Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification.
Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification.
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DOI：
10.1016/j.ebiom.2022.104373
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发表时间：
2022-12
期刊：
影响因子：
11.1
通讯作者：
Nicholsa, Anthony C.
中科院分区：
文献类型：
--
作者：
Zeng, Peter Y. F.;Cecchini, Matthew J.;Barrett, John W.;Shammas-Toma, Matthew;De Cecco, Loris;Fini, Mara S. Sera;Cavalieri, Stefano;Licitra, Lisa;Hoebers, Frank;Brakenhoff, Ruud H.;Leemans, C. Rene;Scheckenbach, Kathrin;Poli, Tito;Wang, Xiaowei;Liu, Xinyi;Laxague, Francisco;Prisman, Eitan;Peh, Catherine;Bose, Pinaki;Dort, Joseph C.;Shaikh, Mushfiq H.;Ryan, Sarah E. B.;Dawson, Alice;Khan, Mohammed I.;Howlett, Christopher J.;Stecho, William;Plantinga, Paul;da Silva, Sabrina Daniela;Hier, Michael;Khan, Halema;MacNeil, Danielle;Mendez, Adrian;Yoo, John;Fung, Kevin;Lang, Pencilla;Winquist, Eric;Palma, David A.;Ziai, Hedyeh;Amelio, Antonio L.;Li, Shawn S-C.;Boutros, Paul C.;Mymryk, Joe S.;Nicholsa, Anthony C.
关键词：
考虑到一般良好的预后，对人乳头瘤病毒相关（HPV+）口咽鳞状细胞癌（OPSCC）患者的治疗降级有很大的兴趣。然而，15-30%的患者在初次治疗后复发，反映了对改进风险分层工具的需求。我们试图开发一种分子检测来对HPV+ OPSCC患者进行风险分层。我们在包括906例患者的6个独立队列中创建了与生存结局相关的免疫评分（UWO 3），包括盲法回顾性和前瞻性外部验证。两个积极的辐射降级队列用于评估UWO 3识别复发患者的能力。多变量考克斯模型用于评估UWO 3免疫类别与结果之间的关联。三基因免疫评分将患者分为三种免疫类别（免疫丰富，混合或免疫沙漠），并与六个数据集（包括大型回顾性和前瞻性数据集）的无病生存率密切相关。合并分析表明，在调整年龄、性别、吸烟状况和AJCC 8临床分期后，免疫丰富组的无病生存率上级免疫沙漠组（HR = 9.0，95% CI：3.2-25.5，P = 3.6 × 10−5）和混合组（HR = 6.4，95% CI：2.2-18.7，P = 0.006）。最后，UWO 3能够从两个小的治疗降级队列中识别出在积极降级至30戈伊辐射后仍无疾病的患者。通过额外的前瞻性验证，UWO 3评分可以基于6个独立队列的稳健结局预测，为HPV+ OPSCC患者提供生物标志物驱动的临床决策。目前正在计划进行前瞻性降级和强化临床试验。CIHR、欧盟和NIH。
There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15–30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ OPSCC patients. We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes. A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2–25.5, P = 3.6 × 10−5) and mixed (HR = 6.4, 95% CI: 2.2–18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation. With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned. CIHR, European Union, and the NIH.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.5
作者：
Gu, Yi;Chae, Hee-Don;Williams, David A.
通讯作者：
Williams, David A.