Quantitative Histomorphometric Risk Classifier (QuHbIC) in HPV + Oropharyngeal Carcinoma

HPV 口咽癌的定量组织形态学风险分类器 (QuHbIC)

• 批准号: 10574506
• 负责人: SHLOMO KOYFMAN
• 金额: $ 59.25万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-08 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10574506
• 关键词: Adoption; Adult; Aftercare; American Joint Committee on Cancer; Architecture; Cancer Diagnostics; Categories; Cervical; Cessation of life; Chemotherapy and/or radiation; Chromosome abnormality; Classification; Clinic; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Collaborations; Complex; Computer Assisted; Computer Vision Systems; Computer software; Data; Diagnosis; Diagnostic tests; Disease; Distant; Distant Metastasis; Dose; Eligibility Determination; Environment; Epithelium; Failure; Foundations; HPV oropharyngeal cancer; HPV-High Risk; Head Cancer; Health Care Costs; Hematoxylin and Eosin Staining Method; Human Papillomavirus; Image; Indolent; Institution; International Union Against Cancer; Left; Malignant Neoplasms; Measurement; Mediating; Modeling; Molecular; Morbidity - disease rate; Morphology; Multivariate Analysis; Mutation; Neck Cancer; Nuclear; Oropharyngeal Squamous Cell Carcinoma; Outcome; Pathology; Patient-Focused Outcomes; Patients; Pattern; Pattern Recognition; Phase; Process; Production; Prognosis; Progressive Disease; Publishing; Radiation Therapy Oncology Group; Radiation therapy; Randomized; Randomized Controlled Clinical Trials; Recurrence; Recurrent disease; Regimen; Regulatory Pathway; Research Personnel; Resources; Retrospective cohort; Risk; Shapes; Site; Slide; Smoking; Specimen; Squamous cell carcinoma; Stage Grouping; Stains; Stratification; Surgical Oncology; Surgical Pathology; Surrogate Markers; Survival Rate; System; Testing; Texture; Time; Tissue Stains; Tissues; Training; Treatment Failure; Tumor-Infiltrating Lymphocytes; Universities; Uterus; Validation; Visual; Work; behavioral outcome; chemoradiation; chemotherapy; cohort; commercial prototype; commercialization; common treatment; companion diagnostics; computerized; cost; density; diagnostic tool; digital imaging; digital pathology; disorder risk; economic need; high risk; human papilloma virus oropharyngeal squamous cell carcinoma; improved; improved outcome; industry partner; innovation; malignant oropharynx neoplasm; mouth squamous cell carcinoma; neoplastic cell; outcome prediction; overtreatment; participant enrollment; patient subsets; pharynx squamous cell carcinoma; precision medicine; prognostic; prognostic assays; prognostication; prospective; prototype; randomized, clinical trials; risk stratification; success; tool; treatment choice; treatment response; treatment risk; tumor; tumor behavior

SUMMARY: In 2016, nearly 50,000 adults in the US were diagnosed with oral and pharyngeal squamous cell carcinoma (SCC), and nearly 10,000 died from the disease. Human papillomavirus (HPV) is now recognized as the most common cause of oropharyngeal (OP) SCC in the US. Although concomitant chemo- and radio-therapy is the most common treatment choice in patients with advanced OP-SCC, they have substantial short- and long- term morbidity and result in increased health care costs in patients who are cured of their cancers. These patients live with sometimes disabling morbidity for many years post-treatment. For these reasons, it has been suggested that therapy in lower risk patients might be de-escalated. There is also a higher risk cohort of patients in whom treatment with chemo-radiation may be insufficient, often resulting in distant metastatic failure. As such, these patients may require intensified therapies to improve outcomes. This is an agonizing choice for patients and their doctors, however. While patients do not want to be sickened by morbid treatments, they are obviously concerned about having the best chance at cure. Unfortunately, there currently are no companion diagnostic tools to identify which HPV + OPSCC patients are at (1) low risk of recurrence such that they can be treated safely to high cure rates with de-escalated therapy; (2) higher risk of failure despite aggressive high dose chemoradiation in whom treatment intensification strategies should be studied. Recently, we developed a quantitative histomorphometric based image risk classifier (QuHbIC) that uses computerized measurements of tumor morphology (e.g. nuclear orientation, texture, shape, architecture) from digital images of H&E-stained tumor sections to predict progression in HPV+ OP-SCC patients; the current version of QuHbIC has already been validated in >400 patients and found to be superior to clinical variables in outcome prediction. In this Academic-Industry Partnership we seek to further improve predictive accuracy of QuHbIC by incorporating new classes of image features relating to stromal morphology, density and patterns of tumor infiltrating lymphocytes, and tumor cell multi-nucleation, features now recognized as promising markers of unfavorable prognosis in HPV+ OP-SCC. We also seek to create a pre-commercial QuHbIC companion diagnostic test that is ready for clinical use in risk stratification in p16+ OP-SCC. QuHbIC will be trained on >700 retrospectively identified HPV + OP-SCC whole tissue slide images with associated long term outcome data and then validated on 440 cases from randomized, controlled, multi-institutional RTOG 0129 and 0522 clinical trials. This partnership will leverage long-standing collaborations in (1) computational histomorphometry from the Madabhushi group at Case Western Reserve University, (2) surgical pathology and oncology expertise in HPV+ OPSCC from Vanderbilt University and the Cleveland Clinic and, (3) Inspirata Inc., a cancer diagnostics company that will bring quality management systems and production software standards to establish QuHbIC as an Affordable Precision Medicine (APM) solution for oropharyngeal cancers.

摘要：2016年，美国近50，000名成年人被诊断患有口腔和咽鳞状细胞癌。 癌症（SCC），近10，000人死于这种疾病。人乳头瘤病毒（HPV）目前被认为是 是美国口咽（OP）SCC的最常见原因。虽然伴随的化疗和放疗 是晚期OP-SCC患者最常见的治疗选择， 长期发病率并导致癌症治愈患者的医疗保健成本增加。这些患者 在治疗后的许多年里，有时会出现致残性疾病。出于这些原因，有人建议 低风险患者的治疗可能会降低。还有一组风险较高的患者， 用化学-放射治疗可能是不够的，常常导致远处转移失败。因此，这些 患者可能需要强化治疗以改善结果。这对病人来说是一个痛苦的选择， 然而，他们的医生。虽然病人不想被病态的治疗生病，他们显然是 担心有最好的治愈机会不幸的是，目前还没有伴随诊断 用于识别HPV + OPSCC患者的工具（1）复发风险低，因此可以治疗 降级治疗安全地达到高治愈率;（2）尽管积极的高剂量，但失败的风险较高 应研究其治疗强化策略。 最近，我们开发了一种基于定量组织形态学的图像风险分类器（QuHbIC）， 肿瘤形态学的计算机化测量（例如，核取向、纹理、形状、架构）， H& E染色肿瘤切片的数字图像，以预测HPV+ OP-SCC患者的进展;目前 QuHbIC版本已经在>400例患者中得到验证，并发现在以下方面上级临床变量： 结果预测在这个学术界和工业界的合作伙伴关系中，我们寻求进一步提高预测的准确性， QuHbIC通过合并与基质形态、密度和基质模式相关的新的图像特征类别， 肿瘤浸润淋巴细胞和肿瘤细胞多核化，现在被认为是有希望的肿瘤标志物。 HPV+ OP-SCC预后不良。我们还寻求创建一个商业化前的QuHbIC伴侣 p16+ OP-SCC的风险分层中准备好用于临床的诊断测试。QuHbIC将接受>700次培训 回顾性识别HPV + OP-SCC全组织切片图像及相关长期结局数据， 然后在随机、对照、多机构RTOG 0129和0522临床试验的440例病例中进行验证。 这种伙伴关系将利用（1）计算组织形态计量学的长期合作， 凯斯西储大学的Madabhushi小组，（2）外科病理学和肿瘤学专业知识， 来自范德比尔特大学和克利夫兰诊所的HPV+ OPSCC，以及（3）Inspirata Inc.，癌症诊断 公司将带来质量管理体系和生产软件标准，以建立QuHbIC 作为口咽癌的经济型精准医学（APM）解决方案。

项目成果

Radiomic Features Associated With HPV Status on Pretreatment Computed Tomography in Oropharyngeal Squamous Cell Carcinoma Inform Clinical Prognosis.

• DOI: 10.3389/fonc.2021.744250
• 发表时间: 2021
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 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
• 通讯作者: Madabhushi A