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Abstract：
OBJECTIVE: In patients with oligometastatic non-small-cell lung cancer (NSCLC), systemic therapy in combination with local ablative treatment of the primary tumour and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary NSCLC and corresponding brain metastases (BM).
METHODS: We retrospectively identified patients with oligometastatic NSCLC and synchronous (<3 months) or metachronous (>3 months) BM who underwent surgical resection of both primary tumour and BM. Mutation profiling of formalin-fixed paraffin-embedded tumour cell blocks was performed by targeted next-generation sequencing using the Oncomine Focus Assay panel.
RESULTS: Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumours (67.4%) and 40 BM (86.9%). The alteration of the primary tumours was preserved in the corresponding BM in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumours and BM was a KRAS (Kirsten rat sarcoma viral oncogene) mutation (s = 21). In 16 patients (34.8%), the BM harboured additional oncogenic alterations. The presence of a private genetic alteration in the BM was an independent predictor of shorter overall survival.
CONCLUSIONS: In oligometastatic NSCLC, BM retain the main genetic alterations of the primary tumours. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the BM are dismal.
METHODS: We retrospectively identified patients with oligometastatic NSCLC and synchronous (<3 months) or metachronous (>3 months) BM who underwent surgical resection of both primary tumour and BM. Mutation profiling of formalin-fixed paraffin-embedded tumour cell blocks was performed by targeted next-generation sequencing using the Oncomine Focus Assay panel.
RESULTS: Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumours (67.4%) and 40 BM (86.9%). The alteration of the primary tumours was preserved in the corresponding BM in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumours and BM was a KRAS (Kirsten rat sarcoma viral oncogene) mutation (s = 21). In 16 patients (34.8%), the BM harboured additional oncogenic alterations. The presence of a private genetic alteration in the BM was an independent predictor of shorter overall survival.
CONCLUSIONS: In oligometastatic NSCLC, BM retain the main genetic alterations of the primary tumours. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the BM are dismal.
摘要：
目的：在寡转移型非小细胞肺癌患者中，全身治疗与原发性肿瘤和所有转移部位的局部消融治疗相结合，可改善预后。对于患者选择和治疗分配，进一步了解寡转移态的分子特征是必要的。这里,我们对原发性非小细胞肺癌和相应的脑转移进行了基因鉴定.
方法：我们回顾性分析了患有寡转移型非小细胞肺癌和同步（<3个月）或异时性（>3个月）脑转移的患者，这些患者同时接受了原发肿瘤和脑转移的手术切除。福尔马林固定的石蜡包埋的肿瘤细胞块的突变分析通过靶向下一代测序使用oncomine焦点测定面板进行。
结果：在46个配对样品中成功测序。在31个原发性肿瘤（67.4％）和40个脑转移瘤（86.9％）中存在致癌改变。31例中有29例（93.5％）保留了相应的脑转移瘤中原发肿瘤的改变。在原发性肿瘤和脑转移中最普遍的致癌驱动因素是KRAS突变(n=21)。16例患者（34.8%），脑转移有额外的致癌改变。脑转移中私人遗传改变的存在是总生存期较短的独立预测因素。
结论：在寡转移非小细胞肺癌中，脑转移保留了原发性肿瘤的主要遗传改变。患者可能受益于突变的KRAS的靶向抑制。脑转移瘤中的其他私人遗传改变令人沮丧。
方法：我们回顾性分析了患有寡转移型非小细胞肺癌和同步（<3个月）或异时性（>3个月）脑转移的患者，这些患者同时接受了原发肿瘤和脑转移的手术切除。福尔马林固定的石蜡包埋的肿瘤细胞块的突变分析通过靶向下一代测序使用oncomine焦点测定面板进行。
结果：在46个配对样品中成功测序。在31个原发性肿瘤（67.4％）和40个脑转移瘤（86.9％）中存在致癌改变。31例中有29例（93.5％）保留了相应的脑转移瘤中原发肿瘤的改变。在原发性肿瘤和脑转移中最普遍的致癌驱动因素是KRAS突变(n=21)。16例患者（34.8%），脑转移有额外的致癌改变。脑转移中私人遗传改变的存在是总生存期较短的独立预测因素。
结论：在寡转移非小细胞肺癌中，脑转移保留了原发性肿瘤的主要遗传改变。患者可能受益于突变的KRAS的靶向抑制。脑转移瘤中的其他私人遗传改变令人沮丧。
