K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
JCO Precis Oncol. 2023 Feb;7:e2200336. doi: 10.1200/PO.22.00336.
Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are rare and have a poor prognosis. Most GEP-NEC are diagnosed with metastatic disease, with only minor biopsies available for molecular diagnostics. We assessed the applicability of liquid biopsies for molecular profiling of GEP-NEC.
We performed massive parallel sequencing of 76 cancer-related genes in circulating tumor DNA from 50 patients with advanced GEP-NEC and compared findings to previous analyses of solid tumor biopsies from the same patients. Plasma samples were collected before therapy, and the median time span between blood and tissue sampling was 25 days.
We detected 178 somatic mutations in the liquid biopsies, 127 (71%) were also detected in the solid biopsies, whereas 51 (29%) were unique to the liquid biopsies. In the same 76 genes, we previously detected 199 somatic mutations (single nucleotide variants) in solid biopsies, of which 127 (64%) were also now detected in liquid biopsies. In exploratory subgroup assessments, concordance was higher in patients with liver metastases ( = 1.5 × 10) and increasing with level of liver involvement ( = 1.2 × 10). The concordance was similar between GEP-NEC with different primary sites, except being lower in esophageal cases ( = .001). Concordance was not associated with tumor mutation burden. Tumor tissue mutations also detected in liquid biopsies was lower for MSI (40%) versus MSS tumors (70%; = 7.8 × 10). We identified potentially targetable mutations in plasma of 26 (52%) of patients with GEP-NEC; nine patients (18%) had potentially targetable mutation detected only in liquid biopsies.
Liquid biopsy analyses may be an applicable alternative to solid biopsies in GEP-NEC. Liquid biopsies may add additional mutations compared with tumor biopsies alone and could be useful for biomarker assessment in clinical trials for these patients.
胃肠胰神经内分泌癌（GEP-NEC）较为罕见，预后较差。大多数 GEP-NEC 被诊断为转移性疾病，只有少量活检可用于分子诊断。我们评估了液体活检在 GEP-NEC 分子谱分析中的适用性。
我们对 50 例晚期 GEP-NEC 患者的循环肿瘤 DNA 进行了 76 个与癌症相关基因的大规模平行测序，并将结果与同一患者的实体肿瘤活检的先前分析进行了比较。在治疗前采集血浆样本，血液和组织采样之间的中位时间间隔为 25 天。
我们在液体活检中检测到 178 个体细胞突变，其中 127 个（71%）也在实体活检中检测到，而 51 个（29%）仅在液体活检中检测到。在相同的 76 个基因中，我们之前在实体活检中检测到 199 个体细胞突变（单核苷酸变异），其中 127 个（64%）现在也在液体活检中检测到。在探索性亚组评估中，在有肝转移的患者中，一致性更高（ = 1.5 × 10），并且随着肝受累程度的增加而增加（ = 1.2 × 10）。在不同原发部位的 GEP-NEC 中，一致性相似，但食管病例的一致性较低（ =.001）。一致性与肿瘤突变负担无关。液体活检中还检测到 MSI（40%）肿瘤组织突变低于 MSS 肿瘤（70%； = 7.8 × 10）。我们在 26 例 GEP-NEC 患者的血浆中发现了潜在可靶向的突变（52%）；9 例患者（18%）仅在液体活检中检测到潜在可靶向的突变。
液体活检分析可能是 GEP-NEC 中替代实体活检的一种可行方法。与单独的肿瘤活检相比，液体活检可能会增加额外的突变，并且对于这些患者的临床试验中的生物标志物评估可能有用。
