国家癌症研究所-儿童肿瘤组儿科MATCH 试验中难治性癌症儿科和青年患者的可操作肿瘤改变和治疗方案入组。
Actionable Tumor Alterations and Treatment Protocol Enrollment of Pediatric and Young Adult Patients With Refractory Cancers in the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial.
机构信息
Texas Children's Cancer and Hematology Center, Baylor College of Medicine, Houston, TX.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
出版信息
J Clin Oncol. 2022 Jul 10;40(20):2224-2234. doi: 10.1200/JCO.21.02838. Epub 2022 Mar 30.
PURPOSE
The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial aimed to facilitate evaluation of molecular-targeted therapies in biomarker-selected cohorts of childhood and young adult patients with cancer by screening tumors for actionable alterations.
PATIENTS AND METHODS
Tumors from patients age 1-21 years with refractory solid tumors, lymphomas, or histiocytic disorders were subjected to cancer gene panel sequencing and limited immunohistochemistry to identify actionable alterations for assignment to phase II treatment arms. The rates of treatment arm assignment and enrollment were compared between clinical and demographic groups.
RESULTS
Testing was completed for 94.7% of tumors submitted. Actionable alterations were detected in 31.5% of the first 1,000 tumors screened, with treatment arm assignment and enrollment occurring in 28.4% and 13.1% of patients, respectively. Assignment rates varied by tumor histology and were higher for patients with CNS tumors or enrolled at Pediatric Early Phase Clinical Trials Network sites. A reported history of prior clinical molecular testing was associated with higher assignment and enrollment rates. Actionable alterations in the mitogen-activated protein kinase signaling pathway were most frequent (11.2%). The most common reasons provided for not enrolling on treatment arms were patients receiving other treatment or poor clinical status.
CONCLUSION
The Pediatric MATCH trial has proven the feasibility of a nationwide screening Protocol for identification of actionable genetic alterations and assignment of pediatric and young adult patients with refractory cancers to trials of molecularly targeted therapies. These data support the early use of tumor molecular screening for childhood patients with cancer whose tumors have not responded to standard treatments.
目的
美国国家癌症研究所-儿童肿瘤组儿科 MATCH 试验旨在通过对肿瘤进行靶向治疗相关改变的筛查，为儿童和青年癌症患者的生物标志物选择队列中评估分子靶向治疗提供便利。
方法
对年龄在 1-21 岁的难治性实体瘤、淋巴瘤或组织细胞疾病患者的肿瘤进行癌症基因panel 测序和有限的免疫组化检测，以确定可进行二期治疗的靶向治疗改变。比较了临床和人口统计学组之间治疗组分配和入组的比例。
结果
完成了 94.7%提交肿瘤的检测。在筛选的前 1000 个肿瘤中，有 31.5%检测到了可进行靶向治疗的改变，分别有 28.4%和 13.1%的患者接受了治疗组分配和入组。分配率因肿瘤组织学而异，中枢神经系统肿瘤患者或在儿科早期临床试验网络站点入组的患者分配率较高。报告有既往临床分子检测史与较高的分配和入组率相关。丝裂原活化蛋白激酶信号通路中的可进行靶向治疗的改变最为常见（11.2%）。未入组治疗组的最常见原因是患者正在接受其他治疗或临床状况较差。
结论
儿科 MATCH 试验已经证明了一种全国性的筛选方案的可行性，该方案用于鉴定可进行靶向治疗的遗传改变，并将难治性癌症的儿科和青年成年患者分配到分子靶向治疗的试验中。这些数据支持在儿童癌症患者的肿瘤对标准治疗无反应时尽早进行肿瘤分子筛选。
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