多靶点血液检测可检测肝硬化后的肝癌

StephenW

多靶点血液检测可检测肝硬化后的肝癌

Jagpreet Chhatwal 博士

根据 2022 年 ASCO 胃肠癌研讨会上提出的一项建模研究，对于肝硬化患者的监测，一项新的血液检测在早期发现的肝细胞癌比超声检查更多。

研究人员 Jagpreet Chhatwal 博士表示，临床指南建议使用或不使用血清生物标志物甲胎蛋白 (AFP) 的超声来监测有 HCC 风险的个体，但只有大约四分之一的患者坚持这种做法。波士顿麻省总医院技术评估研究所所长和哈佛医学院助理教授 Chhatwal 博士补充说，只有三分之一的 HCC 患者在出现症状之前被诊断出来。

新的血液检测是一种多靶点血液检测 (mt-HBT)，包含四种甲基化 DNA 标记和两种蛋白质标记，在之前的研究中显示出对早期肝细胞癌 (HCC) 的敏感性。该测试由 Exact Sciences 开发，已获得 FDA 的突破性设备指定。

“通过减少监测障碍和提高依从性，mt-HBT 可以改善早期肝癌的检测，并且可能是肝硬化患者监测的一个有希望的选择，”Chhatwal 博士说。

研究人员开发了 30 年期间代偿期肝硬化（Child-Pugh A 级）患者 HCC 自然史的微观模拟模型。模拟人口平均年龄为 51 岁，男性占 71%；基础疾病病因主要是丙型肝炎（29%）、乙型肝炎（11%）、酒精相关性肝病（22%）和非酒精性脂肪肝（29%）。从已发表的研究中提取模型参数，并从文献中估计对监测的依从性。

该研究比较了无监测与仅使用超声、仅 AFP、超声加 AFP、mt-HBT 和 mt-HBT 的两年监测与“改进”的依从性（即遵守推荐的一年两次检测的时间表）（摘要 405）。

该团队根据已发表研究的信息估计了这些测试的性能。 Chhatwal 博士说：“我们假设在没有超声的情况下进行基于血液的测试，可以将监测依从性提高 10%，也就是说，与目前的情况相比，绝对提高了大约 4%”。

使用 mt-HBT/Surveillance Combo 进行最佳检测

每 100,000 名发展为早期 HCC 的肝硬化患者，mt-HBT 比 AFP 多 57%，比超声多 21%，但比超声加 AFP 少 3%（表）。 Chhatwal 博士报告说，随着依从性的提高，mt-HBT 检测出的早期 HCC 比超声加 AFP 多 3%。
桌子。每 100,000 名肝硬化患者通过监测发现的 HCC 病例
模态 早期 晚期 总检测
                       HCC, n HCC, n 率 %
%
法新社 3,965 1,301 5,266 30.4
超声 5,138 1,879 7,017 40.4
超声加 AFP 6,420 1,526 7,946 45.8
吨-HBT 6,216 1,695 7,911 45.6
mt-HBT 依从性提高 6,632 1,754 8,385 48.3

AFP，甲胎蛋白； mt-HBT，多靶点血液检测。

与无监测相比，mt-HBT 提供的患者生命年比 AFP 多 53%，比超声多 21%，但比超声加 AFP 组合的生命年少 1%。 mt-HBT 获得的生活质量年比 AFP 增加 18%，比超声增加 7%，但比超声加 AFP 监测减少 0.3%。

同样，随着对 mt-HBT 监测的依从性提高，结果比超声加 AFP 有所改善，并且该测试产生了 3% 的生命年和 2% 的生命质量年。

需要更多研究

尽管用于 HCC 监测的 mt-HBT 血液检测获得了突破性的称号，但肝病专家 Augusto Villanueva Rodriguez 医学博士表示，他将推迟在学术实践中使用它。 “这次验血的表现不错，但仍然不是很好。纽约市西奈山伊坎医学院的医学副教授维拉纽瓦罗德里格斯博士说，我想等待一个表现出色的人在我的实践中使用它。

他指出，模拟研究假设，根据现有数据，如果严格遵守监测计划，mt-HBT 测试将提高 10% 的 HCC 检测率。结果是增长了 3%，他说，这“并不是一个巨大的进步”。

——卡罗琳·赫尔维克

该研究由 Exact Sciences 资助。 Chhatwal 博士报告了与拜耳和熨斗的财务关系，并担任价值分析实验室的合作伙伴。 Villanueva Rodriguez 博士报告没有相关的财务披露。

StephenW

Multiple-Target Blood Test Detects Liver Cancer After Cirrhosis

Jagpreet Chhatwal, PhD

For surveillance of patients with cirrhosis, a novel blood test found more hepatocellular carcinoma at an early stage than ultrasound, according to a modeling study presented at the 2022 ASCO Gastrointestinal Cancers Symposium.

Clinical guidelines recommend ultrasound with or without the serum biomarker alpha-fetoprotein (AFP) for the surveillance of individuals at risk for HCC, but only about one-fourth of patients adhere to this practice, according to investigator Jagpreet Chhatwal, PhD. Only one- third of patients who develop HCC are diagnosed before developing symptoms, added Dr. Chhatwal, the director of the Institute for Technology Assessment at Massachusetts General Hospital and an assistant professor at Harvard Medical School, both in Boston.

The new blood test, a multiple-target blood-based test (mt-HBT) that incorporates four methylated DNA markers and two protein markers has shown sensitivity for early-stage hepatocellular carcinoma (HCC) in previous studies. The test, developed by Exact Sciences, has been granted a breakthrough device designation by the FDA.

“By decreasing surveillance barriers and increasing adherence, mt-HBTs could improve the detection of liver cancer at an early stage and could be a promising option for surveillance in patients with cirrhosis,” Dr. Chhatwal said.

The researchers developed a microsimulation model of the natural history of HCC in patients with compensated cirrhosis (Child-Pugh class A) over a 30-year period. The simulated population was an average age of 51 years and 71% male; underlying disease etiology was mainly hepatitis C (29%), hepatitis B (11%), alcohol-associated liver disease (22%) and nonalcoholic fatty liver disease (29%). Model parameters were extracted from published studies, and adherence to surveillance was estimated from the literature.

The study compared no surveillance with biannual surveillance using ultrasound only, AFP only, ultrasound plus AFP, mt-HBT, and mt-HBT with “improved” adherence (i.e., adherence to the recommended schedule of biannual testing) (abstract 405).

The team estimated the performance of these tests based on information from published studies. “We assumed a blood-based test, without ultrasound, would improve surveillance adherence by 10%—that is, showing about a 4% absolute improvement” over the current scenario , Dr. Chhatwal said.

Best Detection With mt-HBT/Surveillance Combo

Per 100,000 cirrhosis patients who developed early-stage HCC, mt-HBT detected 57% more than AFP and 21% more than ultrasound, but 3% less than ultrasound plus AFP (Table). With the addition of improved adherence, mt-HBT detected 3% more early-stage HCC than ultrasound plus AFP, Dr. Chhatwal reported.
Table. Cases of HCC Detected Via Surveillance Per 100,000 Cirrhosis Patients
Modality Early-stage Late-stage Total Detection
                       HCC, n HCC, n rate %
%
AFP 3,965 1,301 5,266 30.4
Ultrasound 5,138 1,879 7,017 40.4
Ultrasound plus AFP 6,420 1,526 7,946 45.8
mt-HBT 6,216 1,695 7,911 45.6
mt-HBT with improved adherence 6,632 1,754 8,385 48.3

AFP, alpha-fetoprotein; mt-HBT, multiple-target blood-based test.

Compared with no surveillance, mt-HBT provided 53% more patient life-years than AFP and 21% more life-years than ultrasound but 1% fewer life-years than the ultrasound plus AFP combination. Quality-of-life years gained with mt -HBT were 18% more than with AFP and 7% more than with ultrasound, but 0.3% fewer than with ultrasound plus AFP surveillance.

Similarly, with the addition of improved adherence to mt-HBT surveillance, outcomes improved over ultrasound plus AFP, and the test yielded 3% more life-years and 2% more quality-of-life years.

A Need for More Research

Although the mt-HBT blood test for HCC surveillance received a breakthrough designation, liver disease specialist Augusto Villanueva Rodriguez, MD, PhD, said he will hold off using it in his academic practice. “The performance of this blood test is good but still not excellent. I want to wait for one with excellent performance before using it in my practice,” said Dr. Villanueva Rodriguez, an associate professor of medicine at the Icahn School of Medicine at Mount Sinai, in New York City.

He noted that the simulation study assumed, based on available data, that with good adherence to the surveillance schedule, the mt-HBT test would improve HCC detection by 10%. The result was a 3% increase, which, he said, was “ not a huge improvement.”

—Caroline Helwick

The study was funded by Exact Sciences. Dr. Chhatwal reported financial relationships with Bayer and Flatiron, and serving as a partner with Value Analytics Labs. Dr. Villanueva Rodriguez reported no relevant financial disclosures.