Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, Arizona.
Departments of Cancer Biology and Neurosurgery, Mayo Clinic Arizona, Scottsdale, Arizona.
Clin Cancer Res. 2018 Jan 15;24(2):295-305. doi: 10.1158/1078-0432.CCR-17-0963. Epub 2017 Oct 26.
Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood-brain barrier penetration of the indicated therapies, drug-drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system-penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma. .
胶质母细胞瘤是一种侵袭性的、分子异质性的癌症，治疗选择有限。我们假设，在复发性胶质母细胞瘤患者手术后的可接受临床时间框架内，下一代测序可用于指导治疗建议。我们对复发性和进行性胶质母细胞瘤的成年人进行了一项前瞻性基于基因组学的可行性试验。在手术切除后，进行全基因组肿瘤/正常外显子测序和肿瘤 RNA 测序，以确定潜在匹配治疗的分子靶标。多学科分子肿瘤委员会根据基因组结果、指示治疗的血脑屏障穿透性、药物相互作用和药物安全概况发布治疗建议。评估了在手术 35 天内生成基于基因组学的治疗建议的可行性。在这项研究中，20 名患者中有 16 名患者有足够的肿瘤组织进行分析。所有患者均完成了外显子组测序，14 名患者完成了 RNA 测序。16 名患者中有 15 名（94%）在研究的可行性时间框架内提供了治疗建议。7 名患者根据肿瘤委员会的建议接受了治疗。2 名患者达到 12 个月无进展生存期，均遵循基于分子谱分析结果的治疗方法。1 名患者在手术后 21 个月仍在接受治疗且无进展，比患者之前的进展时间延长了 3 倍。对 12 名患者的匹配非增强组织进行分析，发现了重叠的、新的潜在可靶向的基因组改变。全基因组分子谱分析的使用是可行的，并且可以为复发性胶质母细胞瘤患者提供实时、穿透中枢神经系统的基于基因组学的治疗建议提供信息。
