Clinicopathological Features Predict Outcomes in Patients with Radioiodine‐Refractory Differentiated Thyroid Cancer Treated with Sorafenib: A Real‐World Study

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Abstract

Because beneficial response and progression‐free survival (PFS) were achieved by well‐designed clinical trials with tyrosine kinase inhibitors (TKIs) in patients with progressive radioiodine‐refractory differentiated thyroid cancer (RR‐DTC), the overall survival (OS) and improvement of therapeutic outcomes in the real world have been anticipated. This prospective, single‐center, real‐world study assessed the predictive significance of clinicopathological features on disease control rate (DCR), objective response rate (ORR), PFS, and OS in a cohort of 72 patients with progressive RR‐DTC treated with sorafenib at an initial dose of 200 mg twice daily. Disease control, objective response, and biochemical effectiveness were achieved in 73.3%, 21.7%, and 77.9% of patients, respectively. The median PFS and OS were 17.6 and 28.9 months, respectively. Multivariate analyses showed that hand‐foot syndrome (HFS) was an independent predictor for better DCR and ORR, and 131 I‐avidity for higher ORR. In univariate analyses, longer PFS and OS were observed in patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, pathologically well DTC, lung‐only metastasis, absence of bone metastasis, biochemically nonineffective response, HFS, or radiological disease control. In multivariate analyses, only well DTC and ECOG PS ≤2 remained as independent prognostic factors for more favorable PFS and OS, respectively, whereas the absence of bone metastasis and biochemically nonineffective response independently predicted superior PFS and OS. This study demonstrated that clinicopathological features might play a vital role in predicting therapeutic outcomes in patients with progressive RR‐DTC treated with sorafenib, warranting further optimization of candidates for TKIs. This prospective, single‐center, real‐world study was designed to investigate the significance of clinicopathological features in predicting response, progression‐free survival, and overall survival in patients with progressive radioiodine‐refractory differentiated thyroid cancer (DTC) treated with sorafenib. Multivariate analyses showed that hand‐foot syndrome was an independent predictor for better response. Meanwhile, well DTC, Eastern Cooperative Oncology Group performance status ≤2, biochemically nonineffective response, and the absence of bone metastasis were independent prognostic factors for more favorable survival. This study demonstrated that clinicopathological features might play a vital role in predicting outcomes in sorafenib‐treated patients with radioiodine‐refractory DTC, warranting optimization of indications. Thyroid cancer is the most common endocrine malignancy. This article reports results of a study that investigated the significance of clinicpoathological features in predicting response and survival rates in patients with progressive radioiodine‐refractory differentiated thyroid cancer treated with sorafenib.

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Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines.

Kymberleigh A. Romano, G Viglietto, M Rambaldi … (1995)

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies. Placenta growth factor (PlGF) is a recently identified growth factor for endothelial cells (EC); PlGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PlGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors. We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines. Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas. Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PlGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors. Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.