PO.CL06.03 · 临床研究
儿童精准癌症医学时代分子匹配靶向治疗的真实世界治疗：取得进展还是缓慢前行？
Real world treatment with molecularly matched targeted therapies in the era of pediatric precision cancer medicine: Gaining ground or inching forward?
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摘要 Abstract
中文摘要
引言：诊断为复发/难治性或高危癌症的儿童和青少年预后不良，复发性疾病患者的生存率<20%。已建立了多个儿童精准癌症医学项目，以指导临床决策并为有需要的患者提供分子匹配的治疗选择。然而，这些疗法在真实世界环境中的临床获益尚不明确。我们对文献以及在哥伦比亚大学医学中心（CUMC）通过儿童精准测序（PIPseq）项目进行测序的患者进行了回顾，以描述接受分子匹配靶向治疗（MTT）的实体瘤或CNS肿瘤患者的结局。
方法：回顾了2013-2025年间的PubMed和CUMC病历。提取了诊断为高危或复发/难治性疾病患者的患者水平分子和治疗数据。评估了临床获益率（CBR）（完全缓解（CR）、部分缓解（PR）以及疾病稳定（SD）持续≥6个月的百分比）。采用log-rank检验评估无进展生存期（PFS）和总生存期（OS）的差异。
结果：共识别出20项研究和29例PIPseq患者。纳入233例CNS肿瘤和394例实体瘤（ST）患者。40%（CNS）、23%（ST）和总体30%的患者获得临床获益。低级别胶质瘤患者的CBR最高（69%，n=36），髓母细胞瘤的CBR最低（20%，n=20）。最大的CNS队列高级别胶质瘤的CBR为（25%，n=122）。部分ST亚型的CBR分别为16%（肾上腺，n=81）、11%（骨肉瘤，n=65）、16%（横纹肌肉瘤，n=55）和12%（尤因肉瘤，n=33）。进行了Kaplan-Meier生存分析，以比较不同治疗类别（MTT单药、多药MTT和MTT+化疗）的生存分布。按治疗类别，CNS患者（n=166/138）的中位PFS/OS分别为5.5/32.1、14/32.2和4.8/24个月。Log-rank检验显示PFS有显著差异/OS无显著差异，X2(2)=7.45/1.12，p=.025/.571，估计中位随访时间为28/32.1个月。ST患者（n=263/179）按治疗类别的中位PFS/OS时间分别为4.2/11.6、1.7/32.3和4.1/13.7个月，生存差异无统计学意义，X2(2)=4.1/1.72，p=.129/.423。估计中位随访时间为22.8/28.2个月。
结论：总体而言，30%接受MTT治疗的患者获得临床获益。CNS患者的PFS存在显著差异但OS无差异，其中多药MTT相比MTT单药或MTT+化疗产生最长的PFS和OS。治疗方式未显示ST患者生存的显著差异。需要超过2年的更长随访以评估接受MTT治疗的儿童患者的生存情况。
查看英文原文 English abstract
Introduction: Children and adolescents diagnosed with relapsed/refractory or high-risk cancer have a poor prognosis and <20% survival rates for those with recurrent disease. Several pediatric precision cancer medicine programs have been established to inform clinical decision making and provide molecularly matched therapeutic options for patients in need. However, the clinical benefit of these therapies in real-world settings is unknown. A review of the literature and patients sequenced through the Precision in Pediatric Sequencing (PIPseq) program at Columbia University Medical Center (CUMC) was conducted to describe outcomes of patients with solid or CNS tumors treated with a molecularly matched targeted therapy (MTT).
Methods: PubMed and the CUMC medical record were reviewed between 2013-2025. Patient-level molecular and treatment data were extracted for those diagnosed with high-risk or relapsed/refractory disease. Clinical benefit rate (CBR) (percent complete response (CR), partial response (PR), and stable disease (SD) for >/= 6 months) was evaluated. Progression free (PFS) and overall survival (OS) differences were assessed using the log-rank test.
Results: 20 studies and 29 PIPseq patients were identified. 233 CNS and 394 solid tumor (ST) patients were included. 40% (CNS), 23% (ST) and 30% overall derived clinical benefit. Patients with low grade glioma had the highest CBR (69%, n = 36) and medulloblastoma had the lowest CBR (20%, n = 20). CBR for the largest CNS cohort, high grade glioma, was (25%, n = 122). CBR for select ST subtypes were 16% (adrenal, n = 81), 11% (osteosarcoma, n = 65), 16% (rhabdomyosarcoma, n = 55) and 12% (Ewing sarcoma, n = 33). Kaplan-Meier survival analysis was conducted to compare survival distributions across treatment categories, MTT monotherapy, multi agent MTT, and MTT+chemotherapy. By treatment category, median PFS/OS for CNS patients (n = 166/138) were 5.5/32.1, 14/32.2, and 4.8/24 months, respectively. Log-rank tests indicated a significant PFS/non-significant OS difference, X 2 (2) = 7.45/1.12, p = .025/.571 with an estimated median follow-up of 28/32.1 months. Median PFS/OS times for ST patients (n = 263/179) by treatment category were 4.2/11.6, 1.7/32.3, and 4.1/13.7 months, respectively with non-significant differences in survival, X 2 (2) = 4.1/1.72, p = .129/.423. The estimated median follow-up was 22.8/28.2 months.
Conclusions: Overall, 30% of patients treated with MTT derived clinical benefit. There was a significant difference in PFS but not OS for CNS patients with multiagent MTT yielding the longest PFS and OS compared to MTT monotherapy or MTT+chemotherapy. Treatment modality did not reveal a significant difference in survival for ST patients. Longer follow up beyond 2 years is needed to assess survival in pediatric patients treated with MTT.
利益披露 Disclosure
J. A. Oberg, None.