Guo Ziliang, Liu Jiaye, Zhang Xinyue, Ma Yu, Wang Yichao, Li Peng, Huang Rui, Li Zhihui
Division of Thyroid Surgery, Department of General Surgery; Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610000, China.
Department of Respiratory and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610000, China.
Endocrine. 2025 Apr 30. doi: 10.1007/s12020-025-04240-9.
Locally advanced thyroid cancer (LATC) presents significant surgical challenges, with a high risk of incomplete resection and poor prognosis. Patient-derived organoids (PDOs) are a powerful tool to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. This study aimed to evaluate the method's feasibility and efficacy as applied to patients with LATC.
In this single arm, phase 2 study, we enrolled 75 patients with LATC. Biopsies from the primary tumor or metastatic site were cultured using organoid models. Sensitivity testing was performed by using PDOs with a panel of drugs with proven activity in phase II or III trials. At the discretion of the investigator considering toxicity, the drug with the highest relative activity was offered. The primary endpoint was the objective response rate (ORR).
Fifty-five patients received at least one dose of recommended drug and the primary endpoint, objective response was met in 18 patients with an overall ORR as 32.7% (95% CI 20.7-46.7). Based on the pre-defined subgroups of different histological subtypes, the ORR for patients with differentiated thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer were 32.6%, (95% CI 19.1-48.5), 16.7% (95% CI 0.4-64.1) and 50% (95% CI 11.8-88.2), respectively. The R0/R1 resection rate was 34.5% (19/55).
This study is the first to validate the feasibility of PDOs and in vitro sensitivity testing for LATC. PDO-based neoadjuvant therapy holds promise in improving prognosis and providing surgical opportunities for these patients.
The study was registered at ClinicalTrials.gov (NCT06482086) on 06/25/2024.
局部晚期甲状腺癌（LATC）带来了重大的手术挑战，存在不完全切除的高风险且预后较差。患者来源的类器官（PDO）是在个体水平评估药物敏感性以及提出新治疗方案或再次挑战的有力工具。本研究旨在评估该方法应用于LATC患者的可行性和疗效。
在这项单臂2期研究中，我们纳入了75例LATC患者。使用类器官模型培养来自原发性肿瘤或转移部位的活检组织。通过将PDO与一组在II期或III期试验中已证实有活性的药物进行敏感性测试。根据研究者对毒性的考虑，提供相对活性最高的药物。主要终点是客观缓解率（ORR）。
55例患者接受了至少一剂推荐药物，18例患者达到主要终点客观缓解，总体ORR为32.7%（95%CI 20.7 - 46.7）。基于不同组织学亚型的预定义亚组，分化型甲状腺癌、髓样甲状腺癌、未分化甲状腺癌患者的ORR分别为32.6%（95%CI 19.1 - 48.5）、16.7%（95%CI 0.4 - 64.1）和50%（95%CI 11.8 - 88.2）。R0/R1切除率为34.5%（19/55）。
本研究首次验证了PDO及LATC体外敏感性测试的可行性。基于PDO的新辅助治疗有望改善这些患者的预后并提供手术机会。
该研究于2024年6月25日在ClinicalTrials.gov（NCT06482086）注册。
