UCSF Benioff Children's Hospital & University of California San Francisco, San Francisco, California.
Dana-Farber Cancer Institute, Boston, Massachusetts.
Neuro Oncol. 2018 Oct 9;20(11):1547-1555. doi: 10.1093/neuonc/noy070.
Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets.
Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment.
Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%-97%).
Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.
弥漫性内生脑桥胶质瘤（DIPG）的诊断依赖于影像学研究，因为其表现具有特征性，而且手术风险被认为很高，且不太可能影响治疗。本报告的 DIPG 生物学和治疗研究（DIPG-BATS）纳入了初诊时的手术活检，并对受试者进行分层，根据特定的生物学靶点选择接受 FDA 批准的药物。
如果新诊断肿瘤的临床特征和影像学表现符合 DIPG，则符合本试验的纳入标准。在入组后和确定治疗前进行手术活检。所有受试者均接受贝伐珠单抗联合常规外照射放疗治疗，然后根据 O6-甲基鸟嘌呤-DNA 甲基转移酶状态和表皮生长因子受体表达情况，分层接受贝伐珠单抗联合厄洛替尼或替莫唑胺、两者联合或两者均不联合的治疗。进行了全基因组测序和 RNA 测序，但未用于治疗分配。
23 家机构共纳入 53 例患者，其中 50 例行活检。中位年龄为 6.4 岁，24 例男性，29 例女性。采用特定技术进行手术活检，无手术相关死亡。2 例患者在手术过程中出现 3 级毒性（呼吸暂停 1 例，高血压 1 例）。1 例患者出现神经系统缺陷（左侧偏瘫），未完全恢复。在 50 例活检肿瘤中，46 例提供了足够的组织进行研究检测（92%，两阶段精确二项式 90%CI：83%-97%）。
DIPG 的手术活检在技术上是可行的，风险可接受，并且可以提供生物学数据，为治疗决策提供信息。
