Clinical validation of a tissue-agnostic genome-wide methylome enrichment molecular residual disease assay for head and neck malignancies☆

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-01-01 DOI:10.1016/j.annonc.2024.08.2348

G. Liu , S.H. Huang , L. Ailles , K. Rey-McIntyre , C.A. Melton , S.Y. Shen , J.M. Burgener , B. Brown , J. Zhang , J. Min , Y. Wang , O. Hall , J.T. Jones , K. Budhraja , J.B. Provance , E.V. Sosa , A. Licon , A. Williams , S.V. Bratman , B.A. Allen , D.D. De Carvalho

{"title":"Clinical validation of a tissue-agnostic genome-wide methylome enrichment molecular residual disease assay for head and neck malignancies☆","authors":"G. Liu , S.H. Huang , L. Ailles , K. Rey-McIntyre , C.A. Melton , S.Y. Shen , J.M. Burgener , B. Brown , J. Zhang , J. Min , Y. Wang , O. Hall , J.T. Jones , K. Budhraja , J.B. Provance , E.V. Sosa , A. Licon , A. Williams , S.V. Bratman , B.A. Allen , D.D. De Carvalho","doi":"10.1016/j.annonc.2024.08.2348","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Outcomes for patients with locally advanced head and neck cancer (HNC) treated with curative intent remain disappointing, with 5-year survival rates at 50%. Most recurrences occur within the first 2 years after treatment, providing a window of opportunity to identify patients with molecular residual disease (MRD). A tissue-agnostic test for MRD detection in patients with human papillomavirus (HPV) positive and negative HNC, where tissue is often scarce, is needed.</div></div><div><h3>Patients and methods</h3><div>Patients with stage I-IVB HNC, including patients positive and negative for HPV, were enrolled and peripheral blood plasma was collected longitudinally at diagnosis and ∼3, 12, and 24 months after curative intent treatment. The full cohort includes 325 patients with 1155 samples. Samples were split into distinct sets to train and validate a classifier capable of identifying MRD using a tissue-agnostic genome-wide methylome enrichment platform. The primary endpoint was recurrence-free survival (RFS).</div></div><div><h3>Results</h3><div>With a median follow-up of 60 months, patients in the blinded validation set with MRD positivity experienced significantly worse RFS with a hazard ratio (HR) of 35.7 [95% confidence interval (CI) 10.8-117.8; <em>P</em> < 0.0001]. For patients with HPV negativity, HR was 42.3 (95% CI 9.8-182.3; <em>P</em> < 0.0001); for patients with HPV-positive oropharyngeal cancer, HR was 24.1 (95% CI 3.0-196.8; <em>P</em> < 0.0001). Moreover, the lead time between MRD positivity and clinical recurrence was up to 14.9 months, with a mean lead time of 4.1 months. Surveillance sensitivity was 91% (95% CI 77% to 97%) and specificity was 88% (95% CI 80% to 93%).</div></div><div><h3>Conclusions</h3><div>Here we validate the clinical performance characteristics of a tissue-agnostic genome-wide methylome enrichment assay for MRD detection in patients with HNC. The MRD detection test showed high sensitivity for identifying recurrence at high specificity across different anatomical sites, HPV status, and treatment regimens, highlighting the broad applicability for MRD detection in patients with HNC.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 108-117"},"PeriodicalIF":56.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0923753424039292","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Outcomes for patients with locally advanced head and neck cancer (HNC) treated with curative intent remain disappointing, with 5-year survival rates at 50%. Most recurrences occur within the first 2 years after treatment, providing a window of opportunity to identify patients with molecular residual disease (MRD). A tissue-agnostic test for MRD detection in patients with human papillomavirus (HPV) positive and negative HNC, where tissue is often scarce, is needed.

Patients and methods

Patients with stage I-IVB HNC, including patients positive and negative for HPV, were enrolled and peripheral blood plasma was collected longitudinally at diagnosis and ∼3, 12, and 24 months after curative intent treatment. The full cohort includes 325 patients with 1155 samples. Samples were split into distinct sets to train and validate a classifier capable of identifying MRD using a tissue-agnostic genome-wide methylome enrichment platform. The primary endpoint was recurrence-free survival (RFS).

Results

With a median follow-up of 60 months, patients in the blinded validation set with MRD positivity experienced significantly worse RFS with a hazard ratio (HR) of 35.7 [95% confidence interval (CI) 10.8-117.8; P < 0.0001]. For patients with HPV negativity, HR was 42.3 (95% CI 9.8-182.3; P < 0.0001); for patients with HPV-positive oropharyngeal cancer, HR was 24.1 (95% CI 3.0-196.8; P < 0.0001). Moreover, the lead time between MRD positivity and clinical recurrence was up to 14.9 months, with a mean lead time of 4.1 months. Surveillance sensitivity was 91% (95% CI 77% to 97%) and specificity was 88% (95% CI 80% to 93%).

Conclusions

Here we validate the clinical performance characteristics of a tissue-agnostic genome-wide methylome enrichment assay for MRD detection in patients with HNC. The MRD detection test showed high sensitivity for identifying recurrence at high specificity across different anatomical sites, HPV status, and treatment regimens, highlighting the broad applicability for MRD detection in patients with HNC.

查看原文本刊更多论文

头颈部恶性肿瘤组织诊断性全基因组甲基组富集分子残留病检测的临床验证。

背景：接受根治性治疗的局部晚期头颈癌（HNC）患者的疗效仍然令人失望，5年生存率仅为50%。大多数复发发生在治疗后的头两年内，这为鉴别分子残留病（MRD）患者提供了机会之窗。人乳头瘤病毒（HPV）阳性和阴性HNC患者的组织往往很少，因此需要一种组织诊断检验来检测MRD：入组 I-IVB 期 HNC 患者，包括 HPV 阳性和阴性患者，在诊断时、治愈性治疗后 3 个月、12 个月和 24 个月纵向采集外周血血浆。整个队列包括 325 名患者和 1155 份样本。样本被分成不同的组，利用组织诊断全基因组甲基组富集平台训练和验证能够识别MRD的分类器。主要终点是无复发生存期（RFS）：中位随访时间为60个月，在盲法验证组中，MRD阳性患者的RFS明显降低，危险比（HR）为35.7 [95%置信区间（CI）10.8-117.8；P < 0.0001]。HPV阴性患者的HR为42.3 (95% CI 9.8-182.3; P < 0.0001)；HPV阳性口咽癌患者的HR为24.1 (95% CI 3.0-196.8; P < 0.0001)。此外，MRD阳性与临床复发之间的间隔时间长达14.9个月，平均间隔时间为4.1个月。监测敏感性为91%（95% CI为77%至97%），特异性为88%（95% CI为80%至93%）：我们在此验证了用于检测HNC患者MRD的组织诊断性全基因组甲基组富集测定的临床性能特征。在不同的解剖部位、HPV 状态和治疗方案中，MRD 检测试验都显示出了高灵敏度和高特异性的复发识别能力，这突出表明了 MRD 检测在 HNC 患者中的广泛适用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.