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下一代测序在卡介苗治疗的高危膀胱癌中的应用价值

Interest of next-generation sequencing in BCG-treated high-risk bladder cancer.

作者信息

Jungels C, Martinez Chanza N, Albisinni S, Mercier M, d'Haene N, Rorive S, Roumeguère T

机构信息

Department of urology, Erasme hospital, université Libre-de-Bruxelles, Brussels, Belgium.

Department of oncology, Erasme hospital, université Libre-de-Bruxelles, Brussels, Belgium.

出版信息

Prog Urol. 2018 May;28(6):344-350. doi: 10.1016/j.purol.2018.03.008. Epub 2018 Apr 17.

Abstract

OBJECTIVES

There are only few predictive factors for response of non-musculo-invasive bladder cancer (NMIBC) to Bacillus Calmette-Guérin (BCG) therapy. Our study analyzed the results of the sequencing of new generation (NGS) targeted on 50 genes of oncological interest obtained on bladder resection parts in high-risk NMIBC patients treated with BCG, to describe this population from a molecular point of view and try to correlate these results in patients who present or not recurrence after BCG.

METHODS

We reviewed 63 patients with high grade NMIBC treated between 2014 and 2016 with BCG after endoscopic resection. Each one had NGS analysis. Association tests between mutations detected by NGS and recurrence or progression were realized.

RESULTS

The 45 remaining patients were fully analysed. For 73% of cases a mutation has been found, most frequent one's being FGFR3, TP53 and PIK3CA. With a median follow-up of 24 months (4-40), recurrence was present in 15 patients (33.3%), with 10 NMIBC (22.2%) and 5 progressions to muscular-invasive cancer (11.1%). If some mutations were more frequent in different prognostic groups no significant association has been found. No patient presenting CIS had FGFR3 mutation (P<0.0001).

CONCLUSION

Next generation sequencing in NMIBC could be a supplementary aid in treatment decision making in the future. In an area where personalized medicine is rapidly growing in importance we need larger studies to define molecular characteristics in tumours to detect genomic associations between clinical phenotypes and recurrence or progression of the disease.

LEVEL OF EVIDENCE

摘要

目的

非肌层浸润性膀胱癌(NMIBC)对卡介苗(BCG)治疗反应的预测因素很少。我们的研究分析了对接受BCG治疗的高危NMIBC患者膀胱切除部分进行的针对50个肿瘤相关基因的新一代测序(NGS)结果,从分子角度描述这一人群,并试图将这些结果与BCG治疗后出现或未出现复发的患者相关联。

方法

我们回顾了2014年至2016年间接受内镜切除后用BCG治疗的63例高级别NMIBC患者。每例患者均进行了NGS分析。对NGS检测到的突变与复发或进展之间进行了关联测试。

结果

对剩余的45例患者进行了全面分析。73%的病例发现了突变,最常见的是FGFR3、TP53和PIK3CA。中位随访24个月(4 - 40个月),15例患者(33.3%)出现复发,其中10例为NMIBC(22.2%),5例进展为肌层浸润性癌(11.1%)。尽管某些突变在不同预后组中更常见,但未发现显著关联。没有原位癌(CIS)患者有FGFR3突变(P<0.0001)。

结论

NMIBC中的新一代测序未来可能在治疗决策中起到辅助作用。在个性化医疗重要性迅速增长的领域,我们需要更大规模的研究来确定肿瘤的分子特征,以检测临床表型与疾病复发或进展之间的基因组关联。

证据水平

3级。

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