靶向下一代测序(tNGS)越来越多地用于肿瘤学的治疗决策,但尚未广泛用于前列腺癌。这项研究的目的是确定tNGS用于前列腺癌治疗的当前临床实用性。
七位学术泌尿生殖系统医学肿瘤学家招募并同意前列腺癌患者,主要具有异常的临床和/或病理特征,从2013年到2015年。UW-OncoPlex在福尔马林固定的情况下进行,石蜡包埋(FFPE)原发性肿瘤和/或转移性活检。在与患者沟通之前,在多学科精密肿瘤委员会上讨论了结果。提取FFPE肿瘤DNA用于194个癌症相关基因的tNGS分析。Results,多学科讨论,并记录治疗变化。
45名患者同意,42名患者有可报告的结果。研究结果包括在前列腺癌中经常观察到的基因突变。我们还发现了靶向治疗可用的基因和/或临床试验中的变化。4/42(10%)例,治疗的改变直接源于tNGS和多学科讨论。在30/42(71%)的案例中,有其他选择可用,但没有追求和/或未决。值得注意的是,10/42(24%)的患者在中度或高外显率癌症风险基因中存在可疑的种系突变,包括BRCA2,TP53,ATM,CHEK21例患者的肿瘤有双等位基因MSH6突变和微卫星不稳定。总的来说,34/42(81%)例导致了一定程度的治疗可操作性。局限性包括小尺寸和有限的临床结果。
靶向NGS肿瘤测序可能有助于指导前列腺癌男性的近期和未来治疗选择。一个相当大的子集在癌症易感性基因中具有种系突变,对男性及其亲属具有潜在的临床管理意义。前列腺76:1303-1311,2016。©2016威利期刊,Inc.
Targeted next generation sequencing (tNGS) is increasingly used in oncology for therapeutic decision-making, but is not yet widely used for prostate cancer. The objective of this
study was to determine current clinical utility of tNGS for prostate cancer management.
Seven academic genitourinary medical oncologists recruited and consented patients with prostate cancer, largely with unusual clinical and/or pathologic features, from 2013 to 2015. UW-OncoPlex was performed on formalin-fixed, paraffin-embedded (FFPE) primary tumors and/or metastatic biopsies. Results were discussed at a multidisciplinary precision tumor board prior to communicating to patients. FFPE tumor DNA was extracted for tNGS analysis of 194 cancer-associated genes. Results, multidisciplinary discussion, and treatment changes were recorded.
Forty-five patients consented and 42 had reportable results. Findings included mutations in genes frequently observed in prostate cancer. We also found alterations in genes where targeted treatments were available and/or in clinical trials. 4/42 (10%) cases, change in treatment directly resulted from tNGS and multidisciplinary discussion. In 30/42 (71%) cases additional options were available but not pursued and/or were pending. Notably, 10/42 (24%) of patients harbored suspected germline mutations in moderate or high-penetrance cancer risk genes, including BRCA2, TP53, ATM, and CHEK2. One patient\'s tumor had bi-allelic MSH6 mutation and microsatellite instability. In total, 34/42 (81%) cases resulted in some measure of treatment actionability. Limitations include small size and limited clinical outcomes.
Targeted NGS tumor sequencing may help guide immediate and future treatment options for men with prostate cancer. A substantial subset had germline mutations in cancer predisposition genes with potential clinical management implications for men and their relatives. Prostate 76:1303-1311, 2016. © 2016 Wiley Periodicals, Inc.