Radioiodine-refractory Differentiated Thyroid Cancer Research Articles

Safety and efficacy of nintedanib as second-line therapy for patients with differentiated or medullary thyroid cancer progressing after first-line therapy. A randomized phase II study of the EORTC Endocrine Task Force (protocol 1209-EnTF).

Nintedanib is a triple-angiokinase inhibitor with potential activity in patients with advanced thyroid cancers, as radioiodine refractory differentiated thyroid cancer (RAIR DTC) and medullary thyroid cancer (MTC). EORTC-1209 (NCT01788982) was a double-blind randomized (2:1 ratio) placebo-controlled phase II, multi-cohort study exploring the efficacy and safety of nintedanib in patients with progressive, locally advanced, and/or metastatic RAIR DTC and MTC. The primary endpoint was progression-free survival (PFS) in the per-protocol (PP) population for both cohorts. Secondary endpoints included response rate, duration of response, overall survival (OS), and safety. RAIR DTC cohort: Seventy out of the 75 planned patients with RAIR DTC (median age, 66 years; 39 women) who had progressed after one (76%) or two lines (24%) of previous systemic therapy were randomized to receive either nintedanib (N = 45) or placebo (N = 25). Of these, 69 patients started treatment and 56 met all inclusion criteria (PP). At data cutoff, the median duration of follow-up was 26.3 months in the nintedanib arm and 19.8 months in the placebo arm. In the PP population, the median PFS was 3.7 months [80% confidence interval (CI), 1.9-6.5] in the nintedanib arm and 2.9 months (80% CI, 2.0-5.6) in the placebo arm (HR = 0.65; 80% CI, 0.42-0.99; one-sided log-rank test P = 0.0947). No objective response was observed. The median OS was 29.6 months [80% CI, 15.2-not reached (NR)] in the nintedanib arm and not reached in the placebo arm. Grade 3-4 adverse events of any attribution occurred in 50% of patients receiving nintedanib and in 36% of patients receiving placebo. MTC cohort: Thirty-one out of the 67 planned patients with MTC (median age, 57 years; eight women) who had progressed after one (68%) or two (32%) lines of previous systemic therapy were randomized to receive either nintedanib (N = 22) or placebo (N = 9). Of these, 20 patients (15 in the nintedanib arm and five in the placebo arm) started treatment and met all inclusion criteria (PP). The median PFS was 7.0 months (80% CI, 1.9-8.7) in the nintedanib arm and 3.9 months (80% CI, 3.0-5.5) in the placebo arm (HR = 0.49; 95% CI, 0.16-1.53). No objective response was reported. The median OS was 16.4 months (80% CI, 12.1-24.9) in the nintedanib arm and 12.3 months (80% CI, 7.1-NR) in the placebo arm. Grade 3-4 adverse events of any attribution during the blinded period occurred in 59.1% of patients receiving nintedanib and in 33.3% of patients receiving placebo. This study did not suggest a clinically significant improvement of PFS with nintedanib over placebo in patients with pretreated RAIR DTC and MTC.

125I seed implantation for lymph node metastasis from radioactive iodine-refractory differentiated thyroid carcinoma: a study on short-term efficacy and dosimetry.

To investigate the feasibility and evaluate the safety and effectiveness of Computed Tomography (CT) guided125I radioactive particle implantation for treating lymph node metastases in radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). To verify the accuracy of the computerized three-dimensional treatment planning system (TPS) in treating lymph node metastasis using125I particle implantation at the dosimetric level. A retrospective analysis was conducted on 42 patients with RAIR-DTC and lymph node metastases who were admitted to the General Hospital of the Northern Theater Command between December 2016 and January 2019. During this analysis, physicians utilized preoperative CT images to design an intraoperative plan using TPS. The dosimetric parameters of the postoperative plan were then compared to the preoperative plan. Additionally, this study examined the changes in tumor size and tumor-related marker Thyroglobulin (Tg) values in patients at 2, 6, and 12 months after the operation. The number of125I radioactive particles implanted in 42 patients was 226, with an average of 14.5 (range 2.0-30.0) particles implanted per lesion. The local remission rates were 97.62% (41/42), 88.10% (37/42), and 85.71% (36/42) at 2, 6, and 12 months postoperatively, respectively. The volume of the lesions was (4.44 ± 1.57) cm3, (4.20 ± 1.70) cm3, and (4.23 ± 1.77) cm3at 2, 6, and 12 months after treatment, respectively, which significantly decreased from the preoperative baseline level of (6.87 ± 1.67) cm3(t-values: 9.466, 9.923, 7.566, all P<0.05). The Tg levels were 15.95 (5.45, 73.93) μg/L, 8.90 (2.20, 39.21) μg/L, and 6.00 (1.93, 14.18) μg/L at 2, 6, and 12 months after treatment, respectively, which were significantly lower than the preoperative baseline levels of 53.50 (20.94, 222.92) μg/L (Z values: -5.258, -5.009, -4.987, all P < 0.001). Postoperatively, Delivered to 90% of the GTV(D90) was slightly lower than the prescribed dose in 95.23% (40/42) of patients, but the difference was not statistically significant [(12,378.8 ± 3,182.0), (12,497.8 ± 1,686.4) cGy; t=0.251, P>0.05], and postoperative dose parameters delivered to 100% of the gross tumor volume (GTV)(D100) (6,881.5 ± 1,381.8) cGy, the volume percentages of GTV receiving 150% of the prescribed dose(V150) (58.5 ± 18.40)%) were lower than the preoperative plan D100 (8,085.8 ± 2,330.0) cGy, V150 (66.5 ± 17.70)%; t-value=8.913 and 3.032, both P<0.05; the remaining indicators were not significantly different from the preoperative plan (the differences in the number of implanted particles, Planning Target Volume(PTV), the volume percentages of GTV receiving 100% of the prescribed dose(V100), Homogeneity Index(HI)were not statistically significant (t/Z = -0.593, -1.604, 1.493, -0.663, all P>0.05). Referring to the TPS preoperative plan, the125I particle implantation therapy for RAIR-DTC lymph node metastasis can achieve the expected dose distribution, ensuring precise short-term local tumor control efficacy.

Efficacy and safety of second-line treatment with surufatinib for anlotinib-resistant radioiodine-refractory differentiated thyroid cancer: An exploratory multicenter study.

e15127 Background: Radioiodine-refractory differentiated thyroid cancer (RR-DTC) resistant to first-line targeted therapy typically exhibits rapidly progressive nature, lacking standard treatment options. This study aimed to assess the efficacy and safety of surufatinib, targeting vascular endothelial growth factor receptor 1/2/3, fibroblast growth factor receptor 1, and colony-stimulating factor-1 receptor, in RR-DTC patients who had failed anlotinib treatment. Methods: This multicenter study enrolled patients aged ≥ 18 years with at least one measurable RR-DTC lesion (RECIST 1.1), who had previously received anlotinib treatment and experienced disease progression. Primary endpoint was progression-free survival (PFS); secondary endpoints were disease control rate and safety. Results: As of December 25, 2023, 9 patients were enrolled. Median age, 56 (range, 29-69) years; Male, 88.9%; ECOG PS 0, 88.9%; papillary carcinoma/follicular carcinoma, 77.8%/22.2%. Lung (77.8%) and bone (33.3%) were the most frequently involved organs. The duration of anlotinib treatment ≤ 12 months was found in 44.4% patients. All the 9 patients underwent at least one efficacy evaluation with a median PFS of 6.3 months and disease control rate of 88.9%. Subsequent analysis revealed that median PFS extended to 9.20 months in patients younger than 56 years, compared to 5.95 months in older individuals. Patients with over 12 months of prior anlotinib treatment exhibited mPFS of 9.20 months, versus 6.25 months in those with shorter prior treatment durations. Common treatment-emergent adverse events observed were hypertension (44.4%), proteinuria (22.2%), decreased platelets (22.2%), fatigue (11.1%), and hemoptysis (11.1%). Grade 3 adverse events included proteinuria (11.1%), fatigue (11.1%), and hemoptysis (11.1%). Conclusions: In patients with anlotinib-resistant RR-DTC, second-line surufatinib treatment yielded promising efficacy and tolerable toxicity, warranting randomized controlled studies on RR-DTC refractory to first-line targeted therapy. Clinical trial information: ChiCTR2100052020 .

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2024

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2024

Ten years' real-life experience on the use of multikinase inhibitors in patients with advanced differentiated thyroid cancer.

To evaluate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) associated with tyrosine kinase inhibitors (TKIs) in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Additionally, to compare: (i) ORR and PFS among patients treated with lenvatinib and sorafenib; (ii) ORR and PFS among patients receiving lenvatinib as first-line vs. second-line and; (iii) adverse effects (AEs) observed in patients treated with these medications. Retrospective analysis of RR-DTC adult patients treated with TKIs at the Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires (March 2011-November 2023). Among 43 patients included in the study, 32 received sorafenib (30 as first-line and 2 as second-line), while 29 received lenvatinib (12 as first-line and 17 as second-line). The median PFS and OS for the entire cohort were 32.7 and 39.0 months, respectively. Lenvatinib demonstrated a significantly higher ORR compared to sorafenib (37.9% vs. 9.4%, p = 0.008). However, both drugs exhibited similar median PFS (23.2 vs. 16.0 months, p = 0.419). No significant difference was observed in ORR and PFS between patients receiving first-line vs. second-line lenvatinib. Sorafenib-treated patients experienced higher rates of hand-foot skin syndrome (69% vs. 41%, p = 0.032) and alopecia (25% vs. 3%, p = 0.018), whereas lenvatinib-treated patients had higher rates of proteinuria (31% vs. 0%, p < 0.001) and grade 3 hypertension (31% vs. 9%, p = 0.034). TKIs demonstrated efficacy and tolerability comparable to real-world data in RR-DTC. PFS was not statistically different between sorafenib and lenvatinib. Our study will help guide physicians in making informed decisions regarding treatment sequencing with TKIs in these patients.

Donafenib as neoadjuvant therapy in locally advanced thyroid cancer: protocol for the DONATHYCA phase II prospective single-arm trial in China

IntroductionThe invasion of important structures in locally advanced thyroid cancer (LATC) hinders radical resection, increases the risk of recurrence and even prevents surgery. Creating the opportunity for radical operation in...

Efficacy and safety of tyrosine kinase inhibitors for advanced metastatic thyroid cancer: A systematic review and network meta-analysis of randomized controlled trials.

Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains unknown which regimen is the best choice for these patients. We conducted a systematic review and network meta-analysis to compare the survival benefits and efficacy of the available first-line regimens. We conducted an active search for phase II, III, or IV randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to compare the effects of at least 2 drugs in the systemic treatment of advanced or metastatic thyroid cancer up to May 2023. The network meta-analysis model was adjusted using Bayesian Network model. Twelve trials with 2535 patients were included in our meta-analysis. The overall survival (OS), progression-free survival (PFS), and serious adverse events (SAEs) were taken as reference indicators. We also performed subgroup analyses of OS and PFS in medullary thyroid cancer (MTC) and radioiodine-refractory differentiated thyroid cancer (RR-DTC) to explore the variations of TKIs in different groups. As a result, apatinib had the best effect on overall survival (OS) (hazards ratio [HR] = 0.42, 95% confidence interval [CI] = 0.18-0.98), lenvatinib 18 mg/d has the best effect on progression-free survival (PFS) (HR = 0.13, 95% CI = 0.064-0.27), and cabozantinib 60 mg/d has the best safety profile. Our network meta-analysis showed that we believe that cabozantinib has the potential to become a widely used drug in clinical practice.

“Watch and wait” approach in the treatment of advanced radioiodine refractory differentiated thyroid cancer: a study of barriers and drivers of use

Introduction. The multikinase inhibitors have demonstrated high clinical efficacy in treatment of the radioiodine refractory differentiated thyroid cancer. At the same time, the inclusion criteria in the studies has reflected a minimum set of characteristics important for beginning of use of these drugs and an approach that takes into account the tumor progression rate (the volume doubling time) in the absence of clinical manifestations of the disease that have made it possible to individualize the start of therapy. Aim. To describe and evaluate the barriers and drivers of use the “watch and wait” approach by Russian oncologists in treatment of the radioiodine refractory thyroid cancer. Materials and methods. We conducted 35 structured interviews with oncologists observing patients after radioiodine therapy in order to evaluate the “watch and wait” approach. unfortunately, data on use and prevalence of this approach in Russia are limited. The present study involved the use of deductive content analysis as well as analysis of implementation model of clinical guidelines and included investigation of issue of implementation of the “watch and wait” approach to current practice of therapy for radioiodine refractory differentiated thyroid cancer. One of the main tasks was to determine the influence of external factors on the treatment of this category of patients. Conclusion. Barriers and drivers of using “watch and wait” approach in the treatment of differentiated radioiodine refractory thyroid cancer are identified at several levels. for wide use of this approach, it is necessary to involve oncologists taking into account their attitude regarding changes in routine practices, patient expectations and to obtain additional data regarding its long-term effectiveness.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1&amp;#945; After Treatment: A Cell Regulation Study

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1&amp;#945; After Treatment: A Cell Regulation Study

Population pharmacokinetic-pharmacodynamic modeling of serum biomarkers as predictors of tumor dynamics following lenvatinib treatment in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC).

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor (FGF) receptors 1-4, platelet-derived growth factor receptor-α (PDGFRα), KIT, and RET that have been implicated in pathogenic angiogenesis, tumor growth, and cancer. The primary objective of this work was to evaluate, by establishing quantitative relationships, whether lenvatinib exposure and longitudinal serum biomarker data (VEGF, Ang-2, Tie-2, and FGF-23) are predictors for change in longitudinal tumor size which was assessed based on data from 558 patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) receiving either lenvatinib or placebo treatment. Lenvatinib PK was best described by a 3-compartment model with simultaneous first- and zero-order absorption and linear elimination from the central compartment with significant covariates (body weight, albumin <30 g/dL, ALP>ULN, RR-DTC, RCC, HCC subjects, and concomitant CYP3A inhibitors). Except for body weight, none of the covariates have any clinically meaningful effect on exposure to lenvatinib. Longitudinal biomarker measurements over time were reasonably well defined by a PK/PD model with common EC50, Emax, and a slope for disease progression for all biomarkers. Longitudinal tumor measurements over time were reasonably well defined by a tumor growth inhibition Emax model, which in addition to lenvatinib exposure, included model-predicted relative changes from baseline over time for Tie-2 and Ang-2 as having significant association with tumor response. The developed PK/PD models pave the way for dose optimization and potential prediction of clinical response.

Survival predictors of radioiodine-refractory differentiated thyroid cancer treated with lenvatinib in the real-life.

Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete. To identify pre- and post- treatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib. Multicenter, retrospective, cohort study. Three Italian thyroid cancer referral centers. 55 RR-DTC treated with lenvatinib. Progression-free survival (PFS) and overall survival (OS). Lenvatinib was the first-line kinase-inhibitor in 96.4% of subjects. Median follow-up was 48 months. Median PFS and OS were 26 (95% CI 19.06-32.93) and 70 months (95% CI 36-111.99), respectively. Pre-treatment setting: Eastern Cooperative Oncology Group (ECOG) performance status was independently related to PFS (p < 0.001; HR 18.82; 95% CI 3.65-97.08: score 0-1 as reference) and OS (p = 0.001; HR 6.20; 95% CI 2.11-18.20; score 0-1 as reference); radioactive iodine (RAI)-avidity was independently related to PFS (p = 0.047; HR 3.74; 95% CI 1.01-13.76; avid disease as reference). Patients with good ECOG status (0-1) and RAI-avid disease obtained objective response in 100% of cases and achieved a median PFS of 45 months without any death upon a median follow-up of 81 months. Post-treatment setting: best radiological response independently predicted PFS (p = 0.001; HR 4.6; 95% CI 1.89-11.18; partial/complete response as reference) and OS (p = 0.013; HR 2.94; 95% CI 1.25-6.89; partial/complete response as reference). RR-DTC with good performance status and RAI-avid disease obtain the highest clinical benefit from lenvatinib. After treatment initiation, objective response was the only independent survival predictor.

Tyrosine kinase inhibitors for radioiodine refractory differentiated thyroid cancer: A systematic review and meta-analysis.

The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs)in radioiodine refractory differentiated thyroid cancer (RAIR-DTC).However, the available evidence cannot determine the optimal choice of TKI in RAIR-DTC. This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT)of RAIR-DTCpatients treated with the TKI system. Outcomes, including progression-free survival (PFS),overall survival (OS),and adverse events (AEs)were reported. Seven studies involving 1310 patients with RAIR-DTCwas conducted to compare the PFS and OS of various TKImonotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR]0.19, 95% credible interval [CrI] 0.14-0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18-0.97) and anlotinib (HR0.36, 95% CrI 0.18-0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR-DTC,although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR-DTCpatients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment. The results of this meta-analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine-refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR-DTC.This study is beneficial for formulating patients' treatment plans and guides clinicians' decision-making.

Cabozantinib Increases Progression–free Survival in Radioiodine–Refractory Differentiated Thyroid Cancer across Tumor Histologies and after Previous Anti–VEGF Therapy

Cabozantinib Increases Progression–free Survival in Radioiodine–Refractory Differentiated Thyroid Cancer across Tumor Histologies and after Previous Anti–VEGF Therapy

Real-world treatment patterns and clinical outcomes in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) treated with first line lenvatinib monotherapy in the United States

PurposeLenvatinib was approved for the treatment of patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) in the United States (US) in 2015. The main objective of the current study was to assess real-world clinical effectiveness in RAI-R DTC patients treated with first line lenvatinib monotherapy in the US.MethodsA retrospective chart review was conducted in RAI-R DTC patients who initiated lenvatinib monotherapy as first line treatment between February 2015 and September 2020. Anonymized data were abstracted by prescribing physicians from individual patient’s electronic health records. Clinical outcomes included provider-reported real-world best overall response (rwBOR), real-world progression-free survival (rwPFS), and overall survival (OS). Time-to-event endpoints were assessed using Kaplan–Meier methods.ResultsOur study included 308 RAI-R DTC patients treated with first line lenvatinib. At lenvatinib initiation, patients’ median age was 60 years, 51.6% were female, and 26.0% of patients had an ECOG performance score of ≥2. Over the follow-up period, 32.5% of patients discontinued first line lenvatinib permanently, with others remaining on treatment. The median duration of lenvatinib therapy was 17.5 months overall. Provider-reported rwBOR (complete or partial response) to lenvatinib was 72.4%. Median rwPFS was 49.0 months. Estimated rwPFS rates at 24 and 48 months were 68.5% and 55.0%, respectively. Estimated OS rates at 24 and 72 months were 78.4% and 57.0%, respectively; median OS was not reached.ConclusionThe current study reinforces the clinical effectiveness of first line lenvatinib as standard of care in patients with RAI-R DTC in real-world clinical practice in the US.

604P Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who progressed after prior VEGFR-targeted therapy: Outcomes from COSMIC-311 by BRAF status

604P Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who progressed after prior VEGFR-targeted therapy: Outcomes from COSMIC-311 by BRAF status

Planned drug holidays during treatment with lenvatinib for radioiodine-refractory differentiated thyroid cancer: a retrospective study.

In the phase 3 SELECT study, lenvatinib significantly improved prognostic outcomes vs. placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, toxicity of lenvatinib is sometimes considerable and requires frequent dose interruptions and modifications. Recently, planned drug holidays have been proposed as a means of avoiding severe adverse events (AEs). We retrospectively reviewed medical records to compare the efficacy and safety of lenvatinib in RR-DTC patients who underwent planned drug holidays (planned holiday group) vs. those who received conventional daily oral administration (daily group). The subjects were 25 patients in the planned holiday group and 21 in the daily group. Median age was 73 years (range 43-84) and 62 years (range 42-75), and histologic subtype of papillary/follicular was 21/4 cases and 15/6 cases, respectively. Time to treatment failure (TTF) and overall survival (OS) were significantly longer in the planned holiday group than the daily group (not reached [NR] vs. 14.9 months, hazard ratio [HR] 0.25, 95% confidence interval [Cl] 0.11-0.58, p<0.001; NR vs. 26.6 months, HR 0.20, 95% CI 0.073-0.58, p=0.001, respectively). Median progression-free survival (PFS) was NR in the planned holiday group vs. 15.1 months in the daily group (HR 0.31, 95% CI 0.14-0.68, p=0.002). Duration of the period with lenvatinib dose ≥10 mg was significantly longer in the planned holiday group (NR vs. 6.5 months, HR 0.22, 95% CI 0.10-0.49, p<0.001), and the frequency of drug interruption due to intolerable AEs was lower (68.0% vs. 95.2%, p=0.027). Planned drug holidays for lenvatinib demonstrated significantly longer PFS, TTF, and OS than daily oral administration, and less intolerable toxicity leading to further unplanned treatment interruption. These benefits were apparently associated with a more extended period of lenvatinib administration at ≥10 mg. These findings might contribute to a favorable patient prognosis and safer toxicity profile.

Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [18F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC.

The Efficacy and Safety of Surufatinib Combined with Anti PD-1 Antibody Toripalimab in Neoadjuvant Treatment of Locally Advanced Differentiated Thyroid Cancer: A Phase II Study.

Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting. In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250mg of surufatinib (orally daily) with 240mg of toripalimab (intravenous, every 3weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc. RESULTS: Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2. Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.

Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice.

Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers. With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

Management of radioiodine refractory differentiated thyroid cancer: the Latin American perspective.

Radioiodine (RAI) refractory differentiated thyroid cancer is an uncommon and challenging situation that requires a multidisciplinary approach to therapeutic strategies. The definition of RAI-refractoriness is usually a clear situation in specialized centers. However, the right moment for initiation of multikinase inhibitors (MKI), the time and availability for genomic testing, and the possibility of prescribing MKI and selective kinase inhibitors differ worldwide.Latin America (LA) refers to the territories of the world that stretch across two regions: North America (including Central America and the Caribbean) and South America, containing 8.5% of the world's population. In this manuscript, we critically review the current standard approach recommended for patients with RAI refractory differentiated thyroid cancer, emphasizing the challenges faced in LA. To achieve this objective, the Latin American Thyroid Society (LATS) convened a panel of experts from Brazil, Argentina, Chile, and Colombia. Access to MKI compounds continues to be a challenge in all LA countries. This is true not only for MKI but also for the new selective tyrosine kinase inhibitor, which will also require genomic testing, that is not widely available. Thus, as precision medicine advances, significant disparities will be made more evident, and despite efforts to improve coverage and reimbursement, molecular-based precision medicine remains inaccessible to most of the LA population. Efforts should be undertaken to alleviate the discrepancies between the current state-of-the-art care for RAI-refractory differentiated thyroid cancer and the present situation in Latin America.