NEW YORK – Memorial Sloan Kettering Cancer Center (MSK) is in the process of implementing a new rapid sequencing-based cancer panel to complement ongoing comprehensive genomic profiling (CGP).

纽约——纪念斯隆·凯特琳癌症中心（MSK）正在实施一个新的基于快速测序的癌症小组，以补充正在进行的全面基因组分析（CGP）。

The assay, branded as MSK-React, is based on a new panel from Pillar Biosciences, recently launched as the OncoReveal Nexus. MSK-React masks two of the 21 genes in the panel and is available in separate reported formats for solid and hematological tumors.

该测定法被称为MSK React，它基于Pillar Biosciences的一个新小组，该小组最近作为OncoReveal Nexus推出。MSK React掩盖了面板中21个基因中的两个，并可用于实体瘤和血液肿瘤的单独报告格式。

'It's a bit of a Frankenpanel,' said Mark Ewalt, MSKCC's associate medical director for laboratory operations in diagnostic molecular pathology. 'Rather than make an indication-specific panel, we took all of our requests for rapid analytes, and we consolidated them onto one targeted panel and then designed it around the most frequently mutated regions there so that we could deploy this as a rapid assay for clinical use and trial enrollment.'.

MSKCC负责诊断分子病理学实验室操作的副医学主任马克·伊瓦尔特（MarkEwalt）说，这有点像一个弗兰肯人小组（Frankenpanel）我们没有建立一个特定于适应症的小组，而是将我们所有的快速分析物请求整合到一个目标小组中，然后围绕那里最常见的突变区域进行设计，以便我们可以将其部署为临床使用和试验注册的快速测定。”。

The clinic will also run MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), its large CGP assay, in parallel. 'So anything that's negative upfront on React we'll get more information on, so we can target those patients for earlier-phase clinical trials or feed that information into the research cohorts at MSK.'.

该诊所还将同时运行MSK-IMPACT（可操作癌症靶标的综合突变分析），这是其大型CGP分析。”因此，任何对React有负面影响的信息，我们都会获得更多信息，因此我们可以针对这些患者进行早期临床试验，或者将这些信息输入MSK的研究队列。”。

MSK has had its assay approved for clinical use by the New York State Department of Health and Mental Hygiene and has begun a soft rollout of the panel in place of single-analyte PCR tests.

MSK的检测方法已被纽约州卫生和精神卫生部批准用于临床，并已开始软性推出该小组，以替代单一分析物PCR检测。

Duke University Health and the University of Southern California's Keck School of Medicine are also in the process of adopting the panel and collaborated with Pillar on the assay design, Pillar Chief Marketing Officer Brian Wright said in an email.

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'While our intended use of this assay is multifaceted, our primary aim is to streamline single gene testing — currently performed using several different methodologies — to a single, rapid NGS platform,' Sarah Rapisardo, director of test development at Duke University Health System Clinical Labs, said in an email.

杜克大学卫生系统临床实验室测试开发主任莎拉·拉皮萨多（SarahRapisardo）在一封电子邮件中说：“虽然我们对这种检测方法的预期用途是多方面的，但我们的主要目标是将目前使用几种不同方法进行的单基因检测简化为一个单一的快速NGS平台。”。

'We are seeking rapid results for clinically actionable genes that drive therapy selection, with an initial focus on hematological malignancies. We are increasing workflow efficiencies on a platform with greater scalability, a more rapid turnaround time, and, in many cases, greater sensitivity.'.

“我们正在寻求推动治疗选择的临床可行基因的快速结果，最初的重点是血液系统恶性肿瘤。我们正在一个具有更大可扩展性、更快周转时间以及在许多情况下更高灵敏度的平台上提高工作流效率。”。

Ewalt further noted that balancing the desire for rapid turnaround time with the desire for comprehensive testing 'is a challenge for the field globally.' But what this will cost and who will pay for parallel testing remains to be seen.

Ewalt进一步指出，平衡快速周转时间和全面测试的愿望是全球该领域面临的挑战但这将产生什么样的成本，谁将为并行测试付费，还有待观察。

MSK is a pioneer in the field of sequencing-based tumor profiling, nabbing the first US Food and Drug Administration authorization for such a test in 2017 with MSK-IMPACT. Now available for both solid and hematological tumors, the CGP assays evaluate 505 and 400 genes, respectively, looking for protein-coding mutations, copy number alterations, and other variation in cancer-associated genes that can inform therapy selection..

MSK是基于测序的肿瘤分析领域的先驱，2017年凭借MSK-IMPACT获得了美国食品和药物管理局的首次此类测试授权。CGP分析现在可用于实体瘤和血液肿瘤，分别评估505和400个基因，寻找蛋白质编码突变，拷贝数改变以及癌症相关基因的其他变异，这些变异可以为治疗选择提供信息。。

'Eight to 10 years ago, oncologists wanted the biggest test possible,' Ewalt said. 'Now, there's a little more nuanced approach to this.' CGP is still important, especially for getting a total workup for patients and to contribute to the hospital's research mission. But targeted therapies are now available as frontline treatments and clinicians want genomic information as soon as possible.

“八到十年前，肿瘤学家希望进行尽可能大的测试，”Ewalt说现在，有一种更细微的方法来解决这个问题。”CGP仍然很重要，尤其是对患者进行全面检查并为医院的研究任务做出贡献。但是现在有针对性的治疗可以作为一线治疗，临床医生希望尽快获得基因组信息。

With a turnaround time of as little as three days — compared to about two weeks for CGP — the hope is that this type of assays can help clinicians reduce the time to settling on the optimal treatment for a patient, whether that's targeted therapy or more traditional chemotherapy..

由于周转时间只有三天，而CGP只有两周左右，因此希望这种检测方法可以帮助临床医生减少确定患者最佳治疗的时间，无论是靶向治疗还是更传统的化疗。。

OncoReveal Nexus is a PCR-based targeted panel that analyzes 111 total targets across 21 genes. That includes mutation hotspots in 20 genes and full coverage of TP53 and FLT3 internal tandem duplications. The assay can work with samples from blood or from formalin-fixed, paraffin-embedded samples. Pillar recommends sequencing with at least 615,000 reads.

OncoReveal Nexus是一个基于PCR的靶向小组，可分析21个基因中的111个总靶标。这包括20个基因的突变热点以及TP53和FLT3内部串联重复的完整覆盖。该测定法可以用于血液或福尔马林固定石蜡包埋样品的样品。支柱建议测序至少有615000个读数。

List price for a 24-reaction kit is $5,000, or $208 per sample. .

24反应试剂盒的标价为5000美元，即每个样品208美元。

MSK will primarily run the assay on the Illumina MiSeq instrument, a smaller benchtop platform, with the Micro reagent kit. 'This allows us to batch 13 clinical samples and controls,' Ewalt said. With a 19-hour run time, an 'ideal' three-day workflow sees sequencing data ready by noon on day two and a report by the end of day three.

MSK将主要在Illumina MiSeq仪器（一个较小的台式平台）上使用微量试剂盒进行测定。”伊瓦尔特说，这使我们能够批量处理13个临床样本和对照。运行时间为19小时，“理想的”三天工作流程可以在第二天中午前准备好测序数据，在第三天结束前准备好报告。

Over weekends, when the lab isn't open, they'll plan to batch more samples on a bigger v2 flow cell, which takes about 27 hours, he said..

他说，周末，当实验室不开放时，他们将计划在更大的v2流动池中批量处理更多样品，这需要大约27小时。。

MSK does not yet have any studies set up to evaluate the effects of getting results with a smaller, faster assay. 'For right now, we're still sort of just rolling it out to try to meet the clinical desires.'

MSK还没有建立任何研究来评估用更小更快的检测方法获得结果的效果。”就目前而言，我们仍在尝试推出它，以满足临床需求。”

Duke is not planning to use the assay in parallel with CGP, Rapisardo said. 'We will report a subset of genes in the panel, plus added custom content for clinically relevant pharmacogenomic targets.' They're validating it now with plans to roll it out early next year.

Rapisardo说，杜克大学不打算与CGP同时使用这种检测方法我们将在小组中报告一部分基因，并为临床相关的药物基因组学目标添加自定义内容。”他们现在正在验证它，计划明年初推出。

MSK completed its validation in April and received conditional approval from New York in June. A soft rollout began in late August, replacing single-analyte testing in lung cancer. 'We found this [assay] very robust,' Ewalt said. Pillar recommends an input of 10 ng of DNA; however, input dilution studies suggested 'adequate performance' at 2.5 ng and above, he said.

MSK于4月完成了验证，并于6月获得了纽约的有条件批准。8月下旬开始软性推出，取代肺癌的单一分析物检测。”伊瓦尔特说：“我们发现这种检测方法非常可靠。”。支柱建议输入10 ng DNA；然而，他说，输入稀释研究表明，在2.5 ng及以上时“足够的性能”。

'If it's really desperate and with an attending review, we may go lower,' he said. That's compared to a goal of 250 ng input for MSK-IMPACT and a lower limit of 50 ng. 'We validated on cell-free DNA as well as genomic DNA from a variety of sources, and it works quite well,' he added..

他说，如果真的很绝望，并且有人参加了审查，我们可能会降低价格。相比之下，MSK-IMPACT的目标是250 ng的输入量和50 ng的下限。“我们对来自各种来源的无细胞DNA和基因组DNA进行了验证，效果很好，”他补充道。。

The small panel size makes it fast but precludes the test from analyzing some 'emerging biomarkers' such as tumor mutational burden, Ewalt noted. 'There are going to be intrinsic limitations,' he said.

Ewalt指出，小组规模小，速度快，但无法分析一些“新兴生物标志物”，如肿瘤突变负荷他说，这将有内在的局限性。

How healthcare systems will bill for the test remains unclear. 'We have worked with our billing and revenue office to review coverage based on insurance payors and plans,' Rapisardo said. Ewalt noted that many payors will not cover two sequencing-based tests for the same sample, but did not know whether MSK would eat the costs or pass them on to the patient.

目前尚不清楚医疗保健系统将如何为该测试付费。”Rapisardo说，我们已经与计费和收入办公室合作，根据保险付款人和保险计划审查保险范围。Ewalt指出，许多付款人不会对同一样本进行两次基于测序的测试，但不知道MSK是否会承担费用或将费用转嫁给患者。

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'Clinical guidelines are starting to push for faster and faster turnaround times, and the National Comprehensive Cancer Network and others are starting to recommend results very quickly, but also increasing numbers of biomarkers to get those results,' he said. 'I really hope that payors can find a way to reimburse labs for a rapid assessment that meets the guidelines, as well as continuing to support the reimbursement for comprehensive genome profiling.

我真的希望付款人能够找到一种方法来补偿实验室进行符合指南的快速评估，并继续支持全面基因组分析的报销。

I think there's value in both.'.

我认为两者都有价值。”。