Background: In the era of precision medicine, cancer treatment is increasingly tailored according to tumor-specific genomic alterations. The analysis of tumor-derived circulating nucleic acids in cerebrospinal fluid (CSF) by next generation sequencing (NGS) may facilitate precision medicine in the field of CNS cancer. We therefore evaluated whether NGS from CSF of neuro-oncologic patients reliably detects tumor-specific genomic alterations and whether this may help to guide the management of patients with CNS cancer in clinical practice.

Patient and methods: CSF samples from 27 patients with various primary and secondary CNS malignancies were collected and evaluated by NGS using a targeted, amplicon-based NGS-panel (Oncomine Focus Assay). All cases were discussed within the framework of a molecular tumor board at the Comprehensive Cancer Center Munich.

Results: NGS was technically successful in 23/27 patients (85%). Genomic alterations were detectable in 20/27 patients (74%), 11/27 (40%) of which were potentially actionable. After discussion in the MTB, a change of therapeutic management was recommended in 7/27 (26%) of the cases. However, due to rapid clinical progression, only 4/27 (15%) of the patients were treated according to the recommendation. In a subset of patients (6/27, 22%), a high number of mutations of unknown significance suggestive of a high tumor mutational burden (TMB) were detected.

Conclusions: NGS from cerebrospinal fluid is feasible in routine clinical practice and yields therapeutically relevant alterations in a large subset of patients. Integration of this approach into a precision cancer medicine program might help to improve therapeutic options for patients with CNS cancer.

背景：在精密医学时代，癌症治疗越来越多地根据肿瘤特异性基因组改变量身定制。通过下一代测序（NGS）分析脑脊液（CSF）中的肿瘤衍生循环核酸可能有助于CNS癌症领域的精密医学。因此，我们评估了神经肿瘤患者脑脊液中的NGS是否能可靠地检测出肿瘤特异性基因组改变，以及这是否有助于在临床实践中指导中枢神经系统癌症患者的治疗。

患者和方法：收集27例患有各种原发性和继发性中枢神经系统恶性肿瘤的患者的CSF样本，并使用靶向的，基于扩增子的NGS面板（Oncomine Focus Assay）通过NGS进行评估。所有病例均在慕尼黑综合癌症中心的分子肿瘤委员会的框架内进行了讨论。

结果：NGS在23/27例患者中技术成功（85％）。在20/27例患者（74％）中可检测到基因组改变，其中11/27例（40％）具有潜在作用。在MTB中进行讨论后，在7/27（26％）的病例中建议改变治疗方法。但是，由于临床进展迅速，根据建议仅治疗了4/27（15％）的患者。在一部分患者中（6/27，22％），检测到大量突变，其重要性不明，提示存在高的肿瘤突变负担（TMB）。

结论：脑脊液中的NGS在常规临床实践中是可行的，并在很大一部分患者中产生与治疗相关的改变。将此方法整合到精确的癌症医学计划中可能有助于改善CNS癌症患者的治疗选择。