Reversing “Flip-Flop” Phenomenon of 131I and Glucose Avidity in RET-Fusion Positive Radioiodine-Refractory Thyroid Cancer Lesions After Treatment of Pralsetinib

Chan, Hung-Pin; Chen, I-Feng; Tsai, Fu-Ren; Kao, Chun-Hao; Shen, Daniel Hueng-Yuan

doi:10.1097/rlu.0000000000004475

Cited by 7 publications

(3 citation statements)

References 9 publications

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“…For instance, Groussin and colleagues ( 120 ) described one case of successful redifferentiation therapy with Larotrectinib in a patient with metastatic PTC harboring an EML4-NTRK3 gene fusion. Similarly, restoration of radioiodine uptake in patients with RET -fusion positive RR-DTC has been reported following treatment with selective RET-inhibitors pralsetinib ( 121 ) and selpercatinib ( 122 ).…”

Section: Redifferentiation Therapymentioning

confidence: 73%

Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance

et al. 2023

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The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in many centers. However, none of the currently available treatments are curative, and most patients will ultimately show progression. Current research efforts are therefore focused on identifying resistance mechanisms to tyrosine kinase inhibitors and ways to overcome them. Various novel treatment strategies are under investigation, including immunotherapy, redifferentiation therapy, and second-generation kinase inhibitors. In this review, we will discuss currently available drugs for advanced RR-DTCs, potential mechanisms of drug resistance and future therapeutic avenues.

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Section: Redifferentiation Therapymentioning

confidence: 73%

Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance

et al. 2023

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“…Selpercatinib treatment was resumed post-surgically and the patient remained locoregionally disease-free with stable metastatic disease (after an initial partial response) 21 months after starting therapy. The possibility to reinduce radioiodine uptake in DTC cases previously demonstrated to have lost such ability has been also explored by some authors ( 93 – 96 ). These results should be confirmed in a prospective clinical trial even if the low number of cases represents a big limit to the enrolment.…”

Section: Future Directionsmentioning

confidence: 99%

Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe

et al. 2023

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The incidence of thyroid cancer is increasing worldwide with the disease burden in Europe second only to that in Asia. In the last several decades, molecular pathways central to the pathogenesis of thyroid cancer have revealed a spectrum of targetable kinases/kinase receptors and oncogenic drivers characteristic of each histologic subtype, such as differentiated thyroid cancer, including papillary, follicular, and medullary thyroid cancer. Oncogenic alterations identified include B-Raf proto-oncogene (BRAF) fusions and mutations, neurotrophic tyrosine receptor kinase (NTRK) gene fusions, and rearranged during transfection (RET) receptor tyrosine kinase fusion and mutations. Multikinase inhibitors (MKIs) targeting RET in addition to multiple other kinases, such as sorafenib, lenvatinib and cabozantinib, have shown favourable activity in advanced radioiodine-refractory differentiated thyroid cancer or RET-altered medullary thyroid cancer; however, the clinical utility of MKI RET inhibition is limited by off-target toxicity resulting in high rates of dose reduction and drug discontinuation. Newer and selective RET inhibitors, selpercatinib and pralsetinib, have demonstrated potent efficacy and favourable toxicity profiles in clinical trials in the treatment of RET-driven advanced thyroid cancer and are now a therapeutic option in some clinical settings. Importantly, the optimal benefits of available specific targeted treatments for advanced RET-driven thyroid cancer require genetic testing. Prior to the initiation of systemic therapy, and in treatment-naïve patients, RET inhibitors may be offered as first-line therapy if a RET alteration is found, supported by a multidisciplinary team approach.

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“…[ 18 F]FDG PET/CT can also be used for follow-up and to predict the success of redifferentiation therapies with BRAF, MEK, or RET inhibitors [29,30]. Weber et al used MAPK inhibitors in a prospective study to enhance radioiodine uptake in RAI-R DTC (ERRITI trial) [30].…”

Section: [ 18 F]fdgmentioning

confidence: 99%

Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer

Petranović Ovčariček,

Campenni,

de Keizer

et al. 2023

Cancers

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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.

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Reversing “Flip-Flop” Phenomenon of 131I and Glucose Avidity in RET-Fusion Positive Radioiodine-Refractory Thyroid Cancer Lesions After Treatment of Pralsetinib

Cited by 7 publications

References 9 publications

Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance

Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance

Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe

Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer

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