Pediatric Hematology/Oncology Fellow, Duke University, Durham, North Carolina, USA.
Division of Pediatric Hematology/Oncology, Roswell Park Oishei Children's Cancer and Blood Disorders Program, Buffalo, New York, USA.
Pediatr Blood Cancer. 2023 Jun;70(6):e30324. doi: 10.1002/pbc.30324. Epub 2023 Apr 5.
Although tumor genomic profiling has aided the advancement of targeted genetic therapy, its clinical integration remains a challenge in pediatric cancers due to lower mutation frequency and less available targeted drugs. There have been multiple novel studies examining molecular sequencing in pediatrics; however, many of these studies primarily utilized large-scale, genome-wide screening applications that limit applicable use due to the availability of testing. This study examined the institutional use of a targeted, clinically available approach to tumor genomic sequencing.
A retrospective chart review was performed on pediatric patients with solid tumors who were managed at Roswell Park Comprehensive Cancer Center and underwent molecular testing of their tumor biopsy via OmniSeq from August 2016 to July 2021. Results were reviewed for mutations considered to be "actionable" by targeted therapy. Patients with actionable mutations were further examined to evaluate treatment course, receival of targeted therapy, and clinical outcomes.
We identified 64 pediatric patients consisting of 20 (31%) with CNS tumors and 44 (69%) with non-CNS tumors, ranging in age from 9 months to 21 years. Thirty-five total actionable mutations were identified amongst 27 patients (42%). Of these 27, 12 patients (44%) received at least 1 targeted drug against a respective actionable mutation, of which 6 patients (50%) achieved clinical benefit to therapy, including 1 complete response.
The use of a clinically focused and readily available targeted molecular sequencing panel identified actionable mutations at a comparable rate to the large-scale, less readily available sequencing panels utilized in other studies. Half of our patients who received targeted therapy achieved a complete response or clinical benefit from therapy. Although targeted therapy has a role in pediatric cancer treatment, many newer drugs require further research on their safety and efficacy.
尽管肿瘤基因组分析有助于推进靶向基因治疗，但由于突变频率较低且可用的靶向药物较少，其在儿科癌症中的临床整合仍然具有挑战性。已经有多项研究检查了儿科中的分子测序；然而，这些研究中的许多主要使用了限制了可应用范围的大规模、全基因组筛查应用程序，因为测试的可用性。本研究检查了一种针对肿瘤基因组测序的靶向、临床可用方法的机构使用情况。
对罗切斯特大学帕克综合癌症中心管理的实体瘤儿科患者进行了回顾性图表审查，并在 2016 年 8 月至 2021 年 7 月期间通过 OmniSeq 对其肿瘤活检进行了分子检测。对被认为可通过靶向治疗“治疗”的突变进行了结果审查。进一步检查了具有可治疗突变的患者，以评估治疗过程、接受靶向治疗和临床结果。
我们确定了 64 名儿科患者，其中 20 名（31%）为中枢神经系统肿瘤，44 名（69%）为非中枢神经系统肿瘤，年龄从 9 个月到 21 岁不等。在 27 名患者中总共发现了 35 个总可治疗突变。在这 27 名患者中，有 12 名（44%）接受了至少一种针对各自可治疗突变的靶向药物，其中 6 名（50%）对治疗有临床获益，包括 1 例完全缓解。
使用针对临床的、易于获得的靶向分子测序面板以与其他研究中使用的大规模、不易获得的测序面板相当的速度识别出可治疗的突变。我们接受靶向治疗的一半患者完全缓解或从治疗中获得临床获益。尽管靶向治疗在儿科癌症治疗中具有作用，但许多新型药物需要进一步研究其安全性和有效性。
