Optimizing the Treatment of Pancreatic Adenocarcinoma

项目概要/摘要： 本研究的最终目的是改善胰腺导管腺癌（PDAC）患者的预后。 生存率和人口死亡率。虽然随着时间的推移，许多癌症的生存率有所提高， PDAC占所有胰腺癌的绝大多数（90%），仍然很差。这部分是 因为大多数PDAC是在其病程晚期发现的，此时手术切除是不可能的。 然而，即使在可切除的原发性肿瘤的病例中，由于早期转移， 通常是微观的和不可检测的。来自非常小的肿瘤的早期转移是转移的关键障碍。 提高胰腺癌死亡率。系统化疗可以治疗早期看不见的微转移 PDAC，因此当用作辅助或新辅助时，有可能改善患者结局 治疗结合手术切除和放射治疗。目前只有约20%的确诊病例 PDAC在诊断时可手术切除;然而，有希望的新化疗方案， 当与放疗结合作为新辅助治疗时，可能使许多肿瘤的最终切除成为可能。 PDAC（30%），目前处于可切除边缘或局部晚期。如果证明有效，这些新的治疗方法 这些策略可能是改善PDAC生存率的重要一步， 达到大多数诊断为PDAC的患者。然而，如何最好地应用 新辅助和辅助治疗方案，具有相当大的毒性。必须注意 将临床试验的结果应用于大部分诊断为PDAC的老年患者， 和比试验参与者更不健康（合并症）。在这样的场景中， 对于临床试验数据的普遍性，建模方法可以起到补充作用。的疾病 PDAC仿真模型可以提供一个框架来综合和整合各种肿瘤和患者 因此，可以全面平衡治疗计划的潜在益处和危害。 该研究计划将建立在我们的多元化团队先前和正在进行的工作基础上， 建模师、人口科学家、癌症生物学家和在PDAC各方面都有经验的临床医生 管理和治疗。我们的计划是开发一个全面的PDAC治疗模型， 分析以提供见解：改善早期PDAC患者的总生存期，提高决策 制定个性化治疗计划，优化资源利用，优先考虑并告知未来 研究和试验。该项目的目标将是：目标1-完善和验证PDAC模型，重点是 治疗;目标2-根据个体患者的特点设计个性化的治疗策略， 优化早期PDAC的治疗;目标3-确定新的个性化治疗策略的影响 人口死亡率。

Project Summary/Abstract: The ultimate goal of the proposed research is to improve pancreatic ductal adenocarcinoma (PDAC) patient survival and population mortality. While survival for many cancers has improved over time, the survival for PDAC, which constitutes the vast majority (90%) of all cancers of the pancreas, remains poor. This is in part because the majority of PDACs are detected late in their course when surgical resection is not possible. However, even in cases with a resectable primary tumor, cure remains elusive because of early metastases, which are frequently microscopic and undetectable. Early metastasis from very small tumors is a key barrier to improving pancreatic cancer mortality. Systematic chemotherapy can treat unseen micrometastases in early PDAC and thus has the potential to improve patient outcomes when used as an adjuvant or neoadjuvant therapy in conjunction with surgical resection and radiotherapy. At present only about 20% of diagnosed PDACs are surgically resectable at the time of diagnosis; however, promising newer chemotherapy regimens, when combined with radiotherapy as neoadjuvant treatment, may enable the definitive resection of many PDACs (30%) that are now borderline resectable or locally advanced. If proven effective, these new treatment strategies potentially represent a major step toward improving PDAC survival and may bring a cure within reach for the majority of patients diagnosed with PDAC. Yet, questions remain about how best to apply neoadjuvant and adjuvant therapy regimens, which have considerable toxicities. Care must be taken in applying the results of clinical trials to a significant proportion of patients diagnosed with PDAC, who are older and less healthy (comorbidities) than trial participants. In scenarios such as these, where there are limitations to the generalizability of clinical trial data, modeling approaches can serve a complementary role. A disease simulation model of PDAC can provide a framework to synthesize and incorporate various tumor and patient factors thereby allowing for a comprehensive balancing of the potential benefits and harms of treatment plans. The research plan will build upon prior and ongoing work by our diverse team, comprised of mathematical modelers, population scientists, cancer biologists, and clinicians with experience in all aspects of PDAC management and treatment. Our plan is to develop a comprehensive PDAC treatment model that will be analyzed to provide insights to: improve overall survival of patients with early stage PDAC, enhance decision making regarding personalized treatment plans, optimize resource utilization, and prioritize and inform future research and trials. The aims of the project will be: Aim 1-Refine and validate a model of PDAC focused on treatment; Aim 2-Design personalized treatment strategies tailored to individual patient characteristics to optimize treatment of early PDAC; Aim 3-Determine the impact of the new personalized treatment strategies on population mortality.