Background Targeted capture sequencing can potentially facilitate precision medicine, but the feasibility of this approach in gastrointestinal (GI) malignancies is unknown. Patients and methods The FOrMAT (Feasibility of a Molecular Characterisation Approach to Treatment) study was a feasibility study enrolling patients with advanced GI malignancies from February 2014 to November 2015. Targeted capture sequencing (mainly using archival formalin-fixed paraffin-embedded diagnostic/resection samples) was carried out to detect mutations, copy number variations and translocations in up to 46 genes which had prognostic/predictive significance or were targets in current/upcoming clinical trials. Results Of the 222 patients recruited, 215 patients (96.8%) had available tissue samples, 125 patients (56.3%) had ≥16 genes successfully sequenced and 136 patients (61.2%) had ≥1 genes successfully sequenced. Sample characteristics influenced the proportion of successfully sequenced samples, e.g. tumour type (colorectal 70.9%, biliary 52.6%, oesophagogastric 50.7%, pancreas 27.3%, P = 0.002), tumour cellularity (high versus low: 78.3% versus 13.3%, P ≤ 0.001), tumour content (high versus low: 78.6% versus 27.3%, P = 0.001) and type of sample (resection versus biopsy: 82.4% versus 47.6%, P ≤ 0.001). Currently, actionable alterations were detected in 90 (40.5%) of the 222 patients recruited (66% of the 136 patients sequenced) and 2 patients subsequently received a targeted therapy. The most frequently detected currently actionable alterations were mutations in KRAS, BRAF, TP53 and PIK3CA. For the 205 patients with archival samples, the median time to obtain sequencing results was 18.9 weeks, including a median of 4.9 weeks for sample retrieval and 5.1 weeks for sequencing. Conclusions Targeted sequencing detected actionable alterations in formalin-fixed paraffin-embedded samples, but tissue characteristics are of critical importance in determining sequencing success. Routine molecular profiling of GI tumours outside of clinical trials is not an effective use of healthcare resources unless more targeted drugs become available. ClinicalTrials.gov identifier NCT02112357.

中文翻译：

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研究胃肠道恶性肿瘤中肿瘤分子谱分析在常规临床实践中的可行性。


背景 靶向捕获测序有可能促进精准医疗，但这种方法在胃肠道 (GI) 恶性肿瘤中的可行性尚不清楚。患者和方法 FORMAT（分子表征治疗方法的可行性）研究是一项可行性研究，招募了 2014 年 2 月至 2015 年 11 月患有晚期胃肠道恶性肿瘤的患者。 靶向捕获测序（主要使用档案福尔马林固定石蜡包埋的诊断/切除样本） ）用于检测多达 46 个基因的突变、拷贝数变异和易位，这些基因具有预后/预测意义或者是当前/即将进行的临床试验的目标。结果 在招募的222名患者中，215名患者（96.8%）有可用的组织样本，125名患者（56.3%）有≥16个基因成功测序，136名患者（61.2%）有≥1个基因成功测序。样本特征影响成功测序样本的比例，例如肿瘤类型（结直肠癌70.9％，胆道癌52.6％，食管胃癌50.7％，胰腺癌27.3％，P = 0.002），肿瘤细胞结构（高与低：78.3％与13.3％，P≤ 0.001）、肿瘤含量（高与低：78.6% 与 27.3%，P = 0.001）和样本类型（切除与活检：82.4% 与 47.6%，P ≤ 0.001）。目前，在招募的 222 名患者中，有 90 名 (40.5%) 检测到了可采取行动的改变（136 名测序患者中的 66%），并且 2 名患者随后接受了靶向治疗。目前最常检测到的可操作的改变是 KRAS、BRAF、TP53 和 PIK3CA 的突变。对于205名存档样本的患者，获得测序结果的中位时间为18.9周，其中样本检索的中位时间为4.9周，测序的中位时间为5.1周。 结论 靶向测序检测到福尔马林固定石蜡包埋样品中可操作的改变，但组织特征对于确定测序成功至关重要。除非有更多的靶向药物可用，否则临床试验之外的胃肠道肿瘤的常规分子分析并不能有效利用医疗资源。 ClinicalTrials.gov 标识符 NCT02112357。