Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL, United States.
Front Endocrinol (Lausanne). 2024 Jan 31;15:1304188. doi: 10.3389/fendo.2024.1304188. eCollection 2024.
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 and . 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.
治疗晚期甲状腺癌具有挑战性，因为它对各种治疗方式具有耐药性，从而限制了治疗选择。据我们所知，这项研究首次报告了替西罗莫司联合纳武利尤单抗/伊匹单抗双重免疫治疗治疗经大量治疗的晚期 PDTC 的疗效。一名 50 岁女性最初出现右侧颈部迅速增大的肿块。随后的诊断显示为低分化甲状腺癌，导致全甲状腺切除术和术后放射性消融治疗。四年后，因持续性咳嗽检查发现疾病在多个纵隔淋巴结内复发。血液样本的基因分析显示肿瘤存在体细胞突变，特别是涉及 和 。尽管进行了姑息性放疗、仑伐替尼和纳武利尤单抗/伊匹单抗治疗，但疾病仍在进展。因此，替西罗莫司作为 mTOR 抑制剂被引入纳武利尤单抗/伊匹单抗方案中作为辅助治疗。这种联合治疗方法产生了显著的临床改善和疾病控制，持续了大约六个月。替西罗莫司可能通过 PTEN 基因改变抑制了异常激活的 PI3K/AKT/mTOR 信号通路，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治疗选择有限的晚期 PDTC 患者提供了一种有前途的治疗策略。在以前的临床试验中，mTOR 抑制剂已证明能够使包括 PDTC 在内的晚期甲状腺癌患者的疾病稳定（SD）率维持在 65%至 74%。当与其他靶向治疗联合使用时，观察到的 SD 或部分缓解率范围为 80%至 97%。这些试验主要涉及分化型甲状腺癌，具有多种基因突变。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的关联。需要进一步的研究来阐明这些关联。
