Precision treatment guided by patient-derived organoids-based drug testing for locally advanced thyroid cancer: a single arm, phase 2 study.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2025-04-30 DOI:10.1007/s12020-025-04240-9

Ziliang Guo, Jiaye Liu, Xinyue Zhang, Yu Ma, Yichao Wang, Peng Li, Rui Huang, Zhihui Li

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引用次数: 0

Abstract

Purpose: 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.

Methods: 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).

Results: 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).

Conclusions: 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.

Trial registration: The study was registered at ClinicalTrials.gov (NCT06482086) on 06/25/2024.

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局部晚期甲状腺癌患者源性类器官药物检测指导下的精准治疗：单组2期研究

目的：局部晚期甲状腺癌（LATC）手术难度大，切除不全风险高，预后差。患者源性类器官（PDOs）是评估个体药物敏感性和建议新的治疗方案或重新挑战的有力工具。本研究旨在评价该方法应用于LATC患者的可行性和有效性。方法：在这项单组2期研究中，我们招募了75例LATC患者。用类器官模型培养原发肿瘤或转移部位的活检组织。敏感性测试是通过使用pdo和一组在II期或III期试验中证明具有活性的药物来进行的。在研究者考虑毒性的自由裁量权下，提供相对活性最高的药物。主要终点为客观缓解率（ORR）。结果：55例患者接受了至少一剂推荐药物，18例患者的主要终点达到客观缓解，总体ORR为32.7% （95% CI 20.7-46.7）。根据预先定义的不同组织学亚型亚组，分化型甲状腺癌、甲状腺髓样癌、间变性甲状腺癌患者的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）。结论：本研究首次验证了PDOs和体外敏感性试验对LATC的可行性。基于pdo的新辅助治疗有望改善预后并为这些患者提供手术机会。试验注册：该研究于2024年6月25日在ClinicalTrials.gov （NCT06482086）注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.