Radiomic Features Associated With HPV Status on Pretreatment Computed Tomography in Oropharyngeal Squamous Cell Carcinoma Inform Clinical Prognosis.
Radiomic Features Associated With HPV Status on Pretreatment Computed Tomography in Oropharyngeal Squamous Cell Carcinoma Inform Clinical Prognosis.
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DOI：
10.3389/fonc.2021.744250
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发表时间：
2021
影响因子：
4.7
通讯作者：
Madabhushi A
中科院分区：
文献类型：
--
作者：
Song B;Yang K;Garneau J;Lu C;Li L;Lee J;Stock S;Braman NM;Koyuncu CF;Toro P;Fu P;Koyfman SA;Lewis JS Jr;Madabhushi A
缺乏准确预测人乳头瘤病毒相关 (HPV+) 和烟草和酒精相关 (HPV−) 口咽鳞状细胞癌 (OPSCC) 结果的生物标志物。本研究的目的是 i) 通过 CT 扫描开发和评估肿瘤内（瘤内）和肿瘤周围（瘤周）的放射组学特征，以预测 HPV 状态； ii) 研究 HPV− 和 HPV+ 患者放射组学特征的预后价值，包括在 AJCC 第八版定义的各个分期组内； iii) 开发和评估涉及放射组学、临床和病理因素的临床病理成像列线图，用于 HPV+ 患者的无病生存 (DFS) 预测。这项回顾性研究包括 582 名 OPSCC 患者，其中 462 名来自癌症影像档案 (TCIA)，具有可用的肿瘤分割，120 名来自克利夫兰诊所基金会 (CCF，表示为 SCCF)，患有 HPV+ OPSCC。我们根据 HPV 状态预测的大约 3:5 比例将 TCIA 队列细分为训练（ST，180 名患者）和验证（SV，282 名患者）。使用 ST 通过最小冗余最大相关性 (MRMR) 选择与 HPV 状态相关的前 15 个放射组学特征，并在 SV 上进行评估。利用这 15 个最重要的 HPV 状态相关特征中的 3 个，我们通过 Cox 回归模型为 HPV+ (RRSHPV+) 和 HPV− 患者 (RRSHPV−) 创建了放射组学风险评分，以预测 DFS。 RRSHPV+ 在 SCCF 上得到了进一步的外部验证。构建了 HPV+ 人群 (Mp+RRS) 的列线图。 RRSHPV+ 和 Mp+RRS 分别用于预测 AJCC 第八版定义的 I 期、II 期和 III 期患者的 DFS。 RRSHPV+ 对 i) 整个 HPV+ 人群 [风险比 (HR) = 1.97，95% 置信区间 (CI)：1.35–2.88，p < 0.001]，ii) AJCC 第八 I 期人群（HR = 1.99，95% CI：1.04–3.83，p = 0.039）和 iii) 的 DFS 具有预后意义AJCC 第八期 II 期人群（HR = 3.61，95% CI：1.71–7.62，p < 0.001）。 HPV+ 列线图 Mp+RRS（C 指数，0.59；95% CI：0.54–0.65）也是 DFS 的预后（HR = 1.86，95% CI：1.27–2.71，p = 0.001）。基于 CT 的放射组学特征与 OPSCC 患者的 HPV 状态和 DFS 相关。经过额外的验证，放射组学特征及其相应的列线图有可能用于识别可能是去强化治疗候选者的 HPV+ OPSCC 患者。
There is a lack of biomarkers for accurately prognosticating outcome in both human papillomavirus-related (HPV+) and tobacco- and alcohol-related (HPV−) oropharyngeal squamous cell carcinoma (OPSCC). The aims of this study were to i) develop and evaluate radiomic features within (intratumoral) and around tumor (peritumoral) on CT scans to predict HPV status; ii) investigate the prognostic value of the radiomic features for both HPV− and HPV+ patients, including within individual AJCC eighth edition-defined stage groups; and iii) develop and evaluate a clinicopathologic imaging nomogram involving radiomic, clinical, and pathologic factors for disease-free survival (DFS) prediction for HPV+ patients. This retrospective study included 582 OPSCC patients, of which 462 were obtained from The Cancer Imaging Archive (TCIA) with available tumor segmentation and 120 were from Cleveland Clinic Foundation (CCF, denoted as SCCF) with HPV+ OPSCC. We subdivided the TCIA cohort into training (ST, 180 patients) and validation (SV, 282 patients) based on an approximately 3:5 ratio for HPV status prediction. The top 15 radiomic features that were associated with HPV status were selected by the minimum redundancy–maximum relevance (MRMR) using ST and evaluated on SV. Using 3 of these 15 top HPV status-associated features, we created radiomic risk scores for both HPV+ (RRSHPV+) and HPV− patients (RRSHPV−) through a Cox regression model to predict DFS. RRSHPV+ was further externally validated on SCCF. Nomograms for the HPV+ population (Mp+RRS) were constructed. Both RRSHPV+ and Mp+RRS were used to prognosticate DFS for the AJCC eighth edition-defined stage I, stage II, and stage III patients separately. RRSHPV+ was prognostic for DFS for i) the whole HPV+ population [hazard ratio (HR) = 1.97, 95% confidence interval (CI): 1.35–2.88, p < 0.001], ii) the AJCC eighth stage I population (HR = 1.99, 95% CI: 1.04–3.83, p = 0.039), and iii) the AJCC eighth stage II population (HR = 3.61, 95% CI: 1.71–7.62, p < 0.001). HPV+ nomogram Mp+RRS (C-index, 0.59; 95% CI: 0.54–0.65) was also prognostic of DFS (HR = 1.86, 95% CI: 1.27–2.71, p = 0.001). CT-based radiomic signatures are associated with both HPV status and DFS in OPSCC patients. With additional validation, the radiomic signature and its corresponding nomogram could potentially be used for identifying HPV+ OPSCC patients who might be candidates for therapy deintensification.
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