Computational imaging approaches to personalized gastric cancer treatment

摘要 胃癌是全球主要的疾病负担，也是全球癌症死亡的主要原因。 目前的治疗决定主要是根据分期做出的，分期将患者分为 几个预后组。对于局部和局部晚期疾病患者， 手术加化疗是标准治疗方法。然而，生存结果差异很大，甚至 在同一阶段的患者中。某些患有早期疾病的患者 复发风险足够低，可能不会受益于，甚至可能受到伤害， 考虑到化疗的毒副作用。相反，许多患者 侵袭性肿瘤对标准化疗反应不佳，尽管接受了化疗， 广泛但无效的治疗。因此，目前一刀切的做法是次优的， 导致许多患者的过度治疗和治疗不足。对可靠的预后评估的需求尚未得到满足。 和预测模型来指导胃癌的个性化治疗。为了解决这一未满足的需求， 我们提出了肿瘤形态和空间异质性的强大放射组学特征，并建立了 其预后价值。此外，我们将把病理生物学知识纳入设计， 用于预测预后的深度学习模型。此外，我们将开发新的深度学习， 分析纵向图像以预测对新辅助治疗的病理反应。 最后，通过利用影像学数据的互补价值，临床病理变量和序列 血清标志物，我们将构建综合模型，以进一步提高预测。如果成功， 提出的模型将在两个方面有用：（1），识别哪些早期胃癌患者可能 安全放弃化疗，避免毒副反应;（2）选择最有效的化疗方案 对于一个特定的病人。此外，该模型还可以识别患有晚期疾病的患者， 对标准化疗有反应，并可能受益于新的靶向治疗或免疫治疗。 所提出的计算成像方法一般适用于响应监测 和疾病监测。最后，基于AI的成像技术 在这里发展可以为少数群体和社区中得不到充分服务的人口带来好处 设置.在胃癌方面取得的进展不仅将改善美国患者的预后， 由于其在世界范围内的高发病率和死亡率，也具有全球影响。

ABSTRACT Gastric cancer is a major global disease burden and leading cause of cancer mortality worldwide. Current treatment decision is made primarily on the basis of staging, which divides patients into several prognostic groups. For patients with localized and locally advanced disease, curative-intent surgery with chemotherapy is the standard treatment. However, survival outcomes vary widely, even among patients with disease of the same stage. Certain patients with early-stage disease have a sufficiently low risk of recurrence and may not benefit from, or could even be harmed by, chemotherapy given the associated toxicity and side effects. Conversely, many patients with aggressive tumors do not respond well to standard chemotherapy and still recur despite receiving extensive but ineffective treatment. Therefore, current one-size-fits-all approach is suboptimal, leading to over- and under-treatment in many patients. There is an unmet need for reliable prognostic and predictive models to guide personalized treatment of gastric cancer. To address this unmet need, we propose robust radiomics features of tumor morphology and spatial heterogeneity and establish their prognostic value. In addition, we will incorporate pathobiological knowledge into the design of deep learning models for predicting prognosis. Further, we will develop novel deep learning architecture to analyze longitudinal images for predicting pathologic response to neoadjuvant therapy. Finally, by leveraging the complementary value of imaging data, clinicopathologic variables and serial serum markers, we will construct integrative models to further improve prediction. If successful, the proposed models will be useful in two ways: (1), identify which patients with early gastric cancer may safely forego chemotherapy and avoid toxicity; (2), select the most effective chemotherapy regimen for a given patient. Further, the models can also identify patients with advanced disease who do not respond to standard chemotherapy and may benefit from novel targeted therapy or immunotherapy. The proposed computational imaging approaches are generally applicable for response monitoring and disease surveillance in many solid tumor types. Finally, the AI-based imaging technology developed here can bring benefit to underserved populations in minority groups and community settings. Progress made in gastric cancer will not only improve outcomes for patients in the US but also have global impact given its high incidence and mortality worldwide.