Prognostic and Predictive Digital Tissue Image Assay for Prostate Cancer

前列腺癌的预后和预测数字组织图像分析

• 批准号: 10697304
• 负责人: Shilpa Gupta
• 金额: $ 62.76万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-05 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697304
• 关键词: Accounting; Adjuvant Therapy; African American; Androgen Suppression; Architecture; Biochemical; Biological Assay; Biological Markers; Biopsy; Biopsy Specimen; Cancer Patient; Cell Nucleus; Cessation of life; Clinic; Clinical; Clinical Trials; Collagen; Collagen Fiber; Complement; Computer software; Computers; Country; Cues; Data; Dedications; Ethnic Population; Exhibits; Genomics; Gland; Gleason Grade for Prostate Cancer; Goals; Guidelines; Habitats; Image; Image-Guided Surgery; Malignant Neoplasms; Malignant neoplasm of prostate; Medical Oncology; Modeling; Molecular; Morbidity - disease rate; Morphology; National Comprehensive Cancer Network; Neoplasm Metastasis; Nomograms; Nuclear; Oncology; Operative Surgical Procedures; Organ; Outcome; Paper; Pathologic; Pathology; Patients; Pattern; Pennsylvania; Performance; Phenotype; Population; Prognosis; Prostate Cancer therapy; Publishing; Radiation; Radiation Therapy Oncology Group; Radiation therapy; Radical Prostatectomy; Recurrence; Recurrent Malignant Neoplasm; Risk; Risk Reduction; Secure; Site; Slide; Specimen; Testing; Time; Tissue imaging; Tissues; Translating; Tumor Tissue; Universities; Validation; Visual; advanced disease; androgen deprivation therapy; cancer recurrence; caucasian American; chemotherapy; companion diagnostics; computerized; cost; diagnostic assay; digital; digital imaging; digital pathology; disorder risk; effective therapy; follow-up; genetic testing; hazard; head-to-head comparison; high risk; high risk population; improved; indexing; innovation; men; mortality risk; precision medicine; precision oncology; predictive test; prognostic; prognostic assays; prostate cancer model; prostate cancer risk; prototype; randomized, clinical trials; risk minimization; success; tool; treatment guidelines; tumor

PROJECT SUMMARY: There were >34,000 PCa-related deaths in 2020 in the US alone. Definitive treatment includes Radical prostatectomy (RP) or radiotherapy (RT) with long term androgen-suppression therapy (ADT). These have been shown to be effective treatments for organ-confined PCa and have been demonstrated to reduce the risk of death from PCa. In 38-52% of cases, however, advanced disease with potentially poor prognosis is found on tissue pathology. A number of recent clinical trials have shown the benefit of adjuvant therapy in select PCa patients post-RP or RT. However, it is critical to identify those PCa patients who following definitive therapy (surgery or radiation) are at high-risk for recurrence or metastasis and thus will benefit from adjuvant therapy versus patients who will not and hence may be spared the morbidity and cost of therapy. Recognizing the significance of this unmet clinical need, in 2018 the NCCN guidelines for PCa were modified to include the Decipher Score, a prognostic molecular gene-based test to identify the likelihood of metastasis following surgery. We have developed our own "Integrated Risk Score" (IRiS) image classifier that (npj Precison Onc, In Press14) combines computer extracted morphologic glandular features from H&E tissue slides of the tumor. IRiS stratified PCa patients (N>900, 6 sites) based on their time to biochemical recurrence (BCR) into low- and high-risk groups (p<0.001; HR=2.44). Further, IRiS when combined with pre-op PSA and Gleason grade outperformed Decipher in predicting BCR in N=173 patients (p<0.001; HR=3.23 vs HR=2.76). In this R01, we will validate IRiS as (1) prognostic of BCR and risk of metastasis as well as (2) predictive of the added benefit of additional chemotherapy following definitive therapy (surgery or radiation) in PCa. In a recent paper in Clin Cancer Res, we identified IRiS specific prognostic features for African American (AA) men with PCa. We will build on these findings to develop population specific IRiS models for PCa. We will also further optimize IRiS by including (1) features of stromal and cribriform morphology, (2) develop population specific IRiS models for different ethnic groups, and (3) complement IRiS with clinico-pathological features. To validate IRiS as predictive of benefit of adjuvant therapy, we need access to randomized clinical trial tissue slide images involving PCa patients treated with definitive therapy alone (surgery or ADT+radiation) and definitive therapy+ adj. chemo. The STAMPEDE and RTOG-0521 trials fit these criteria; we have secured approval to access tissue slide images from these trials. To make the tool widely available, IRiS will be integrated into PathPresenter, a digital pathology viewer and management platform currently in use in 178 countries. This partnership will combine expertise in (a) computational pathology of the Madabhushi group, (2) clinical, pathological and biomarker expertise of PCa from the University of Pennsylvania (Drs. Priti Lal) and (3) GU medical oncology expertise from the Cleveland Clinic (Dr Shilpa Gupta) to translate IRiS as the first tissue non- destructive prognostic and predictive Affordable Precision Medicine (APM) solution for PCa.

项目摘要：仅在美国，2020年就有34,000例与PCA相关的死亡。明确的治疗 包括根治性前列腺切除术(RP)或放射治疗(RT)加长期雄激素抑制疗法(ADT)。 这些已被证明是治疗器官受限的前列腺癌的有效方法，并已被证明 降低自控镇痛的死亡风险。然而，在38%-52%的病例中，晚期疾病潜在地很差 预后取决于组织病理学。最近的一些临床试验显示了佐剂的益处。 选择的前列腺癌患者在RP或RT后的治疗。然而，关键是要确定那些遵循以下原则的PCA患者 明确的治疗(手术或放射治疗)具有复发或转移的高风险，因此将受益于 辅助治疗与不愿接受治疗的患者相比，可能会避免发病率和治疗费用。 认识到这一未得到满足的临床需求的重要性，2018年NCCN关于PCA的指南是 修改后包括解密评分，这是一种基于分子基因的预后测试，以确定 手术后的转移。我们已经开发了我们自己的“综合风险评分”(IRIS)图像分类器 (NPJ Precison ONC，in Press 14)结合了计算机从H&E组织中提取的腺体形态特征 肿瘤的玻片。基于生化复发时间的虹膜分层PCa患者(N&gT；900，6个部位) (Bcr)分为低风险组和高风险组(p&lt；0.001；HR=2.44)。此外，当虹膜与术前PSA和 在N=173例患者中，Gleason分级对BCR的预测优于Decpher(P&lt；0.001；HR=3.23vsHR=2.76)。 在这个R01中，我们将验证虹膜作为(1)bcr和转移风险的预后以及(2) 预测明确治疗(手术或放射治疗)后额外化疗的额外益处 PCA。在最近发表在《临床癌症研究》杂志上的一篇论文中，我们确定了非裔美国人虹膜的特殊预后特征 (Aa)患有前列腺癌的男性。我们将在这些发现的基础上开发用于PCA的特定于人群的虹膜模型。我们会 还进一步优化虹膜，包括(1)基质和筛状形态特征，(2)发展种群 针对不同民族的虹膜模型；(3)虹膜临床病理特征的补充。至 验证虹膜作为辅助治疗益处的预测，我们需要获得随机临床试验组织切片 涉及单独接受明确治疗(手术或ADT+放射治疗)和明确治疗的PCA患者的图像 治疗+；治疗化疗。踩踏事件和RTOG-0521试验符合这些标准；我们已获得批准 获取这些试验的组织切片图像。为了使该工具广泛可用，Iris将集成到 PathPresenter，一个目前在178个国家和地区使用的数字病理查看和管理平台。这 合作伙伴关系将结合(A)Madabhushi小组的计算病理学，(2)临床， 宾夕法尼亚大学Priti Lal博士和(3)Gu的PCA的病理和生物标记物专业知识 来自克利夫兰诊所的医学肿瘤学专业知识(希尔帕·古普塔博士)将虹膜翻译为第一个非 用于PCa的破坏性预测和可负担得起的精准医学(APM)解决方案。