Szkukalek Judita, Dóczi Róbert, Dirner Anna, Boldizsár Ákos, Varga Ágnes, Déri Júlia, Lakatos Dóra, Tihanyi Dóra, Vodicska Barbara, Schwáb Richárd, Pajkos Gábor, Várkondi Edit, Vályi-Nagy István, Valtinyi Dorottya, Nagy Zsuzsanna, Peták István
Department of Clinical Oncology, St. Imre Hospital, 1115 Budapest, Hungary.
Oncompass Medicine Hungary Ltd., 1024 Budapest, Hungary.
Diagnostics (Basel). 2021 Oct 7;11(10):1850. doi: 10.3390/diagnostics11101850.
We present the case of a 50-year-old female whose metastatic pancreatic neuroendocrine tumor (pNET) diagnosis was delayed by the COVID-19 pandemic. The patient was in critical condition at the time of diagnosis due to the extensive tumor burden and failing liver functions. The clinical dilemma was to choose between two registered first-line molecularly-targeted agents (MTAs), sunitinib or everolimus, or to use chemotherapy to quickly reduce tumor burden.
Cell-free DNA (cfDNA) from liquid biopsy was analyzed by next generation sequencing (NGS) using a comprehensive 591-gene panel. Next, a computational method, digital drug-assignment (DDA) was deployed for rapid clinical decision support.
NGS analysis identified 38 genetic alterations. DDA identified 6 potential drivers, 24 targets, and 79 MTAs. Everolimus was chosen for first-line therapy based on supporting molecular evidence and the highest DDA ranking among therapies registered in this tumor type. The patient's general condition and liver functions rapidly improved, and CT control revealed partial response in the lymph nodes and stable disease elsewhere.
Deployment of precision oncology using liquid biopsy, comprehensive molecular profiling, and DDA make personalized first-line therapy of advanced pNET feasible in clinical settings.
我们报告了一例50岁女性患者，其转移性胰腺神经内分泌肿瘤（pNET）的诊断因新冠疫情而延迟。由于肿瘤负荷广泛且肝功能衰竭，患者在诊断时情况危急。临床面临的困境是在两种已注册的一线分子靶向药物（MTA）舒尼替尼或依维莫司之间进行选择，还是使用化疗来迅速减轻肿瘤负荷。
利用包含591个基因的综合基因panel，通过下一代测序（NGS）对液体活检中的游离DNA（cfDNA）进行分析。接下来，采用一种计算方法——数字药物分配（DDA）来提供快速的临床决策支持。
NGS分析确定了38个基因改变。DDA确定了6个潜在驱动基因、24个靶点和79种MTA。基于支持性分子证据以及该肿瘤类型中已注册疗法中DDA排名最高，选择依维莫司作为一线治疗药物。患者的一般状况和肝功能迅速改善，CT检查显示淋巴结部分缓解，其他部位病情稳定。
通过液体活检、全面分子谱分析和DDA进行精准肿瘤学应用，使得晚期pNET的个性化一线治疗在临床环境中可行。
