NEW YORK – New research presented this week at the annual meeting of the American Society for Clinical Oncology showcased some early efforts to use liquid biopsy testing to adapt cancer treatment in real time, in this case in patients with head and neck tumors.

纽约——本周在美国临床肿瘤学会年会上展示的新研究介绍了一些早期尝试，这些尝试利用液体活检测试来实时调整治疗方案，针对的是头颈肿瘤患者。

Introducing the topic during a session, University of Michigan oncologist Paul Swiecicki said that it's an exciting moment for the field of head and neck cancer treatment, and it's 'getting better all the time.'

在一次会议中介绍该主题时，密歇根大学的肿瘤学家保罗·斯维奇基表示，头颈癌治疗领域正处于一个激动人心的时刻，并且“一直在不断进步”。

The early data emerging suggests that personalized care may decrease treatment-related toxicity while simultaneously optimizing survival outcomes, but he cautioned that advancement to the clinic rests on appropriately designed clinical utility trials and developing a better understanding of the concordance between different biomarkers.

早期数据显示，个性化护理可能在降低治疗相关毒性的同时优化生存结果，但他提醒说，进入临床阶段需要依赖合理设计的临床效用试验，并更好地理解不同生物标志物之间的一致性。

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Glenn Hanna, a clinical researcher at the Dana-Farber Cancer Institute, shared results from a Phase II study in which he and his colleagues trialed a strategy to de-intensify chemoradiation treatment in HPV-positive oropharyngeal cancer (OPC) patients whose pre-therapy ctDNA levels dropped at least 95 percent after the start of treatment..

达纳-法伯癌症研究所的临床研究员格伦·汉纳分享了一项二期研究的结果，在该研究中，他和他的同事试验了一种降低化疗强度的策略，针对的是人乳头瘤病毒阳性口咽癌患者，这些患者在治疗开始后，治疗前的循环肿瘤DNA水平至少下降了95%。

According to Hanna, HPV-positive OPC patients can have good outcomes when treated with

根据汉娜的说法，HPV阳性的OPC患者在治疗时可以获得良好的结果

concurrent platinum-based chemo and radiation, but the long-term toxicity can be significant. Investigators have tried strategies to de-intensify treatment to mitigate adverse effects, but they are the first to do so using liquid biopsy testing to detect tumor-associated viral DNA.

同时进行铂类化疗和放疗，但长期毒性可能相当显著。研究人员尝试了减轻治疗强度的策略以缓解不良反应，但他们却是首个使用液体活检测试来检测肿瘤相关病毒DNA的人。

The trial enrolled patients into two cohorts based on clinical risk factors and detectable circulating tumor-HPV DNA using Naveris' NavDx assay. One cohort, the low-risk arm, included individuals with lower-grade disease and a smoking history of less than 10 packs per year who received a de-intensified chemoradiation regimen.

该试验根据临床风险因素和使用Naveris的NavDx检测方法可检测到的循环肿瘤HPV DNA，将患者分为两个队列。其中一个队列为低风险组，包括低级别疾病且吸烟史少于每年10包的个体，他们接受了减量的放化疗方案。

The other arm, deemed intermediate risk, included patients with higher grade tumors or a longer smoking history, and a pre-treatment HPV DNA score of greater than 200, who were started on a standard, more aggressive treatment strategy..

另一组为中等风险组，包括患有更高级别肿瘤或有较长吸烟史且治疗前 HPV DNA 评分大于 200 的患者，这些患者开始接受标准化、更强效的治疗策略。

Overall, 27 patients were assigned to the intermediate-risk arm with a median pre-treatment HPV DNA of 2,346. Among this group, 18 saw greater than 95 percent DNA clearance on initial therapy and were de-escalated. At a median follow-up of 14 months, the two-year progression-free survival estimate was 92 percent across the de-escalated and low-risk patients combined..

总体而言，27名患者被分配到中风险组，治疗前HPV DNA的中位数为2,346。在这一组中，18名患者的初始治疗使其DNA清除率超过95％，并进行了降级治疗。在中位随访14个月时，降级治疗和低风险患者合并后的两年无进展生存率估计为92％。

Only five patients recurred as of the study cutoff. Two were in the initial low-risk group, and three were in the de-escalated group, Hanna said. As of a more recent analysis, there has been an additional recurrence in the standard-of-care arm, he added. Looking at the biology of these particular patients, 'nothing jumped out in particular' to indicate why lower-intensity treatment wasn't as well received as in the rest of the cohort..

截至研究截止日期，只有五名患者复发。汉纳说，其中两名患者属于最初的低风险组，三名患者属于降级组。他补充说，根据最近的分析，在标准治疗组中又出现了一例复发。观察这些特定患者的生物学特征，“没有什么特别突出的”能表明为什么较低强度的治疗在这一组中不如在其他组中效果好。

In a second presentation, investigators from China's Sun Yat-sen University Cancer Center reported on another trial, this time focused on escalating treatment based on ctDNA dynamics.

在第二次报告中，中国中山大学癌症中心的研究人员报告了另一项试验，这次试验的重点是根据ctDNA动态调整治疗方案。

Also a Phase II trial, the team's study used targeted circulating DNA associated with a different pathogen-linked cancer, in this case, Epstein-Barr virus-positive nasopharyngeal carcinoma.

此外，在二期试验中，该团队的研究使用了与另一种病原体相关癌症有关的靶向循环DNA，在这种情况下，是与Epstein-Barr病毒相关的鼻咽癌。

Investigators recruited a total of 142 locoregionally advanced NPC patients with detectable pretreatment EBV DNA, treating them with gemcitabine plus cisplatin induction chemotherapy and monitoring them longitudinally for circulating biomarker levels.

研究人员招募了总共142名局部晚期鼻咽癌患者，这些患者在治疗前可检测到EBV DNA，使用吉西他滨联合顺铂诱导化疗进行治疗，并纵向监测其循环生物标志物水平。

Based on their results, patients were classified as low or at-risk. The low-risk group continued standard therapy while the at-risk group started treatment intensification — with the addition of adjuvant metronomic capecitabine for intermediate-risk patients and the addition of 12 cycles of sintilimab for the high-risk group..

基于他们的结果，患者被分为低危或高危。低危组继续标准治疗，而高危组开始强化治疗——中危患者加用辅助性节律性卡培他滨，高危组加用12个周期的信迪利单抗。

According to the authors, their primary endpoint of treatment failure-free survival was met, with three-year FFS of 89 percent in the adaptive therapy population. The results compared favorably with historic data in similar populations who did not undergo adaptive therapy, and toxicity was manageable..

根据作者的说法，他们达到了无治疗失败生存的主要终点，适应性治疗人群的三年无失败生存率为89%。结果与未接受适应性治疗的相似人群的历史数据相比有利，且毒性可控。

Hanna said during a discussion of the results that he and his colleagues are also interested in and are starting to work with the idea of intensification.

汉纳在讨论结果时表示，他和他的同事也对强化这个概念感兴趣，并开始围绕这个概念展开工作。

'I'm very interested in the question of whether we can take higher-risk patients after treatment who are still MRD or ctDNA positive and appropriately randomize them or treat them with intensification, which would be adjuvant therapy, so we've started to work on that,' he said.

“我对我们能否在治疗后对仍然MRD或ctDNA阳性的高风险患者进行适当随机分组或强化治疗，即辅助治疗，非常感兴趣，所以我们已经开始就此展开工作，”他说。

Other goals include trying to find ways to tailor treatment for the lower-risk patients, whose ctDNA kinetics didn't seem to indicate a path for adaptive treatment.

其他目标包括试图找到针对低风险患者量身定制治疗方案的方法，这些患者的ctDNA动力学似乎并未显示出适应性治疗的路径。

'I think we have some work to do to figure out what the right cutoffs are or how we should treat those patients. But that being said, I do believe that in several years, we will, with everyone's help and the use of these assays in these sorts of prospective, well-designed trials, get to a point where we can start using this to make decisions,' Hanna said..

“我认为我们需要做一些工作来确定正确的临界值是什么，或者我们应该如何对待那些患者。话虽如此，我确实相信，再过几年，通过大家的帮助以及在这些前瞻性的、精心设计的试验中使用这些检测方法，我们能够到达一个可以开始利用这些信息来做决策的阶段，”汉娜说。

Hanna also said that his team has begun to explore ctDNA test technologies beyond the Naveris platform, including methylation-based and tumor-informed personalized MRD assays.

汉娜还表示，他的团队已开始探索 Naveris 平台之外的 ctDNA 检测技术，包括基于甲基化和肿瘤知情的个性化 MRD 检测。

'I can say, in summary, they look very good. I recognize the issue with them reaching the rest of the world. We're very lucky in the United States to be able to use many of these assays … and not necessarily have patient billing, although that's not a perfect situation,' he said.

“我总结一下，它们看起来非常好。我认识到它们在进入世界其他地区时存在的问题。在美国，我们非常幸运能够使用许多这样的检测方法……而且不一定会对患者收费，尽管这不是一个完美的情况，”他说。

Swiecicki cautioned that p

斯维克茨基警告说 p

ivotal questions still need to be answered, including how investigators define molecular response. 'So far, we've just been looking at clearance, but we need in the future to look at mean variant allele frequency and variant allele frequency over time.'

关键问题仍然需要解答，包括调查人员如何定义分子反应。“到目前为止，我们只是在关注清除率，但未来我们需要观察平均变异等位基因频率以及随时间变化的变异等位基因频率。”

Finally, the medical community cannot forget surveillance, he added. 'For many of our patients, biomarker monitoring can facilitate remote surveillance and improve access to care for vulnerable patient populations.'

最后，医学界不能忘记监测，他补充说。‘对于许多患者，生物标志物监测可以促进远程监控，并改善弱势患者群体获得护理的机会。’