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

基本信息

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
项目类别：
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

项目摘要

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：2020 年，仅在美国就有超过 34,000 例 PCa 相关死亡。根治性治疗包括根治性前列腺切除术 (RP) 或放射治疗 (RT) 联合长期雄激素抑制治疗 (ADT)。这些已被证明是治疗器官局限性 PCa 的有效方法，并且已被证明可以降低 PCa 死亡风险。然而，在 38-52% 的病例中，病情已处于晚期且可能状况不佳预后可通过组织病理学发现。最近的一些临床试验显示了辅助治疗的益处特定 PCa 患者在 RP 或 RT 后的治疗。然而，确定哪些 PCa 患者遵循以下原则至关重要：根治性治疗（手术或放射）复发或转移的风险很高，因此将受益于辅助治疗与不会进行辅助治疗的患者相比，因此可以免除治疗的发病率和费用。认识到这一未满足的临床需求的重要性，2018 年 NCCN 前列腺癌指南修改为包括破译评分，这是一种基于分子基因的预后测试，用于确定以下情况的可能性：手术后转移。我们开发了自己的“综合风险评分”(IRiS) 图像分类器（npj Precison Onc，出版中14）结合了计算机从 H&E 组织中提取的形态腺体特征肿瘤的幻灯片。 IRiS 根据生化复发时间对 PCa 患者进行分层（N>900，6 个部位）（BCR）分为低风险组和高风险组（p<0.001；HR=2.44）。此外，IRiS 与术前 PSA 结合使用时在预测 N=173 名患者的 BCR 方面，Gleason 分级优于 Decipher（p<0.001；HR=3.23 vs HR=2.76）。在此 R01 中，我们将验证 IRiS 作为 (1) BCR 的预后和转移风险以及 (2) 预测确定性治疗（手术或放疗）后额外化疗的额外益处前列腺癌。在 Clin Cancer Res 最近发表的一篇论文中，我们确定了非裔美国人的 IRiS 特定预后特征 (AA) 患有 PCa 的男性。我们将在这些发现的基础上开发针对 PCa 的特定人群 IRiS 模型。我们将还通过包括 (1) 基质和筛状形态的特征，(2) 开发群体来进一步优化 IRiS 针对不同种族群体的特定 IRiS 模型，以及（3）用临床病理特征补充 IRiS。到验证 IRiS 可以预测辅助治疗的益处，我们需要访问随机临床试验组织切片涉及仅接受明确治疗（手术或 ADT+放射）和明确治疗的 PCa 患者的图像治疗+ 形容词化疗。 STAMPEDE 和 RTOG-0521 试验符合这些标准；我们已获得批准访问这些试验中的组织切片图像。为了使该工具广泛可用，IRiS 将集成到 PathPresenter，一个数字病理查看器和管理平台，目前在 178 个国家/地区使用。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 病理学和生物标志物专业知识克利夫兰诊所（Shilpa Gupta 博士）的医学肿瘤学专业知识将 IRiS 转化为第一个组织非针对 PCa 的破坏性预后和预测性平价精准医疗 (APM) 解决方案。