Liang Muh-Lii, Yeh Ting-Chi, Huang Man-Hsu, Wu Pao-Shu, Wu Shih-Pei, Huang Chun-Chao, Yen Tsung-Yu, Ting Wei-Hsin, Hou Jen-Yin, Huang Jia-Yun, Ding Yi-Huei, Zheng Jia-Huei, Liu Hsi-Che, Ho Che-Sheng, Chen Shiu-Jau, Hsieh Tsung-Han
Department of Neurosurgery, MacKay Memorial Hospital, Taipei 104, Taiwan.
Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan.
Diagnostics (Basel). 2023 Mar 24;13(7):1232. doi: 10.3390/diagnostics13071232.
Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.
原发性颅内室管膜瘤是一种难以治疗的肿瘤，尽管有包括手术切除、放疗和辅助化疗在内的多学科治疗方法。初始治疗完成后，当耐药肿瘤细胞复发时，需要采用更精确的策略进行挽救治疗。循环肿瘤细胞（CTC）已在原发性或复发性弥漫性胶质瘤患者中得到特异性检测和验证。CTC药物筛选平台可用于进行微创液体活检以选择潜在药物。基于同一患者的患者来源异种移植（PDX）小鼠模型中潜在药物的验证可作为临床前测试平台。在此，我们展示了一种药物测试模型在一名六岁患有后颅窝A型原发性室管膜瘤（EPN-PFA）女孩中的应用。她在首次手术后2年出现肿瘤复发并伴有颅内和脊髓播散，在初始治疗后4年出现胸膜、肺、纵隔和远处股骨的神经外转移。CTC筛选平台结果显示，依维莫司和恩曲替尼可用于降低CTC活力。这两种治疗药物的疗效也在来自同一患者的PDX小鼠模型中得到验证，结果表明这两种治疗药物显著降低了肿瘤生长。在精确的药物筛选以及对股骨进行局部放疗并联合依维莫司化疗后，全身骨扫描显示右股骨转移瘤明显缩小。这种新方法可以将液体活检、CTC药物测试平台和PDX模型验证相结合，以实现对伴有神经外转移的罕见且具有挑战性的肿瘤的精准医疗。
