Giannetta Elisa, Isidori Andrea M, Durante Cosimo, Di Gioia Cira, Longo Flavia, Tombolini Vincenzo, Bulzonetti Nadia, Graziadio Chiara, Pofi Riccardo, Gianfrilli Daniele, Verrienti Antonella, Carletti Raffaella, Filetti Sebastiano, Lenzi Andrea, Baroli Alberto
Department of Experimental Medicine Department of Internal Medicine and Clinical Specialities Department of Radiology, Anatomopathology and Oncology, Sapienza University of Rome, Rome Nuclear Medicine Unit, Department of Interventional Oncology, Azienda Ospedaliera Ospedale di Circolo di Busto Arsizio Varese, Busto Arsizio, Varese, Italy.
Medicine (Baltimore). 2017 Feb;96(6):e5621. doi: 10.1097/MD.0000000000005621.
The case reported the rapid remission of disease recurrence achieved adding foscarnet, a DNA polymerase inhibitor that interacts with fibroblast growth factor 2, to low molecular weight heparin and sunitinib for the first time in a patient with an anaplastic thyroid cancer (ATC).
A 65-year-old woman with a multinodular goiter referred for a rapid enlargement of a nodule. Histological examination revealed an ATC with a little area of papillary thyroid cancer (PTC). The patient was resistant to selective single-target treatment.
Immunophenotyping and gene analyses found a significant increase in FGF2 and FGFR1 expression in the primary ATC area (FGF2 = 38.2 ± 6.2% in ATC vs 34.6 ± 6.0% in the differentiated area of PTC, P < 0.05; FGFR1: 41.7 ± 6.0% in ATC vs 34.4 ± 4.2% in PTC, P < 0.001) and in metastatic neck lymph nodes (P < 0.001 vs normal control tissues). Unlike conventional imaging, F-FDG PET/CT with PERCIST 1.0 criteria promptly and quantitatively detected disease recurrence and remission before and after multitarget therapy, combining anatomic, metabolic, and functional data.
Foscarnet was administered given the positivity for FGF2, FGFR1 and FGFR4 in ATC. Low molecular wight heparin and Sunitinib were coadministere to limiti metastatic progression and on neck tumor masse, respectively.
The rationale for the clinical response to this innovative multitarget association with foscarnet is based on the histological and genetic finding that fibroblast growth factors and their receptor super-family are up-regulated in the primary anaplastic thyroid tumor and in the metastatic lymph node of our patient.
We propose that fibroblast growth factors and their receptor super-family play a key role as potential therapeutic targets in anaplastic thyroid cancer and the positive relevance of this suggestion for patient care, especially for an individualized management.
该病例首次报告了在一名间变性甲状腺癌(ATC)患者中,将与成纤维细胞生长因子2相互作用的DNA聚合酶抑制剂膦甲酸钠添加到低分子量肝素和舒尼替尼中后,疾病复发迅速缓解。
一名65岁患有多结节性甲状腺肿的女性因一个结节迅速增大前来就诊。组织学检查显示为ATC,伴有小面积的乳头状甲状腺癌(PTC)。该患者对选择性单靶点治疗耐药。
免疫表型分析和基因分析发现,在原发性ATC区域(FGF2:ATC中为38.2±6.2%,而PTC分化区域中为34.6±6.0%,P<0.05;FGFR1:ATC中为41.7±6.0%,而PTC中为34.4±4.2%,P<0.001)以及颈部转移性淋巴结中(与正常对照组织相比,P<0.001),FGF2和FGFR1表达显著增加。与传统成像不同,采用PERCIST 1.0标准的F-FDG PET/CT结合了解剖、代谢和功能数据,能迅速且定量地检测多靶点治疗前后的疾病复发和缓解情况。
鉴于ATC中FGF2、FGFR1和FGFR4呈阳性结果,给予膦甲酸钠治疗。分别联合使用低分子量肝素和舒尼替尼以限制转移进展和缩小颈部肿瘤肿块。
这种与膦甲酸钠的创新性多靶点联合治疗产生临床反应的原理基于组织学和遗传学发现,即成纤维细胞生长因子及其受体超家族在我们患者的原发性间变性甲状腺肿瘤和转移性淋巴结中上调。
我们提出成纤维细胞生长因子及其受体超家族作为间变性甲状腺癌潜在的治疗靶点发挥关键作用,以及这一建议对患者护理的积极相关性,特别是对于个体化管理。