NEW YORK – Results from a study published last week in JCO Precision Oncology have added to the growing evidence for the value of paired tumor origin testing and molecular profiling to guide the treatment of patients with cancers of unknown primary (CUP).

纽约——上周在JCO Precision Oncology上发表的一项研究结果为成对肿瘤起源检测和分子谱分析在指导原发性未知癌症（CUP）患者治疗中的价值提供了越来越多的证据。

Cancer of unknown primary presents as metastatic disease without a clinically identified primary site. CUP has been associated with especially poor outcomes, at least historically, because patients were limited to physicians' best guess at treatment with empiric chemotherapy.

。至少在历史上，CUP与特别差的结果相关，因为患者仅限于医生对经验性化疗治疗的最佳猜测。

Early studies of tumor origin testing failed to show a benefit, but those trials were conducted without the ability to direct patients to targeted therapy, before the advent of immunotherapy, and with other limitations, such as an overrepresentation of tumor types with no good treatments, like pancreatic cancer..

早期的肿瘤起源检测研究未能显示出益处，但这些试验在免疫治疗出现之前，没有能力指导患者进行靶向治疗，并且存在其他局限性，例如肿瘤类型过多，没有良好的治疗方法，如胰腺癌。。

With the advent of more modern site-specific chemo regimens — and more recently, molecularly targeted treatments and immunotherapies — there are now possibilities for improvement, as long as both the molecular and biological nature of a patient's cancer can be untangled.

随着更现代的特定部位化疗方案的出现，以及最近的分子靶向治疗和免疫疗法的出现，只要能够解开患者癌症的分子和生物学性质，现在就有改进的可能性。

In the newly published study, investigators led by senior author Anthony Greco, an oncologist with Tennessee Oncology and cofounder of the Sarah Cannon Research Institute, analyzed data collected by Hologic's Biotheranostics on patients who received testing that included a combination of the company's 93-gene expression assay, CancerType ID, and molecular profiling performed by NeoGenomics..

在这项最新发表的研究中，由田纳西州肿瘤学资深作者安东尼·格雷科（AnthonyGreco）领导的研究人员分析了Hologic的生物疗法（Biotheranostics）收集的患者数据，这些患者接受了包括该公司93基因表达测定，癌症类型ID和新基因组学进行的分子谱分析相结合的测试。。

Greco, who is also an adviser to Biotheranostics, said the two companies currently comarket their tests, with NeoGenomics targeted sequencing-based NeoType assays serving as a reflex for patients who have a tumor origin predicted by CancerType ID. Patients who receive certain CancerType results might have site-specific NeoType tests, while others might get pan-cancer sequencing..

Greco同时也是Biotheranostics的顾问，他说这两家公司目前正在共同营销他们的测试，新基因组学靶向测序的新类型检测可以作为癌症ID预测肿瘤起源的患者的反射。接受某些癌症类型结果的患者可能会进行特定部位的新类型检测，而其他患者可能会进行泛癌测序。。

Investigators mined Biotheranostics' MOSAIC database cataloging the rate of cancer type identifications and the frequency of actionable biomarkers in a select set of genes, including KRAS, IDH1/2, BRCA1/2, and BRAF.

研究人员挖掘了Biotheranostics的MOSAIC数据库，该数据库对癌症类型鉴定的比率和一组选定基因（包括KRAS，IDH1/2，BRCA1/2和BRAF）中可行生物标志物的频率进行了分类。

The team reported that CancerType ID identified a specific tumor type in nearly 93 percent (2,929 of 3,168) of CUP cases in the MOSAIC database. The most commonly identified histological type was adenocarcinoma, at 75 percent, with pancreaticobiliary being the most common molecularly diagnosed cancer, at 25 percent.

该团队报告说，在MOSAIC数据库中，近93%（3168例中的2929例）的CUP病例中，CancerType ID识别出特定的肿瘤类型。最常见的组织学类型是腺癌，占75%，胰胆管癌是最常见的分子诊断癌症，占25%。

Alterations in KRAS, IDH1/2, BRCA, and BRAF genes were identified in 19 percent of biopsies. A cancer-specific US Food and Drug Administration-approved or investigational targeted therapy was potentially available for 25 percent of these patients..

在19%的活检中发现了KRAS，IDH1/2，BRCA和BRAF基因的改变。美国食品和药物管理局批准的癌症特异性或研究性靶向治疗可能适用于25%的患者。。

Greco said that while the current report concentrated on a subset of oncogenes, the group has studied many others that could aid in personalized treatment decision-making, despite not being FDA-approved for the specific tumor types CancerType ID predicts.

格雷科说，虽然目前的报告集中在癌基因的一个子集上，但该小组研究了许多其他可能有助于个性化治疗决策的基因，尽管尚未获得FDA批准用于特定肿瘤类型CancerType ID预测。

Being a retrospective database, without patients' clinical treatment details, MOSAIC didn't offer the authors the opportunity to analyze how many patients eligible for a targeted therapy actually got one or track their outcomes.

作为一个回顾性数据库，没有患者的临床治疗细节，MOSAIC没有为作者提供机会来分析有多少符合靶向治疗条件的患者实际上得到了一个或跟踪他们的结果。

But evidence from the most recent studies of site-specific molecularly targeted or immunotherapy treatment in CUP patients has made clear that it improves patient outcomes compared to those treated without this information available, Greco said this week.

但格雷科本周表示，最近对CUP患者进行的位点特异性分子靶向或免疫治疗研究的证据表明，与没有这些信息的患者相比，它可以改善患者的预后。

One such study, the CUPISCO trial, found in 2023 that genomic profiling and molecularly guided treatment improved outcomes for patients with CUP. In that trial, newly diagnosed patients were randomized to receive either routine platinum-based chemotherapy or targeted therapy and cancer immunotherapy guided by comprehensive genomic profiling.

其中一项研究CUPISCO试验于2023年发现，基因组分析和分子指导治疗改善了CUP患者的预后。在该试验中，新诊断的患者被随机分配接受常规铂类化疗或靶向治疗以及在全面基因组分析指导下的癌症免疫治疗。

They were not tested for their cancer type or tissue of origin..

他们没有接受癌症类型或起源组织的检测。。

Greco highlighted another study, published earlier this year in Lancet Oncology, in which investigators found that patients with CUP whose treatment was guided by a Canhelp-Origin — a gene expression test similar to CancerType ID — with subsequent biomarker analysis had improved survival compared to those who received empirical chemotherapy.

格雷科强调了今年早些时候发表在《柳叶刀肿瘤学》上的另一项研究，研究人员发现，与接受经验性化疗的患者相比，接受Canhelp起源（一种类似于癌症类型ID的基因表达测试）指导治疗的CUP患者的生存率有所提高。

Median overall survival was 28.2 months in the site-specific therapy group and 19.0 months in the empirical chemotherapy group..

位点特异性治疗组的中位总生存期为28.2个月，经验性化疗组为19.0个月。。

Canhelp Genomics, the test's developer, is currently seeking strategic partnerships to help secure regulatory approval in the US and other countries.

该测试的开发人员Canhelp Genomics目前正在寻求战略合作伙伴关系，以帮助获得美国和其他国家的监管批准。

Greco said that with the weight of evidence demonstrating a benefit, additional randomized trials that include an untested empiric chemotherapy arm would be unethical at this point, but he believes other study designs could still help build clinical utility evidence.

格雷科说，随着大量证据表明有益，包括未经测试的经验性化疗组在内的其他随机试验在这一点上是不道德的，但他相信其他研究设计仍有助于建立临床实用性证据。

Additionally, he and his colleagues' discovery of pooled groups of patients with certain types of CUP findings also speaks to the value of gene-expression-based cancer type testing.

此外，他和他的同事发现了具有某些类型CUP发现的合并患者群体，这也说明了基于基因表达的癌症类型检测的价值。

For example, Greco highlighted work he and his team published on occult kidney cancers presenting as CUP, which they were able to substantiate using immunohistochemistry. That study included 24 cases with malignant cancer and no evidence of a primary tumor, with CancerType ID results indicating kidney cancer, but Greco said he has seen many more since then..

例如，格雷科强调了他和他的团队发表的关于隐匿性肾癌表现为CUP的研究，他们能够使用免疫组织化学证实这一点。这项研究包括24例恶性肿瘤患者，没有原发肿瘤的证据，癌症ID结果表明患有肾癌，但格雷科说，自那时以来，他已经看到了更多。。

'If you treat them as renal cell carcinoma, for instance, with immunotherapy, they do remarkably well. That's what they have. It's just that you have to diagnose them properly in order to know how to treat them,' Greco said.

“例如，如果你用免疫疗法将其视为肾细胞癌，它们会表现得非常好。这就是他们拥有的。格雷科说，只是你必须正确诊断它们，才能知道如何治疗它们。

He and his colleagues have also seen cases amassing of CancerType ID-predicted lung adenocarcinoma presenting without a primary site, again confirmed by immunohistochemistry.

他和他的同事还发现了大量癌症ID型预测的肺腺癌病例，这些病例没有原发部位，免疫组织化学再次证实了这一点。

'We've used this test in over 1,600 patients, so we have a wealth of experience. The fact that all CUP comes from specific cancers is becoming clear now, and most experts who see what's happening in the evolving data, they don't challenge it anymore,' Greco said.

“我们已经在1600多名患者中使用了这种测试，因此我们有丰富的经验。格雷科说，所有奖杯都来自特定的癌症这一事实现在变得越来越清楚，大多数看到不断变化的数据发生了什么的专家，他们不再挑战它了。

Several companies offering comprehensive genomic sequencing have shared in recent years that they are working with algorithmic or AI tools that can glean tumor type, or origin, from their genomic data. These include Caris Life Sciences, which has been offering an AI-driven tumor origin predictor, MI GPSai, since December 2019.

近年来，几家提供全面基因组测序的公司分享了他们正在使用算法或AI工具，这些工具可以从他们的基因组数据中收集肿瘤类型或起源。其中包括Caris Life Sciences，该公司自2019年12月以来一直提供AI驱动的肿瘤起源预测因子MI GPSai。

The company has published results showing 93 percent success in determining an origin across cancers, but only about a 72 percent rate for CUP cases. .

该公司公布的结果显示，93%的成功率确定了各种癌症的起源，但CUP病例的成功率仅为72%。

Memorial Sloan Kettering has also recently made similar forays using its MSK-IMPACT genomic profiling assay.

Memorial Sloan Kettering最近也使用其MSK-IMPACT基因组分析方法进行了类似的尝试。

Greco cautioned that these other tools haven't been specifically validated in a CUP population as performance in a larger group of cancers doesn't necessarily translate to success in the CUP population.

格雷科提醒说，这些其他工具尚未在CUP人群中得到特别验证，因为在更大范围的癌症中的表现不一定会转化为CUP人群的成功。

'I'm an adviser to Biotheranostics, but I don't believe I am biased. If they can validate that their tests are accurate in unknown primary cancer, then I'm going to applaud them, but they haven't done that yet,' Greco said. 'It's easy if you see several mutations that are usually seen in lung cancer, and you say, 'Yeah that's probably lung cancer.' But [in CUP] there are many overlapping mutations and many cancer types.'.

“我是生物疗法的顾问，但我不认为我有偏见。格雷科说，如果他们能够验证他们的测试在未知原发癌中的准确性，那么我会为他们鼓掌，但他们还没有做到这一点但是[在CUP中]有许多重叠突变和许多癌症类型。”。