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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在常规临床实践中研究在胃肠道恶性肿瘤中进行肿瘤分子谱分析的可行性。

背景技术有针对性的捕获测序可能会促进精密医学的发展，但是这种方法在胃肠道（GI）恶性肿瘤中的可行性尚不明确。患者和方法FOrMAT（治疗的分子表征方法的可行性）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GI恶性肿瘤的患者。有针对性的捕获测序（主要使用福尔马林档案固定的石蜡包埋的诊断/切除样本） ）进行了检测，以检测多达46个具有预后/预测意义或作为当前/即将进行的临床试验目标的基因的突变，拷贝数变异和易位。结果在222名患者中，有215名患者（96.8％）有可用的组织样本，有125名患者（56。3％的患者成功测序了≥16个基因，136例（61.2％）的患者成功测序了≥1个基因。样品特性影响成功测序的样品的比例，例如肿瘤类型（结肠直肠癌70.9％，胆道52.6％，食管胃癌50.7％，胰腺27.3％，P = 0.002），肿瘤细胞（高与低：78.3％对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，在新招募的222例患者中有90例（40.5％）被检测出可操作的改变（在136例患者中占66％），随后有2例患者接受了靶向治疗。目前最常检测到的可操作改变是KRAS，BRAF，TP53和PIK3CA中的突变。对于205名具有存档样本的患者，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。结论靶向测序在福尔马林固定石蜡包埋的样品中检测到可操作的变化，但组织特征对于确定测序成功至关重要。除非有更多靶向药物可供使用，否则在临床试验之外对胃肠道肿瘤进行常规分子谱分析不能有效地利用医疗保健资源。ClinicalTrials.gov标识符NCT02112357。但是组织特征对于确定测序成功至关重要。除非有更多靶向药物可供使用，否则在临床试验之外对胃肠道肿瘤进行常规分子谱分析不能有效地利用医疗保健资源。ClinicalTrials.gov标识符NCT02112357。但是组织特征对于确定测序成功至关重要。除非有更多靶向药物可供使用，否则在临床试验之外对胃肠道肿瘤进行常规分子谱分析不能有效地利用医疗保健资源。ClinicalTrials.gov标识符NCT02112357。