Aims

Medication for advanced sarcomas has not improved for three decades. Patient-derived tumour xenografts (PDTX) are a promising solution for developing new therapies and real-time personalised medicine because of their highly effective prediction of drug efficacy. However, there is a dearth of PDTX models for sarcomas due to the scarcity and heterogeneity of the disease.

Materials and methods

A multicentre clinical collaborative study (ChiCTR–OOC–17013617) was carried out. Fresh patient tumour tissues via resection or biopsy were used for the PDTX set-up. The standard medical care chosen by the physician was given to the patient, in parallel with testing on multiple regimens. The outcomes of patients' responses and PDTX tests were compared. Comprehensive analyses were carried out to assess the clinical value of PDTX for the treatment of sarcomas. Living tissues from successfully engrafted cases were deposited into a repository.

Results

Forty-two cases, including 36 bone sarcomas and six soft-tissue sarcomas, were enrolled; the overall engraftment rate was 73.8%. Histopathological examination showed a 100% consistency between primary tumours and tumour grafts. The engraftment rate was independent of age, gender and sampling methods, but was associated with subtypes of tumour. The outgrowth time of tumour grafts could be associated with prognosis. Major somatic mutations in tumour grafts occurred primarily in common tumour driver genes. Poor prognosis was associated with the KMT2C mutation. A drug efficacy test showed complete concordance between the PDTX model and patients' responses in 17 regimens.

Conclusion

PDTX is an ideal preclinical model for sarcomas because of its faithful preservation of the heterogeneity of the disease, a satisfactory engraftment rate and high accuracy in its prediction of drug efficacy.

中文翻译：

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使用患者来源的肿瘤异种移植物进行肉瘤个性化治疗的多中心临床研究

宗旨

三十年来，晚期肉瘤的药物治疗一直没有改善。患者来源的肿瘤异种移植物 (PDTX) 是开发新疗法和实时个性化医疗的有前途的解决方案，因为它们对药物疗效的预测非常有效。然而，由于疾病的稀缺性和异质性，肉瘤的 PDTX 模型很少。

材料和方法

开展了一项多中心临床协作研究 (ChiCTR–OOC–17013617)。通过切除或活检获得的新鲜患者肿瘤组织用于 PDTX 设置。医生选择的标准医疗护理被给予患者，同时对多种治疗方案进行了测试。比较了患者的反应和 PDTX 测试的结果。进行综合分析以评估 PDTX 治疗肉瘤的临床价值。来自成功植入病例的活体组织被存放到一个储存库中。

结果

共纳入42 例，包括 36 例骨肉瘤和 6 例软组织肉瘤；总体植入率为73.8%。组织病理学检查显示原发肿瘤和肿瘤移植物之间具有 100% 的一致性。植入率与年龄、性别和取样方法无关，但与肿瘤亚型有关。肿瘤移植物的生长时间可能与预后相关。肿瘤移植物中的主要体细胞突变主要发生在常见的肿瘤驱动基因中。预后不良与 KMT2C 突变有关。药物疗效测试显示 PDTX 模型与患者在 17 种方案中的反应完全一致。

结论

PDTX 是一种理想的肉瘤临床前模型，因为它忠实地保留了疾病的异质性，令人满意的植入率和预测药物疗效的准确性很高。