Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center, Heidelberg, Germany.
BMC Cancer. 2024 Apr 25;24(1):526. doi: 10.1186/s12885-024-12261-2.
Panel gene sequencing is an established diagnostic tool for precision oncology of solid tumors, but its utility for the treatment of cancers of the digestive system in clinical routine is less well documented.
We retrospectively identified patients with advanced or metastatic gastrointestinal, pancreaticobiliary or hepatic cancers who received panel gene sequencing at a tertiary university hospital from 2015 to 2022. For these cases, we determined the spectrum of genetic alterations, clinicopathological parameters and treatment courses. Assessment of actionability of genetic alterations was based on the OncoKB database, cancer-specific ESMO treatment guidelines, and recommendations of the local molecular tumor board.
In total, 155 patients received panel gene sequencing using either the Oncomine Focus (62 cases), Comprehensive (91 cases) or Childhood Cancer Research Assay (2 cases). The mean age of patients was 61 years (range 24-90) and 37% were female. Most patients suffered from either colorectal cancer (53%) or cholangiocellular carcinoma (19%). 327 genetic alterations were discovered in 123 tumor samples, with an average number of 2.1 alterations per tumor. The most frequently altered genes were TP53, KRAS and PIK3CA. Actionable gene alterations were detected in 13.5-56.8% of tumors, according to ESMO guidelines or the OncoKB database, respectively. Thirteen patients were treated with targeted therapies based on identified molecular alterations, with a median progression-free survival of 8.8 months.
Actionable genetic alterations are frequently detected by panel gene sequencing in patients with advanced cancers of the digestive tract, providing clinical benefit in selected cases. However, for the majority of identified actionable alterations, sufficient clinical evidence for targeted treatments is still lacking.
panel 基因测序是实体瘤精准肿瘤学的一种既定诊断工具，但它在临床常规中用于消化系统癌症治疗的效用记录较少。
我们回顾性地确定了 2015 年至 2022 年在一所三级大学医院接受 panel 基因测序的晚期或转移性胃肠道、胰腺胆道或肝部癌症患者。对于这些病例，我们确定了基因改变的谱、临床病理参数和治疗过程。遗传改变的可操作性评估基于 OncoKB 数据库、癌症特异性 ESMO 治疗指南以及当地分子肿瘤委员会的建议。
共有 155 名患者使用 Oncomine Focus（62 例）、Comprehensive（91 例）或 Childhood Cancer Research Assay（2 例）进行了 panel 基因测序。患者的平均年龄为 61 岁（范围 24-90 岁），其中 37%为女性。大多数患者患有结直肠癌（53%）或胆管细胞癌（19%）。在 123 个肿瘤样本中发现了 327 个基因改变，每个肿瘤的平均改变数为 2.1 个。最常改变的基因是 TP53、KRAS 和 PIK3CA。根据 ESMO 指南或 OncoKB 数据库，分别有 13.5-56.8%的肿瘤存在可操作的基因改变。根据鉴定的分子改变，有 13 名患者接受了靶向治疗，中位无进展生存期为 8.8 个月。
在晚期消化系统癌症患者中，通过 panel 基因测序经常可以检测到可操作的遗传改变，为某些病例提供了临床获益。然而，对于大多数鉴定出的可操作改变，针对靶向治疗的充分临床证据仍然缺乏。
