Differentiated thyroid cancer (DTC) accountsfor more than 90% of thyroid cancers andhas a typically favorable prognosis (10-year survival rate above 85%). During the last decades,the diagnosis of this tumor has made huge strideswith the widespread use of neck ultrasonography, fine needle aspiration biopsy and genetictesting.1-3 Indeed, DTC is the most frequent endocrine cancer and represents the most rapidlyincreasing human cancer worldwide.Thyroidectomy is the mainstay of treatmentfor this disease. Postoperative radioactive iodine(RAI) therapy represents the “magic bullet” for atargeted treatment of DTC. RAI is used to ablateresidual thyroid tissue, eliminate suspected micrometastases or known advanced disease. However, about 60-70% of patients with metastaticdisease are or will become refractory to RAI. Inpatients with RAI-refractory DTC (RR-DTC)the 10-year survival rate drops to 10-20%.4, 5Although the management and follow-up of patients with DTC is quite well-standardized,6 theoccurrence of RAI resistance represents a complex challenge.7In patients with RR-DTC and single lesion orfew metastatic lesions within the same organ,locoregional therapies (surgery, external-beamradiation therapy, radiofrequency ablation, andethanol ablation or embolization) are suggested.7, 8In patients with progressive or symptomaticplurimetastatic disease, medical therapy withmulti-kinase inhibitors (MKIs) has been recentlyadopted. Sorafenib is a protein kinase inhibitorwith activity against vascular endothelial growthfactor receptor (VEGFR), platelet derivedgrowth factor receptor (PDGFR), rearrangedduring transfection (RET) and BRAF. Lenvatinibis a MKI targeting VEGFRs, fibroblast growthfactor receptor (FGFR), PDFGR, stem cell factor receptor (KIT), and RET. Both sorafenib andlenvatinib prolonged progression-free survivalcompared with placebo in randomized phase 3trials enrolling patients with RR-DTC. Indeed,sorafenib and lenvatinib are approved and usedin daily clinical practice in several countries forpatients with RR-DTC. Unfortunately, the toxicity of these compounds could have a detrimentaleffect on the quality of life of patients. Althoughrandomized controlled trials comparing sorafenibwith lenvatinib are not available in patients withRR-DTC, their efficacy and side effect profilesappear comparable.
Radioiodine-refractory thyroid cancer: a complex challenge
BARREA L
2021-01-01
Abstract
Differentiated thyroid cancer (DTC) accountsfor more than 90% of thyroid cancers andhas a typically favorable prognosis (10-year survival rate above 85%). During the last decades,the diagnosis of this tumor has made huge strideswith the widespread use of neck ultrasonography, fine needle aspiration biopsy and genetictesting.1-3 Indeed, DTC is the most frequent endocrine cancer and represents the most rapidlyincreasing human cancer worldwide.Thyroidectomy is the mainstay of treatmentfor this disease. Postoperative radioactive iodine(RAI) therapy represents the “magic bullet” for atargeted treatment of DTC. RAI is used to ablateresidual thyroid tissue, eliminate suspected micrometastases or known advanced disease. However, about 60-70% of patients with metastaticdisease are or will become refractory to RAI. Inpatients with RAI-refractory DTC (RR-DTC)the 10-year survival rate drops to 10-20%.4, 5Although the management and follow-up of patients with DTC is quite well-standardized,6 theoccurrence of RAI resistance represents a complex challenge.7In patients with RR-DTC and single lesion orfew metastatic lesions within the same organ,locoregional therapies (surgery, external-beamradiation therapy, radiofrequency ablation, andethanol ablation or embolization) are suggested.7, 8In patients with progressive or symptomaticplurimetastatic disease, medical therapy withmulti-kinase inhibitors (MKIs) has been recentlyadopted. Sorafenib is a protein kinase inhibitorwith activity against vascular endothelial growthfactor receptor (VEGFR), platelet derivedgrowth factor receptor (PDGFR), rearrangedduring transfection (RET) and BRAF. Lenvatinibis a MKI targeting VEGFRs, fibroblast growthfactor receptor (FGFR), PDFGR, stem cell factor receptor (KIT), and RET. Both sorafenib andlenvatinib prolonged progression-free survivalcompared with placebo in randomized phase 3trials enrolling patients with RR-DTC. Indeed,sorafenib and lenvatinib are approved and usedin daily clinical practice in several countries forpatients with RR-DTC. Unfortunately, the toxicity of these compounds could have a detrimentaleffect on the quality of life of patients. Althoughrandomized controlled trials comparing sorafenibwith lenvatinib are not available in patients withRR-DTC, their efficacy and side effect profilesappear comparable.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
