Goranova T, Ennis D, Piskorz A M, Macintyre G, Lewsley L A, Stobo J, Wilson C, Kay D, Glasspool R M, Lockley M, Brockbank E, Montes A, Walther A, Sundar S, Edmondson R, Hall G D, Clamp A, Gourley C, Hall M, Fotopoulou C, Gabra H, Freeman S, Moore L, Jimenez-Linan M, Paul J, Brenton J D, McNeish I A
Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK.
Institute of Cancer Sciences, University of Glasgow, G61 1QH, UK.
Br J Cancer. 2017 May 9;116(10):1294-1301. doi: 10.1038/bjc.2017.86. Epub 2017 Mar 30.
Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC).
Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA.
We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 μg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients.
Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.
研究肿瘤演变和获得性化疗耐药性需要对连续的肿瘤组织进行分析。我们描述了在复发性卵巢高级别浆液性癌（HGSC）患者中获取研究性活检组织的可行性。
复发性卵巢HGSC患者在二次减瘤手术期间接受了影像引导活检或术中活检，样本用基于甲醇的固定剂固定。对活检DNA进行标记扩增子测序。
我们筛查了519例患者以纳入220例。202例患者活检成功，其中118例为影像引导活检。影像引导活检中有22例与研究相关的不良事件（AE），均为1级和2级；疼痛是最常见的AE。118例活检中有3例（2.5%）出现预先指定的严重AE。87%的活检组织适合用于基因组分析。DNA产量中位数为2.87μg，与18G针相比，使用14G或16G针的活检组织DNA产量更高。94.4%的患者检测到TP53突变。
在复发性HGSC患者中获取肿瘤活检组织用于研究是安全可行的。不良事件罕见。绝大多数活检组织产生的DNA足以进行基因组分析——我们建议在此类活检中使用更大规格的针和甲醇固定，因为DNA产量更高且不良事件没有增加。
