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Thyroid cancer is one of the most common malignant tumors. After standardized surgery, selective
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ABSTRACT Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. Subjects and methods: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.
Subject(s)
Humans , Thyroid Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Prognosis , Positron Emission Tomography Computed Tomography , Iodine RadioisotopesABSTRACT
We report a case of a 47-year-old female known with metastatic papillary thyroid cancer. Her treatment history included total thyroidectomy and 3 previous radio ablations with a cumulative dose of 950 mCi of ¹³¹I. On follow-up, her thyroglobulin levels had demonstrated a rising trend (from 3789.0 to 4240.0 ug/L) despite a ¹²³I whole-body scan demonstrating a reduction in tracer avid lesions. She was suspected of having radio-resistant disease. The patient underwent both ¹⁸F-FDG and ⁶⁸Ga-PSMA PET/CT imaging with both scans demonstrating congruent lesions however with far greater intensity on the ⁶⁸Ga-PSMA study.
Subject(s)
Female , Humans , Middle Aged , Follow-Up Studies , Iodine , Positron Emission Tomography Computed Tomography , Thyroglobulin , Thyroid Gland , Thyroid Neoplasms , ThyroidectomyABSTRACT
ABSTRACT Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluordeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multikinase inhibitors (MKIs) being the most investigated drugs. Two of these compounds, sorafenib and lenvatinib, have shown significant objective response rates and have significantly improved the progression-free survival in the two largest published prospective trials on MKI use. However, no overall survival benefit has been achieved yet. This is probably related to the crossover that occurs in most patients who progress on placebo treatment to the open treatment of these studies. In consequence, the challenge is to correctly identify which patients will benefit from these treatments. It is also crucial to understand the appropriate timing to initiate MKI treatment and when to stop it. The purpose of this article is to define RAI refractoriness, to summarize which therapies are available for this condition, and to review how to select patients who are suitable for them.
Subject(s)
Humans , Thyroid Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Iodine Radioisotopes/therapeutic use , Antineoplastic Agents/therapeutic use , Radiation Tolerance , Thyroid Neoplasms/mortality , Thyroid Neoplasms/radiotherapy , Treatment Failure , Retreatment , Disease ManagementABSTRACT
Objective:To evaluate the biochemical and structural changes of apatinib in patients with progressive radioactive iodine-re-fractory differentiated thyroid cancer (RAIR-DTC). Methods:The participants (n=10) were followed up since March 2016. Treatment ef-fect was evaluated in using both biochemical [thyroglobulin (Tg) and thyroglobulin antibody (Tg-Ab)] and structural responses (target lesions, TL). Adverse events were also recorded over time. Results:The median follow-up was 7.9 months. The Tg level declined rapid-ly within 6 weeks after apatinib treatment, and the average decline ranged from 60%to 90%, indicating the immediate biochemical re-sponse of apatinib in progressive RAIR-DTC. The Tg level tended to stabilize thereafter. However, the Tg level rebounded by 4%–135%when withdrawal was performed for 3–14 days. The number of TLs decreased rapidly within 8 weeks, and the average decreased ranged from 40%to 60%, indicating the presence of rapid structural responses. Thereafter, the number of TLs continued to stabilize. TLs, in contrast to Tg, were not significantly affected by drug withdrawal. The rate of change in Tg (Tgvn) was positively correlated with the rate of change in TL (TLvn) [TLvn=0.17×Tgvn+0.50 (r=0.56, P<0.05)]. The apatinib dose was adjusted due to adverse events, which could be relieved after 3 to 14 days of withdrawal. Apatinib can effectively control the disease even at a reduced dose of 250 mg/d. Conclusion:Apatinib treatment showed a fast and sustainable biochemical and structural responses. Tg could be regarded as an objec-tive indicator. Tgvn is positively correlated with TLvn, and the response of Tg is more sensitive than that of TLs.
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Background and purpose:Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a big challenge in the management of thyroid cancer. Sorafenib and lenvatinib are the 2 tyrosine kinase inhibitors (TKIs) recently approved by FDA, which could not be affordable for most of the Chinese patients. This pilot study aimed to evaluate the short term effcacy and safety of apatinib, a Chinese domestic TKI targeted vascular endothelial growth factor receptor (VEGFR), in advanced RAIR-DTC.Methods:Ten patients who were identiifed as progressive RAIR-DTC were enrolled in this study. Patients received oral apatinib 750 mg once daily. Both thyroglobulin (Tg) and/or Tg antibody (TgAb) levels were monitored every 2 weeks after the treatment. Computed tomography (CT) was per-formed every 4 weeks after apatinib treatment to evaluate the response according to response evaluation criteria in solid tumor version 1.1 (RECIST 1.1). Within 8 weeks after apatinib treatment, therapeutic response was evaluated in terms of Tg, a sensitive biochemical tumor marker for DTC, and RECIST 1.1 assessment. Meanwhile, the adverse events (AE) were monitored during the therapy.Results:The Tg levels declined after the ifrst 2 weeks of apatinib treatment, and a mean decline rate of 68% could be observed in 8 patients with Tg available for evaluation after 8 weeks, which repre-sented a biochemical partial response. Eighteen target lesions (TL) of 10 patients were evaluated and followed up. The diameter of TL began to decrease after 4 weeks, and a mean decline of 40% could be observed after 8 weeks’ apatinib treatment. A total of 9 patients (9/10) achieved partial response according to RECIST 1.1 criteria and 1 patient with stable disease, with 90% objective response rate and 100% disease control rate. The most common AE beyond grade 3 included hand-foot-skin reactions, hypertension and hypocalcemia, which accounted for 50%, 30% and 20% of the cases, respectively. No severe AE related to apatinib was observed during the treatment.Conclusion:A safe and rapid response and high partial response rate in terms of biochemistry, RECIST 1.1 could be observed in RAIR-DTC patients within 8 weeks of apatinib treatment.
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Most patients with thyroid cancer (of follicular cell origin) are successfully managed with a combination of surgery, radioactive iodine (131I-RAI), and suppression of thyroid-stimulating hormone with thyroid hormone replacement, obtaining survival rates approaching 90% at 20 years. Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is favorable, recurrence occurs in up to 30% patients. In addition, many patients with recurrent or metastatic disease, as well as those with less differentiated tumors, will have a much poorer prognosis and lose their ability to concentrate functional iodine and are therefore not targeted by 131I-RAI therapy. There are many treatment options but no definitive treatment for radioiodine refractory thyroid cancer. This paper will discuss the roles of surgical treatment for patients with radioiodine refractory thyroid cancer.
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Humans , Iodine , Methods , Prognosis , Recurrence , Survival Rate , Thyroid Gland , Thyroid Neoplasms , ThyrotropinABSTRACT
Unlike most thyroid cancers which have an excellent prognosis with standard treatments such as surgery and additional radioactive iodine therapy followed by long term TSH suppression, 15-20% of differentiated thyroid cancers are unresponsive, showing locally aggressive behavior or distant metastasis. It has been reported that the ability of iodine uptake among residual follicular cells is usually impaired in such unresponsive cases. As the general incidence of thyroid cancer increases, the number of this radioactive iodine refractory disease is also increasing. This becomes clinically challenging because iodine-based diagnostic and therapeutic approaches are not applicable anymore. Moreover, other conventional modalities including radiotherapy or cytotoxic chemotherapy is neither effective in this subset of thyroid cancer. So many researches are currently under way to find effective molecular targeted therapies, which will play a role in the treatment of these unresectable and advanced cases. This review discusses the recent research progress regarding the iodine avidity of follicular cells in thyroid cancer, and outcomes of clinical studies using targeted agents.