PDF(Pubmed)
Abstract：
Treating advanced thyroid cancer presents challenges due to its resistance to various treatment modalities, thereby limiting therapeutic options. To our knowledge, this study is the first to report the efficacy of temsirolimus in conjunction with dual immunotherapy of nivolumab/ipilimumab to treat heavily treated advanced PDTC. A 50-year-old female initially presented with a rapidly enlarging mass on her right neck. Subsequent diagnosis revealed poorly differentiated thyroid carcinoma, leading to a total thyroidectomy followed by post-operative radioablation therapy. After four years, an examination for persistent cough revealed a recurrence of the disease within multiple mediastinal nodes. Genetic analysis of blood samples uncovered somatic mutations in the tumor, specifically involving PTEN and TP53. The disease progressed despite palliative radiation, lenvatinib, and nivolumab/ipilimumab therapy. Consequently, temsirolimus, functioning as an mTOR inhibitor, was introduced as an adjunct to the nivolumab/ipilimumab regimen. This combination approach yielded remarkable clinical improvement and disease control for a duration of approximately six months. Temsirolimus likely suppressed the aberrantly activated PI3K/AKT/mTOR signaling pathway, facilitated by the PTEN genetic alteration, thus engendering an effective treatment response. This synergy between targeted agents and immunotherapy presents a promising therapeutic strategy for advanced PDTC patients with limited treatment alternatives. In previous clinical trials, mTOR inhibitors have demonstrated the ability to maintain stable disease (SD) in 65% to 74% for advanced thyroid cancer patients, including those with PDTC. When combined with other targeted therapies, the observed SD or partial response rates range from 80% to 97%. Many of these trials primarily involved differentiated thyroid carcinoma, with diverse genetic mutations. Thyroid cancer patients with alterations in the PI3K/mTOR/Akt appeared to benefit most from mTOR inhibitors. However, no clear association between the efficacy of mTOR inhibitors and specific histologies or genetic mutations has been established. Future studies are warranted to elucidate these associations.
摘要：
治疗晚期甲状腺癌由于其对各种治疗方式的抵抗力而面临挑战，从而限制了治疗选择。据我们所知,这项研究首次报道了替西罗莫司联合纳武单抗/ipilimumab双重免疫疗法治疗重度治疗的晚期PDTC的疗效.一名50岁的女性最初表现为右脖子上的肿块迅速扩大。随后的诊断显示低分化甲状腺癌，导致甲状腺全切除术，然后进行术后放射消融治疗。四年后,对持续性咳嗽的检查显示该疾病在多个纵隔淋巴结中复发。血液样本的遗传分析发现了肿瘤中的体细胞突变，特别涉及PTEN和TP53。尽管有姑息性辐射，疾病还是进展了，lenvatinib,和nivolumab/ipilimumab治疗。因此,替西罗莫司,作为mTOR抑制剂，作为nivolumab/ipilimumab方案的辅助手段。这种组合方法在大约六个月的持续时间内产生了显着的临床改善和疾病控制。坦西罗莫司可能抑制异常激活的PI3K/AKT/mTOR信号通路，由PTEN基因改变促进，从而产生有效的治疗反应。靶向药物和免疫疗法之间的这种协同作用为具有有限治疗选择的晚期PDTC患者提供了有希望的治疗策略。在之前的临床试验中,mTOR抑制剂已证明有能力在65％至74％的晚期甲状腺癌患者中维持稳定的疾病（SD），包括PDTC。当与其他靶向治疗相结合时，观察到的SD或部分缓解率范围为80％至97％。许多试验主要涉及分化型甲状腺癌,具有不同的基因突变。PI3K/mTOR/Akt改变的甲状腺癌患者似乎最受益于mTOR抑制剂。然而,mTOR抑制剂的疗效与特定组织学或基因突变之间没有明确关联.未来的研究有必要阐明这些关联。
