis of RAIR metastatic disease was predictive of poor survival. In patients > 65 years old, the presence of a mediastinum metastasis was a significant factor for mortality (HR: 4.55, 95% CI: 2.27-9.09). In RAIR-DTC patients, a cut-off age of 65 years old was not a significant predictive factor of survival. Forty-five and 75-years-old cutoff were predictive for OS but not PFS.

Do Molecular Profiles of Primary Versus Metastatic Radioiodine Refractory Differentiated Thyroid Cancer Differ?

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25–82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer

BackgroundLung metastases may worsen overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study). Patients and methods392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to open-label lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated. ResultsLenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions ≥1.0 cm (n = 199), ≥1.5 cm (n = 150), ≥2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57–1.01; P = 0.0549). Median OS for lung metastases of ≥1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47–0.85; P = 0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of ≥1.0 cm, ≥1.5 cm, ≥2.0 cm and <2.0 cm; median OS was shorter in the ≥2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1–49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of ≥1.0 cm after adjustment for baseline characteristics. ConclusionsLenvatinib treatment resulted in longer OS in patients with lung metastases of ≥1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of ≥1.0 cm. Source study registrationClinicalTrials.Gov Identifier: NCT01321554.

Downregulation of miR-146b-3p Inhibits Proliferation and Migration and Modulates the Expression and Location of Sodium/Iodide Symporter in Dedifferentiated Thyroid Cancer by Potentially Targeting MUC20.

The dedifferentiation of differentiated thyroid cancer (DTC) is a challenging problem for radioactive iodine (131I) treatment, also known as radioiodine refractory differentiated thyroid cancer (RAIR-DTC). The purpose of this study was to further explore the mechanism of the redifferentiation of dedifferentiated thyroid cancer. Ineffective and effective groups of 131I therapy were analyzed and compared in both our clinical and TCGA samples. Whole-exome sequencing, mutation analysis, transcriptome analysis, and in vitro functional experiments were conducted. FLG, FRG1, MUC6, MUC20, and PRUNE2 were overlapping mutation genes between our clinical cases, and the TCGA cases only appeared in the ineffective group. The expression of miR-146b-3p target MUC20 was explored. The expression levels of miR-146b-3p and MUC20 were significantly increased, and the inhibition of miR-146b-3p expression significantly inhibited proliferation and migration, promoted apoptosis, regulated the expression and location of thyroid differentiation-related genes, and sodium/iodide symporter (NIS) in dedifferentiated thyroid cancer cells (WRO). Thus, miR-146b-3p potentially targets MUC20 participation in the formation of DTC dedifferentiation, resulting in resistance to 131I and the loss of the iodine uptake ability of DTC cancer foci, promoting refractory differentiated thyroid cancer. miR-146b-3p may be a potentially therapeutic target for the reapplication of 131I therapy in dedifferentiated thyroid cancer patients.

Modern approaches to the treatment of radioiodine-refractory differentiated thyroid cancer

Radioiodine therapy is the main post-operation method of treatment of advanced differentiated thyroid cancer, but the loss of ability of iodine uptake causes the poor prognosis. The follow-up of patients with radioiodine-refractory differentiated thyroid cancer (RRDTC) is a serious problem. In review the definition, genesis, diagnostics and treatment of RRDTC were revealed. Taking into account the ineffectiveness of traditional methods of redifferentiation therapy, the perspectives of administration of targeted therapies with tyrosine kinase inhibitors were showed. Key words: radioiodine-refractory differentiated thyroid cancer, radioiodine therapy, targeted therapies with tyrosine kinase inhibitors.

Prognostic significance of 8 weeks’ relative dose intensity of lenvatinib in treatment of radioiodine-refractory differentiated thyroid cancer patients

Lenvatinib is a standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, because of the high incidence of adverse events resulting from this treatment, it is not easy to maintain the dose intensity of lenvatinib, especially in Japanese patients. Although the prognostic impact of lenvatinib dose interruption has been reported, the target dose intensity of lenvatinib to optimize survival benefits remains unknown. We therefore propose a target dose intensity of lenvatinib during the first 8 weeks of treatment. We retrospectively analyzed 42 RR-DTC patients who were treated with lenvatinib for more than 8 weeks. We performed receiver operating characteristic curve analysis to determine the cut-off value of 8 weeks' relative dose intensity (8w-RDI) to predict treatment response, and identified that the optimal cut-off value of 8w-RDI was 60% (sensitivity: 81.8%; specificity: 80.6%). Median progression-free survival (PFS) (not reached [NR] vs. 11.0 months; hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.11-0.72; p < 0.01) and overall survival (NR vs. 27.6 months; HR 0.44; 95% CI 0.11-0.91; p = 0.03) were longer in the higher 8w-RDI (≥60%) patients than in the lower 8w-RDI (<60%) patients. Multivariate analysis revealed that 8w-RDI at ≥60% was an independent prognostic factor for PFS (HR 0.29; 95% CI 0.09-0.96; p = 0.04). Targeting for ≥60% of the relative dose intensity during the first 8 weeks of lenvatinib treatment can be sufficient to achieve significant tumor shrinkage and prolong PFS in RR-DTC patients.

Lenvatinib: A narrative drug review

The discovery and clinical efficacy of imatinib in chronic myeloid leukemia opened a new and interesting avenue of oral small-molecule tyrosine kinase inhibitors. Thereafter, several such molecules with efficacy across multiple tumor types have been discovered. One of the oral multi-kinase inhibitors is lenvatinib, which started its journey in 2008 when it showed efficacy on stem cells in the laboratory setting and was first approved by the United States Food and Drug Administration in August 2015 for the management of radioiodine-refractory differentiated thyroid cancer. Since then, it has been approved for hepatocellular, endometrial, and renal cell carcinomas, and many more trials are underway for lenvatinib in multiple solid tumors, either alone or in combination with immunotherapy. In addition to the robust data on the efficacy of this drug, it is known for its tolerability with different dosing schedules in different tumor types, a feature unique to this drug. Therefore, an in-depth understanding of its mechanism of action, pharmacokinetics, pharmacodynamics, dosage in different tumor types, expected side effects, and predictors of response will go a long way in its safe and appropriate use in the clinics. In this review, we aim to summarize and collate these data in a reader-friendly manner, thus making it a ready reckoner for lenvatinib. We searched the PubMed database for full-text articles on lenvatinib published in the last 10 years using the search terms “lenvatinib,” “hepatocellular carcinoma,” renal cell carcinoma,” “thyroid carcinoma,” “and “endometrial carcinoma”. A total of 1053 studies were identified, of which 60 were included in this review.

Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria.

Background Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. Methods Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39–91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). Results PFS after 24 months was 71% (95% CI: 56–87), and overall survival (OS) was 74% (95% CI: 60–88), respectively. OS was significantly shorter (p=0.048) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39–86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66–98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). Conclusion Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

426P A multicenter, randomized, double-blind, phase II study of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) to evaluate the safety and efficacy of a daily oral starting dose of 18 mg vs 24 mg

426P A multicenter, randomized, double-blind, phase II study of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) to evaluate the safety and efficacy of a daily oral starting dose of 18 mg vs 24 mg

421P A multicenter, randomized, double-blind, placebo (PBO)-controlled, phase III trial of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in China

421P A multicenter, randomized, double-blind, placebo (PBO)-controlled, phase III trial of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in China

High Prevalence and Conservative Management of Acute Cholecystitis during Lenvatinib for Advanced Thyroid Cancer

Introduction: Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor currently used for advanced, radioiodine refractory differentiated thyroid cancer (RAI-R DTC). Among adverse events (AEs), nausea, vomiting, and decreased appetite have been frequently described. We aimed to evaluate the prevalence, the clinical presentation, and the effectiveness of conservative treatment of gallbladder disorders in a consecutive series of patient treated with LEN. Methods: Patients with RAI-R DTC experiencing clinical symptoms suggestive for gallbladder disorders during LEN treatment were evaluated with laboratory investigations and contrast-enhanced abdominal computed tomography (CT) and ultrasound scan (US). Results: After a median time of 2 months from the start of treatment, 5/13 patients (38.4%) complained of gastrointestinal symptoms, with increased biliary enzymes levels, especially γGT, and CT/US suggestive of acute cholecystitis (AC). The onset of symptoms and the peak of γGT levels frequently corresponded to the highest reduction in body weight during the first months of treatment. All patients were treated with supportive care and, when appropriate, with ursodeoxycholic acid; in 4 patients, LEN dose reduction or short interruption was needed, too. Conclusions: In patients with RAI-R DTC treated with LEN, a high prevalence of AC in the first months of treatment was documented. Mainly due to the low specificity of symptoms such as anorexia, nausea, and vomiting, this AE is likely to be frequently misdiagnosed. The onset of the disease was associated to the weight loss observed during the first months of treatment and contributes to further decrease in body weight. Therefore, particularly during the first months of treatment, or at any time of huge reduction of body weight, monitoring of γGT and US is crucial for prompt diagnosis and treatment. Conservative medical treatment and LEN dosage titration, together with dietary and rehabilitative supports, can limit or avoid the need for drug withdrawal and cholecystectomy.

Lenvatinib as first-line treatment for advanced thyroid cancer: long progression-free survival.

Lenvatinib (LEN) has been approved for the treatment of patients with progressive radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). Real-life studies reported a lower progression-free survival (PFS) than the registration study, likely due to the more advanced stage of tumors, the more frequent pretreatment with other TKIs, the limited follow-up, and the worse clinical condition of the patients included. We evaluated the clinical data of our cohort of 13 consecutive patients, all receiving LEN as a first-line TKI treatment, and followed-up in a single tertiary Center. All patients had an ECOG of 0-1 and regional or distant metastases were documented in 61.5% and 77% of patients, respectively. Median PFS was 22 months (95% CI 14-35) with partial response in 69% and stable disease in 31% of patients. All patients experienced at least one adverse event (AE), the most frequent being fatigue, anorexia, diarrhea, and hypertension. The daily dose was reduced in 70% of patients and only one patient (7.7%) discontinued the drug for AEs. In this series of RAI-R DTC patients, with the unique features to have an ECOG 0 or 1 and to be naive for TKI treatments, PFS was the longest among all real-life published so far, with the highest rate of patients with partial response and one of the lowest drug discontinuation rate for AEs. The correct timing of treatment start, the tailoring of the dose, and a proper management of the AEs may have a significant impact on the treatment response to LEN.

1924P Diagnostic demographics of radioiodine-refractory differentiated thyroid cancer (RR-DTC) and usage patterns of local and systemic therapies (ERUDIT study)

Advanced differentiated thyroid carcinoma (aDTC), herein defined as locally unresectable or metastatic disease, frequently develops into RR-DTC, one of the most common late-stage endocrine tumours. However, available data about its evolution is limited. ERUDIT is a multicentre, observational, retrospective study of patients diagnosed with aDTC in Spain and Portugal. The study describes its natural history from the initial diagnosis until the advanced stages of disease. This communication is focused on the RR-DTC subpopulation, its diagnosis, treatment patterns, and specialties involved in its management. Clinical records from patients ≥18 y-o diagnosed with aDTC (including poorly differentiated DTC) with first evidence of advanced disease documented between January 2007 and August 2017 were retrospectively reviewed until death or lost to follow-up. 213 patients were identified in 23 centres. Median age at initial diagnosis was 63 y-o, 59% were females. aDTC presented de novo in 54% of the cases. In all, 77.5% were initially diagnosed or developed into RR-DTC along study follow-up. Median (Q1-Q3) time to RR-DTC from first radioiodine dose was 27.6 (9.5-50.6) months. Computed (CT) and fluorodeoxygucose positron emission tomography (FDG PET-CT) were the most used methods to follow refractory disease (41% and 27%, respectively). Management was multimodal, with surgery (15%), watchful waiting (48%), locoregional (35%), and systemic therapies (ST) (37%) being used. Median (Q1-Q3) time from RR-DTC diagnosis to start of ST was 8.9 (1.4-34.7) months, while median overall survival (95%CI) reached 4.7 (3.4-8.0) years in this subpopulation. Endocrinology (59%) and Oncology (33%) were the leading medical specialties responsible for patient monitoring, while two thirds of the patients were evaluated by multidisciplinary committees. Most of aDTC tumours either present or become RR-DTC in around 2.3 years and are treated multidisciplinarily. Survival expectancy of this group nears 5 years, confirming an unfavourable evolution of most aDTC at their late treatment stages.

1923P Assessment of the efficacy and safety of lenvatinib for the treatment of radioiodine-refractory differentiated thyroid cancer in real-life practice in Russia

1923P Assessment of the efficacy and safety of lenvatinib for the treatment of radioiodine-refractory differentiated thyroid cancer in real-life practice in Russia

Unusual metastases from differentiated thyroid cancers: A multicenter study in Korea.

Although infrequent, distant metastasis from differentiated thyroid cancer is the main cause of mortality in patients and mostly involves the lung, bone, and brain. Distant metastases to other sites in differentiated thyroid cancer patients are rare, thus, the clinical course of unusual metastases has not been adequately researched. In the present study, the clinico-pathological findings and treatment outcomes of unusual metastases in differentiated thyroid cancer patients in Korea were evaluated. We retrospectively reviewed the medical records of differentiated thyroid cancer patients with unusual metastases in four Korean tertiary hospitals (Chonnam National University Hwasun Hospital, Asan Medical Center, Busan National University Hospital, Severance Hospital). Unusual metastases were diagnosed using (1) cytology or histology and/or (2) imaging studies including fluorodeoxyglucose F 18 positron emission tomography/computed tomography and/or iodine 131 whole body scans with simultaneously elevated serum levels of thyroglobulin. The pathological findings of primary thyroid cancer, diagnostic method for unusual metastases, and treatment responses of unusual metastases were examined. In all, 25 unusual metastatic foci of 19 patients were analyzed; 13 patients (68.4%) had papillary thyroid carcinoma including 4 follicular variant papillary thyroid carcinomas. The median time interval between the first diagnosis of primary thyroid cancer and unusual metastases diagnosis was 110 months (11.0-138.0 months). Only 4 patients (21.1%) had synchronous unusual metastases and 6 patients (31.6%) were symptomatic. Unusual metastases included 19 metastases to solid organs (6 to kidney, 5 to liver, 4 to pancreas, 3 to adrenal gland, and 1 to ovary) and 6 to the skin and muscles. Unusual metastases were pathologically proven in 10 patients (52.6%) and 11 of 16 patients (68.8%) who received iodine 131 whole body scans had radioiodine-refractory differentiated thyroid cancer. Among 5 patients treated with tyrosine kinase inhibitors, 4 treated with lenvatinib showed stable disease or a partial response at the first treatment response. Six patients (31.6%) died due to disease progression during the median 20.0-month follow-up period (11.0-55.0 months). Unusual metastases from differentiated thyroid cancer are thought to be underestimated due to disease rarity and their metachronous nature with other distant metastases. The most of unusual metastases in differentiated thyroid cancer patients are existed with usual distant metastasis and clinical outcomes of those could not be significantly different from the prognosis of usual distant metastasis.

The value of contrast-enhanced 18F-FDG PET/CT for indication of loco-regional surgery in radioiodine-refractory differentiated thyroid cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Lenvatinib plus pembrolizumab combination therapy in patients with radioiodine-refractory (RAIR), progressive differentiated thyroid cancer (DTC): Results of a multicenter phase II international thyroid oncology group trial.

6512 Background: Lenvatinib is an approved therapy for patients with RAIR DTC. While the overall response rate (ORR) is high, few patients achieve a complete response (CR) and most patients eventually have progressive disease (PD). Combination lenvatinib and pembrolizumab is being explored in many different cancers, and this combination has been approved for advanced endometrial carcinoma. Methods: Patients with RAIR DTC with Response Evaluation Criteria in Solid Tumor (RECIST v1.1) measurable PD (&lt;14 months (mo) prior to registration) were enrolled in this single-arm multicenter phase II study. Patients were excluded if they had received previous VEGFR-directed multikinase therapy. The lenvatinib starting dose was 20 mg/day orally and pembrolizumab was 200mg IV every 3 weeks. The primary endpoint was CR. ORR, progression-free survival (PFS) and safety graded by Common Terminology Criteria for Adverse Events v4.0 were secondary endpoints. Results: Thirty patients were enrolled. The median age was 62.5 years, and 53% of the patients were women. Seventy percent of patients had grade 3 adverse events (AEs) and 10 percent had grade 4 AEs. There were no treatment-related deaths. The most common &gt; grade 3 AEs were hypertension (47%), weight loss (13%), maculopapular rash (13%), leukopenia (7%), diarrhea (7%) and oral mucositis (7%). Twenty-one patients (70%) required lenvatinib dose reduction. Of 29 evaluable patients, 18 (62%) had a partial response (PR) and 10 (35%) had stable disease (SD). The clinical benefit rate (ORR +SD) was 97%. Median time to tumor nadir was 7.4 mo (1.6-17.8 mo). Median PFS was not yet reached. The PFS at 12 months was 74%. Median time on therapy was 9.9 mo (3.2-18.9 mo). Fourteen patients are continuing therapy (7.6-18.9 mo). Six of these patients (43%) have not yet reached tumor size nadir. Three patients (10%) had &gt; 80% target tumor shrinkage. Conclusions: Lenvatinib plus pembrolizumab is reasonably tolerated in patients with RAIR DTC. To date, there have been no documented complete responses. Combination lenvatinib plus pembrolizumab therapy has a high ORR in patients with RAIR DTC. Continuation of this study will help determine the depth and length of the responses. Clinical trial information: NCT02973997 .

MON-LB76 Impact of Age on Survival and Prognostic Factors in Radioiodine Refractory Differentiated Thyroid Cancer Patients

BACKGROUNDAge has been identified as a major prognostic factor in differentiated thyroid cancer (DTC). Prognostic factors of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) are poorly described. The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age.PATIENTS AND METHODThis single centre, retrospective study enrolled 155 patients diagnosed with a RAIR-DTC between 1991 and 2017. The primary end point was overall survival (OS). Secondary endpoints were progression free survival (PFS) and prognostic factors.RESULTSMedian OS was 8.2 years (95% IC: 5.3-9.6). There was no difference according to age (P = 0.47) with median OS at 8.3 years in patients < 65 (95% IC: 4.9-10), and 7.5 years in patients > 65 (IC: 4,9-11,3). PFS after RAIR-diagnosis was 2.1 years (95% IC: 0.8-3) in patients < 65, and 1 year in patients > 65 (95% IC: 0.34-0.68). In both groups, progressive disease despite 131I reduced OS, in comparison with other RAIR criteria. In patients < 65, an interval between the initial diagnosis of DTC and the diagnosis of RAIR metastatic disease more than 3 years was protective from poor OS (HR: 2.12; 95% CI: 1.05-4.27). In patients > 65, presence of a mediastinum metastasis at RAIR-diagnosis was a significant factor for decreased OS (HR: 0.22; 95% CI: 0.11-0.44).No difference was found between groups regarding therapeutic management. One third of patients received tyrosine kinase inhibitors in both groups (< 65 years: 20 patients (28%), ≥ 65 years: 28 (33%), P = 0.49). They were also similar regarding the number of lines received or the median duration of treatment (< 65 years: 19.5 months (2-59), ≥ 65 years: 19 months (1-64), p= 0.35). At least one line of TKI was transitorily or definitively withdrawn due to toxicity in 40% of patients (< 65 years: 8/20 patients (40%), ≥ 65 years: 13/28 (46%), p= 0,037).CONCLUSIONIn RAIR-DTC patients, age was not predictive of the outcome. In our study, older patients seem to have benefited from intensive therapeutic management. Continual progress made in the management of RAIR-DTC, especially with the implementation of systemic therapies should probably make reconsider the natural history and conventional prognostic factors of RAIR-DTC.

Sorafenib use in patients with radioiodine-refractory differentiated thyroid cancer - A five-year experience at the ISSSTE National Medical Center 20 de Noviembre in Mexico City

Sorafenib use in patients with radioiodine-refractory differentiated thyroid cancer - A five-year experience at the ISSSTE National Medical Center 20 de Noviembre in Mexico City