The European Society for Medical Oncology defines rare cancers as 5 or fewer cases per 100,000 persons per year. For many rare cancers, no standard of care exists, and treatment is often extrapolated. Identifying potentially targetable genomic alterations in rare tumors is a rational approach to improving treatment options. We sought to catalog these mutations in rare tumors and to assess their clinical utility. For this retrospective analysis, we selected rare tumor patients from a dataset of patients who underwent clinical tumor genomic profiling. Sarcomas were excluded. To index potentially actionable alterations, patients' reports were reviewed for mutations in cancer-associated genes and pathways. Respective clinical records were abstracted to appraise the benefit of using a targeted therapy approach. Actionable alterations were defined as targeted by a drug available on-label, off-label, or in clinical trials. The 95 patients analyzed had 40 different tumor subtypes, most common being adenoid cystic (13%), cholangiocarcinoma (7%), and metaplastic breast (6%). At least one genomic alteration was identified in 87 patients (92%). The most common identifiable mutations were in TP53 (23%), KRAS (10%), PIK3CA (9%), CDKN2A/B (8%), BRAF (7%), MLL (7%), and ARID1A (6%). Thirty-six patients (38%) with 21 different tumors had at least one potentially actionable alteration. Thirteen patients received targeted therapy. Of these, 4 had a partial response, 6 had stable disease, and 3 had progressive disease as the best response. The addition of genomic profiling to management of rare cancers adds a potential line of therapy for cancers that have little or no standard of care. In our analysis, tumors with a BRAF alteration responded well to BRAF inhibitors. Mol Cancer Ther; 17(7); 1595–601. ©2018 AACR.

中文翻译：

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用于罕见癌症精准肿瘤学的临床下一代测序

欧洲肿瘤内科学会将罕见癌症定义为每年每 100,000 人中 5 个或更少的病例。对于许多罕见的癌症，不存在治疗标准，治疗通常是外推的。识别罕见肿瘤中潜在的可靶向基因组改变是改善治疗选择的合理方法。我们试图对罕见肿瘤中的这些突变进行分类并评估它们的临床效用。对于这项回顾性分析，我们从接受临床肿瘤基因组分析的患者数据集中选择了罕见的肿瘤患者。肉瘤被排除在外。为了索引可能可行的改变，对患者报告中的癌症相关基因和通路的突变进行了审查。提取了各自的临床记录以评估使用靶向治疗方法的益处。可操作的改变被定义为以标签上、标签外或临床试验中可用的药物为目标。分析的 95 名患者有 40 种不同的肿瘤亚型，最常见的是腺样囊性 (13%)、胆管癌 (7%) 和化生性乳腺 (6%)。在 87 名患者 (92%) 中发现了至少一种基因组改变。最常见的可识别突变是 TP53 (23%)、KRAS (10%)、PIK3CA (9%)、CDKN2A/B (8%)、BRAF (7%)、MLL (7%) 和 ARID1A (6%) ）。有 21 种不同肿瘤的 36 名患者 (38%) 至少有一个潜在的可操作改变。13 名患者接受了靶向治疗。其中，4 例部分缓解，6 例疾病稳定，3 例疾病进展为最佳反应。将基因组分析添加到罕见癌症的管理中，为几乎没有或没有标准护理的癌症增加了一条潜在的治疗方法。在我们的分析中，具有 BRAF 改变的肿瘤对 BRAF 抑制剂反应良好。摩尔癌症治疗; 17(7); 1595-601。©2018 AACR。