“NIPT教父”卢煜明在鼻咽癌检测方面的进展登上《新英格兰医学杂志》
2017/08/11
由于ctDNA在血液中实在太罕见,香港中文大学的卢煜明(Dennis Lo)教授将目标转到会引起鼻咽癌的Epstein-Barr的DNA上,在鼻咽癌筛查中进行尝试,提高了该疾病的早期检测和生存率。他领导的这项研究,8月10日发表在《新英格兰医学杂志》NEJM上。


科学家在液态活检有助于筛查癌症患者方面有了第一个重要证据。很多这样的研究都在努力检测和分析“循环肿瘤DNA”(ctDNA),许多公司正在努力开发这些用于筛选的版本,如乳房X光检查、结肠镜检查等可能的替代方案。但ctDNA在血液中实在是太罕见了。于是香港的研究人员将目标转到会引起鼻咽癌的Epstein-Barr的DNA上,在鼻咽癌筛查中进行尝试,提高了该疾病的早期检测和生存率。新的研究表明,此方法至少对于这种在当地普遍存在的癌症是有效的。

这是由于每个鼻咽癌肿瘤细胞带有50个拷贝的Epstein-Barr基因组,研究人员的目标序列在每个病毒基因组发生约10次扩增。这意味着在每个肿瘤细胞中,靶目标是人DNA的500倍。

香港中文大学的卢煜明(Dennis Lo)教授说:“这项工作在更大范围内是非常令人兴奋的,因为它提供了一个测试其它肿瘤类型,如肺或乳腺的蓝图。”他领导的这项研究,8月10日发表在《新英格兰医学杂志》NEJM上。卢煜明教授最著名的发现是在母亲的血液中发现胎儿DNA,这为孕妇提供了一个无创检测的新时代。

对2万人的筛查让确认的34人大都活过3年

这项研究涉及鼻咽癌,它形成于鼻子后面的喉咙顶部。这是一个很好的DNA筛查试验案例,因为它是一种侵袭性癌症,早期发现非常重要,在癌症最常见的中年男性人群中可以进行筛查。而且,Epstein-Barr病毒在大多数情况下都存在,所以试验可以寻找从肿瘤进入血液大量的病毒DNA,而不是癌细胞本身。


该项筛查的大致情况

在约20000名进行筛选的男性中,1112人或5.5%人发现了病毒DNA。其中309人在一个月后进行了验证性试验。内窥镜检查和核磁共振检查后,确认34人得了癌症。34种癌症中有16例是非常早期的,这种癌症在早期阶段不会有任何症状。三年后,除了一个病人外,所有的病人都活了下来,在接受标准放疗后没有癌症的迹象。相比之下,通常只有70%的鼻咽癌患者能存活至少一段时间。

在鼻咽癌早期的阶段中该检测有效提高生存率

在鼻咽癌早期的阶段里发现更多的案例:鼻咽癌I期和II期阶段发现71 %的样本存在病毒DNA,在过去五年曾做过的鼻咽癌治疗的对照组中只有20%。这是很重要的,因为早期的病例通常仅用放射治疗,但晚期的患者需要化疗,而治疗则不那么成功。

筛选似乎也提高了3年疾病不恶化的生存率(3-year progression-free survival)为97%,对照组的话是70%。只有一个筛查阴性的人在一年内患上了鼻咽癌。


鼻咽癌阶段的分布和生存率的变化

研究人员估计,确定一个癌症病例需要对593人进行筛查,总费用为28600美元。在香港是值得的。鼻咽癌在华南比较常见,每10万人中多达35例。但在其它该疾病罕见的地方,就会需要对更多的人进行筛选,在找到每个癌症病例的费用就更大。美国约翰霍普金斯医学院的Richard Ambinder博士,给杂志写了一个评论。他说:“尽管如此,这表明液体活检有很大的希望。这是一项确实能挽救生命的进步。”

参考资料

Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer

Study boosts hope of 'liquid biopsies' for cancer screening

Can a ‘liquid biopsy’ detect cancer and save lives?

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  • Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer

    BACKGROUND Circulating cell-free Epstein–Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. METHODS We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI). RESULTS A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively. CONCLUSIONS Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort.

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