中国实用外科杂志

中国实用外科杂志 ›› 2023, Vol. 43 ›› Issue (08): 894-899.DOI: 10.19538/j.cjps.issn1005-2208.2023.08.13

• 论著 • 上一篇    下一篇

基于肿瘤类器官指导局部进展期甲状腺乳头状癌临床个性化治疗可行性研究

郭子良，张歆玥，刘嘉烨，李志辉   

  1. 四川大学华西医院甲状腺外科，四川成都 610041 
  • 出版日期:2023-08-01 发布日期:2023-08-24

  • Online:2023-08-01 Published:2023-08-24

摘要： 目的    通过建立甲状腺乳头状癌（PTC）病人来源的肿瘤类器官生物样本库，于体外模拟PTC的生物学行为，探讨肿瘤类器官作为临床前模型指导局部进展期PTC病人靶向治疗的可行性。方法    收集2021年2月至2022年8月在四川大学华西医院甲状腺外科就诊的27例局部进展期PTC病人的肿瘤组织，分离培养PTC类器官，并对PTC类器官进行组织形态学评估，进一步用不同的靶向药物处理PTC类器官，用CellTiter-Glo检测类器官对靶向药物的敏感性，并与临床疗效匹配。结果    27例病人中，共成功建立22例（81.5%）PTC类器官，均为通过穿刺从PTC病人肿瘤组织中建立。经过连续传代的PTC类器官仍保持与原始肿瘤组织的形态学一致。病人来源的PTC类器官与对应病人临床疗效的总体一致率为86.4%（19/22）。PTC类器官药敏试验显示敏感的病人部分缓解（PR）率及疾病稳定（SD）率分别为41.7%、58.3%。PTC类器官药敏试验显示耐药的病人PR、SD及疾病进展（PD）率分别为12.5%、37.5%、50.0%。PTC类器官药敏试验显示敏感及耐药病人的中位无进展生存期（PFS）分别为10个月（95%CI 8.2-11.8）、4个月（95%CI 2.6-5.4），差异有统计学意义（P＜0.001）。结论    通过将临床实际疗效与PTC类器官药敏试验结果进行比对分析，证实将PTC类器官作为临床前试验模型制定靶向治疗方案、预判临床疗效具有可行性。

关键词: 甲状腺乳头状癌, 局部进展期甲状腺癌, 靶向治疗, 类器官

Abstract: Feasibility study of clinical personalized treatment guided by tumor organoids in locally advanced papillary carcinoma        GUO Zi-liang, ZHANG Xin-yue, LIU Jia-ye, et al.Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu 610000,China
Corresponding author：LI Zhi-hui, E-mail:rockoliver@vip.sina.com
Abstract    Objective    To study the feasibility of using tumor organoids as preclinical models to guide targeted therapy of locally advanced papillary thyroid carcinoma(PTC) patients by establishing a tumor organoid biobank from patients with PTC and simulate the biological behavior of PTC in vitro. Methods    A total of 27 patients with locally advanced PTC who were treated in the Department of Thyroid Surgery, West China Hospital, Sichuan University from February 2021 to August 2022 were collected and their tumor tissues were collected to isolate and culture PTC organoids, and the PTC organoids were evaluated by histomorphology, and further treated with different targeted drugs. CellTiter-Glo was used to detect the sensitivity of organoids to targeted drugs, and matched with clinical efficacy. Results    A total of 22 PTC organoids were successfully established from thyroid cancer patients by thyroid aspiration. After successive generations, the PTC organoids remained morphologically consistent with the original tumor tissue. The clinical efficacy of patient-derived PTC organoids was 86.4% consistent with that of corresponding patients. The partial response (PR) and stable disease (SD) rates of patients in the drug-sensitive group were 41.7% and 58.3%, respectively. The PR, SD and disease progression (PD) rates of patients in the drug-resistant group were 12.5%, 37.5% and 50.0%, respectively. The median progression-free survival(PFS) of patients in the two groups was 10 (95% CI 8.2-11.8) and 4 (95% CI 2.6-5.4) months, respectively, which was statistically different (P < 0.001). Conclusion    It is feasible to use PTC organoids as a preclinical experimental model to develop targeted therapy and predict clinical efficacy by comparing the actual clinical efficacy with the results of drug sensitivity experiments on PTC organoids.

Key words: papillary thyroid carcinoma, locally advanced thyroid carcinoma, targeted therapy, organoid