Oral Cavity Quantitative Histomorphometric Risk Classifier (OHbIC) in Oral Cavity Squamous Cell Carcinoma (OC-SCC)

口腔鳞状细胞癌 (OC-SCC) 中的口腔定量组织形态风险分类器 (OHbIC)

• 批准号: 10726124
• 负责人: JAMES LEWIS
• 金额: $ 65.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10726124
• 关键词: Adjuvant; Adjuvant Chemotherapy; Adjuvant Therapy; Adoption; Adult; Age; American Cancer Society; American Joint Committee on Cancer; Architecture; Biological Assay; Cancer Center; Categories; Cells; Cessation of life; Classification; Clinic; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Clinical stratification; Cloud Computing; Collaborations; Computer Assisted; Computer Vision Systems; Diagnosis; Disease; Eligibility Determination; European Organization for Research and Treatment of Cancer; Excision; Foundations; Head and neck structure; Hematoxylin and Eosin Staining Method; Histologic; Image; India; Institution; Invaded; Left; Malignant Neoplasms; Measurement; Measures; Modeling; Molecular; Morphology; Nuclear; Operative Surgical Procedures; Oral cavity; Outcome; Patient Selection; Patient risk; Patient-Focused Outcomes; Patients; Pattern; Pattern Recognition; Platinum; Postoperative Period; Prognostic Marker; Radiation; Radiation Therapy Oncology Group; Radiation therapy; Recurrence; Regimen; Relapse; Resources; Risk; Risk Marker; San Francisco; Shapes; Slide; Smoking; Staging; Stains; Standardization; Surgical Oncology; Surgical Pathology; System; Systemic Therapy; Testing; Texture; Therapeutic; Tissue Microarray; Tissue Stains; Tissues; Training; Tumor Cell Invasion; Tumor stage; Tumor-Infiltrating Lymphocytes; United States; United States National Institutes of Health; Universities; Validation; Visual; Woman; Work; advanced disease; behavioral outcome; chemoradiation; chemotherapy; cohort; collaborative trial; companion diagnostics; computerized; cost; density; diagnostic tool; digital; digital imaging; high risk; high risk population; improved; innovation; lymphatic Invasion; malignant mouth neoplasm; men; mouth squamous cell carcinoma; neoplastic cell; outcome prediction; patient prognosis; patient stratification; perineural; precision medicine; predict clinical outcome; predictive marker; predictive test; prognostic; prognostic assays; prognostic of survival; prognostication; progression risk; prospective; risk stratification; success; targeted treatment; tool; treatment choice; tumor; tumor behavior

SUMMARY: In 2018, nearly 34,000 adults in the US and over 275,000 worldwide were diagnosed with oral cavity squamous cell carcinoma (OC-SCC). In the US alone >6,600 died from the disease in 2018. In addition to stage, perineural invasion, lymphovascular invasion, depth of invasion, and close or frankly positive resection margins are used to help stratify patients into low-, intermediate-, or high risk categories. Currently, all OC-SCC patients are treated primarily by surgical resection. Post-operative treatment depends on patient risk category. Low-risk patients receive surgery alone and studies have shown the benefit of PORT (Post-operative radiation therapy) in selected patients. A retrospective analysis of 1467 patients with low-risk OC-SCC where 740 (50.4%) received PORT had improved overall survival compared to 727 patients treated with surgery alone. Identifying these patients and better stratifying their risk of progression is critical. Meanwhile, patients with loco-regionally advanced (i.e. intermediate and high risk) disease are treated with PORT as standard. Select high risk patients may be treated with concomitant chemoradiation or subsequent chemotherapy. There is thus an urgent need to develop companion diagnostic tools to better define which patients will benefit from PORT, or, if intermediate or high risk, who will benefit from systemic therapy intensification. Recently, our group has developed a OC-SCC histomorphometric based image risk classifier (OHbIC) that uses computerized measurements of nuclear orientation, texture, shape, architecture from digital images of H&E-stained tumor sections to identify patients who are likely to recur versus those who are not. OHbIC was trained and validated on N=115 OC-SCC patients, and it had a 2 and 7-fold higher-correlation with disease specific survival compared to the 7th edition AJCC N- and T-stage (clinical variables used in patient prognosis). In this NIH R01, we seek to further improve the prognostic and predictive accuracy of OHbIC by incorporating new classes of image features relating to stromal morphology, pattern of invasion at the tumor leading edge, density and patterns of tumor infiltrating lymphocytes, and tumor cell multi-nucleation, features now recognized as potential histopathological markers of prognostic relevance in OC-SCC. Additionally, we seek to 1) validate OHbIC as prognostic of survival in clinically defined low-risk patients and identify those low-risk patients who would benefit from PORT and 2) validate OHbIC as not only prognostic of survival but also predictive of benefit from chemotherapeutic intensification for patients with loco-regionally advanced disease. This partnership will leverage long-standing collaborations in (1) digital pathomics from the Madabhushi group at Case Western Reserve, (2) surgical pathology and oncology expertise in oral cancer from Vanderbilt University, Cleveland Clinic, San Francisco VA, and Tata Memorial Centre, Mumbai to establish OHbIC as a tissue non-destructive and Affordable Precision Medicine (APM) solution for OC-SCC patients.

摘要：2018年，美国近34,000名成年人和全球超过275,000名成年人被诊断出患有口腔 鳞癌(OC-SCC)。仅在美国，2018年就有6600人死于这种疾病。除了舞台之外， 神经周围侵犯、淋巴血管侵犯、侵犯深度和切缘封闭或完全阳性 被用来帮助将患者分成低、中、高风险类别。目前，所有OC-SCC患者 主要通过手术切除来治疗。手术后的治疗取决于患者的风险类别。低风险 患者单独接受手术，研究表明PORT(术后放射治疗)的好处 在选定的患者中。1467例低危OC-SCC患者的回顾性分析，其中740例(50.4%) 与仅接受手术治疗的727名患者相比，PORT提高了总体存活率。确定这些 患者和更好地分层他们的进展风险是至关重要的。与此同时，地区性痴呆症患者 晚期(即中高风险)疾病以港口为标准进行治疗。选择高危患者 可同时进行放化疗或随后的化疗。因此，迫切需要 开发配套的诊断工具，以更好地定义哪些患者将受益于PORT，或者，如果是中级或 高风险，谁将受益于系统治疗的强化。 最近，我们小组开发了一种基于OC-SCC组织形态测量的图像风险分类器(OHbIC) 它使用计算机测量来自数字图像的原子核取向、纹理、形状和结构 H&E染色肿瘤切片，以确定哪些患者可能复发，哪些患者不复发。OHbIC是 对N=115名OC-SCC患者进行了培训和验证，其与疾病的相关性分别高出2倍和7倍 与第7版AJCC N期和T期(用于患者预后的临床变量)的特定生存期进行比较。 在这项NIH R01中，我们寻求通过结合以下方法进一步提高OHbIC的预后和预测准确性 新的图像特征与间质形态、肿瘤前沿的侵袭模式、 肿瘤浸润性淋巴细胞的密度和模式，以及肿瘤细胞的多核，现在公认的特征 作为预测OC-SCC预后的潜在组织病理学标志物。此外，我们寻求1)验证 OHbIC作为临床定义的低风险患者的生存预后，并确定哪些低风险患者 将受益于PORT和2)验证OHbIC不仅是生存的预后，而且是益处的预测 从局部地区晚期疾病患者的化疗强化。 这一合作伙伴关系将利用Madabhushi在(1)数字路径组学方面的长期合作 凯斯西部保护区小组，(2)范德比尔特口腔癌的外科病理学和肿瘤学专业知识 旧金山弗吉尼亚州克利夫兰诊所和孟买塔塔纪念中心将OHbIC建立为 用于OC-SCC患者的组织无损和负担得起的精密药物(APM)解决方案。