Preoperative neoadjuvant targeted therapy for inoperable differentiated thyroid cancer: a case report

Abstract Background: The majority of differentiated thyroid cancer (DTC) has good prognosis after a careful standardized therapy according to the current guidelines. However, approximately 13% to 15% of DTC shows surprisingly aggressive behavior and invades the surrounding structures, and then a few is very difficult to remove. In that specific context, preoperative neoadjuvant targeted therapy may improve the clinical stage and create an opportunity for operation.Case presentation: We reported a case of 64-year-old woman with locally advanced papillary thyroid cancer (PTC) who presented with dysphagia due to seemingly unresectable tumor, which severely invaded the left esophagus at the junction of neck and thorax, difficult to undergo a safe and complete removal. With an approvement of institution ethics committee, this patient was treated with neoadjuvant therapy (apatinib 500mg orally qd).Six weeks later, the tumor dramatically shrunk from 56*37mm to 29*26mm with well-controlled mild hypertension. After 10 days interval of apatinib withdrawal, complete tumor excision was accomplished without esophagus fistula. Postoperative inhibition and radioiodine 131I ablation were performed. At one-year follow-up evaluation, no tumor recurrence or metastasis was observed.Conclusion: Preoperative short-termed targeted treatment for locally advanced inoperable DTC may become a promising neoadjuvant therapy, which can reduce the tumor size and decrease stage, thus being convenient for complete and safe removal.

Download Full-text

Cabozantinib, Nivolumab, and Ipilimumab in Treating Patients With Radioactive Iodine-Refractory Differentiated Thyroid Cancer That Progressed After VEGFR-Targeted Therapy

Case Medical Research ◽

10.31525/ct1-nct03914300 ◽

2019 ◽

Author(s):

Keyword(s):

Thyroid Cancer ◽

Targeted Therapy ◽

Differentiated Thyroid Cancer ◽

Radioactive Iodine

Download Full-text

Neoadjuvant Therapy in Differentiated Thyroid Cancer

International Journal of Surgical Oncology ◽

10.1155/2016/3743420 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Rajan P. Dang ◽

Daniel McFarland ◽

Valerie H. Le ◽

Nadia Camille ◽

Brett A. Miles ◽

...

Keyword(s):

Thyroid Cancer ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Differentiated Thyroid Cancer ◽

Potential Role ◽

Kinase Inhibitors ◽

Tracheal Resection ◽

Complete Surgical Resection ◽

Select Trial ◽

Short Time

Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy.Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan.Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data.Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC.

Download Full-text

The role of Hashimoto thyroiditis in predicting radioiodine ablation efficacy and prognosis of low to intermediate risk differentiated thyroid cancer

Annals of Nuclear Medicine ◽

10.1007/s12149-021-01644-1 ◽

2021 ◽

Author(s):

Domenico Albano ◽

Francesco Dondi ◽

Valentina Zilioli ◽

Maria Beatrice Panarotto ◽

Alessandro Galani ◽

...

Keyword(s):

Thyroid Cancer ◽

Treatment Response ◽

Differentiated Thyroid Cancer ◽

Hashimoto Thyroiditis ◽

Prognostic Impact ◽

Intermediate Risk ◽

Excellent Response ◽

Radioiodine Ablation ◽

One Year

Abstract Objective The baseline treatment of differentiated thyroid cancer (DTC) consists of thyroidectomy followed by postoperative risk-adapted radioiodine therapy (RAIT) when indicated. The choice of most appropriate RAI activities to administer with the aim to reach an efficient remnant ablation and reduce the risk of recurrence is yet an open issue and the detection of basal factors that may predict treatment response seems fundamental. The aim of this study was to investigate the potential role of Hashimoto thyroiditis (HT) in predicting 1-year and 5-year treatment response after RAIT and prognosis. Methods We retrospectively included 314 consecutive patients (174 low-risk and 140 intermediate-risk) who received thyroidectomy plus RAIT. One-year and 5-year disease status was evaluated according to 2015 ATA categories response based upon biochemical and structural findings. Results HT was reported histopathologically in 120 patients (38%). DTC patients with concomitant HT received a higher number of RAITs and cumulative RAI activities. Initial RAIT reached an excellent response in 63% after one year and 84% after 5 years. The rate of excellent response one year and 5-year after first RAIT was significantly lower in HT groups, compared to not HT (p < 0.001). Instead, HT did not have a prognostic role considering PFS and OS; while stimulate thyroglobulin (sTg) at ablation was significantly related to survival. Conclusions HT may affect the efficacy of RAIT in low to intermediate risk DTC, particularly reducing the successful rate of excellent response after RAIT. Instead, HT did not have a prognostic impact such as stimulated sTg.

Download Full-text

Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

Journal of Clinical Oncology ◽

10.1200/jco.2017.73.0226 ◽

2017 ◽

Vol 35 (29) ◽

pp. 3315-3321 ◽

Cited By ~ 39

Author(s):

Maria E. Cabanillas ◽

Jonas A. de Souza ◽

Susan Geyer ◽

Lori J. Wirth ◽

Michael E. Menefee ◽

...

Keyword(s):

Thyroid Cancer ◽

Targeted Therapy ◽

Phase Ii ◽

Differentiated Thyroid Cancer ◽

Kinase Inhibitor ◽

Objective Response ◽

Evaluation Criteria ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

Download Full-text

Adjuvant External Beam Radiotherapy in Locally Advanced Differentiated Thyroid Cancer

JAMA Otolaryngology–Head & Neck Surgery ◽

10.1001/jamaoto.2017.2077 ◽

2017 ◽

Vol 143 (12) ◽

pp. 1244 ◽

Cited By ~ 11

Author(s):

Samantha Tam ◽

Moran Amit ◽

Mongkol Boonsripitayanon ◽

Maria E. Cabanillas ◽

Naifa L. Busaidy ◽

...

Keyword(s):

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

External Beam Radiotherapy ◽

Locally Advanced ◽

External Beam

Download Full-text

Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Results from the phase 3 COSMIC-311 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6001 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6001-6001

Author(s):

Marcia S. Brose ◽

Bruce Robinson ◽

Steven I. Sherman ◽

Barbara Jarzab ◽

Chia-Chi Lin ◽

...

Keyword(s):

Thyroid Cancer ◽

Targeted Therapy ◽

Disease Progression ◽

Differentiated Thyroid Cancer ◽

Statistical Significance ◽

Phase 1 ◽

Objective Response ◽

Standard Of Care ◽

Clinical Activity ◽

Phase 3

6001 Background: Cabozantinib (C), an inhibitor of VEGFR2, MET, AXL, and RET, showed clinical activity in patients (pts) with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC) in phase 1/2 studies (Cabanillas 2017; Brose 2018). This phase 3 study (NCT03690388) evaluated the efficacy and safety of C vs placebo (P) in pts with RAI-refractory DTC who had progressed during/after prior VEGFR-targeted therapy for whom there is no standard of care. Methods: In this double-blind, phase 3 trial, pts were randomized 2:1 to receive C (60 mg QD) or P, stratified by prior lenvatinib treatment (L; yes, no) and age (≤65, > 65 yr). Pts with RAI-refractory DTC must have received L or sorafenib for DTC and progressed during or following treatment with ≤ 2 prior VEGFR inhibitors. Pts randomized to P could cross over to open-label C upon disease progression per blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (ORR) in the first 100 randomized pts and progression-free survival (PFS) in all randomized pts. PFS and ORR were assessed by BIRC per RECIST v1.1. The study was designed to detect an ORR for C vs P (2-sided α = 0.01) and a hazard ratio (HR) for PFS of 0.61 (90% power, 2-sided α = 0.04). A prespecified interim PFS analysis was planned for the ITT population at the time of the primary ORR analysis. Results: As of 19 Aug 2020,125 vs 62 pts had been randomized to the C and P arms, respectively; median age was 66 yr, 55% were female and 63% received prior L. Median (m) follow-up was 6.2 months (mo). At the planned interim analysis, the trial met the primary endpoint of PFS with C demonstrating significant improvement over P (HR 0.22, 96% CI 0.13–0.36; p < 0.0001). mPFS was not reached for C vs 1.9 mo for P; PFS benefit was observed in all prespecified subgroups including prior L (yes, HR 0.26; no, HR 0.11) and age (≤65 yr, HR 0.16; > 65 yr, HR 0.31). ORR was 15% for C vs 0% for P (p = 0.0281) but did not meet the prespecified criteria for statistical significance (p < 0.01). A favorable OS trend was observed for C vs P (HR 0.54, 95% CI 0.27–1.11). Treatment-emergent adverse events (AEs) of any grade with higher occurrences in the C vs P arm included diarrhea (51% vs 3%), hand-foot skin reaction (46% vs 0%), hypertension (28% vs 5%), fatigue (27% vs 8%), and nausea (24% vs 2%); grade 3/4 AEs were experienced by 57% of pts with C vs 26% with P. Dose reductions due to any grade AEs occurred in 57% of pts with C vs 5% with P. Treatment discontinuations due to AEs not related to disease progression occurred in 5% of pts with C vs 0% with P. No treatment-related deaths occurred in either arm. Conclusions: C showed a clinically and statistically significant improvement in PFS over P in pts with RAI-refractory DTC after prior VEGFR-targeted therapy with no unexpected toxicities. C may represent a new standard of care in pts with previously treated DTC. Clinical trial information: NCT03690388.

Download Full-text