Optimal screening and surveillance regimes for early diagnosis of cancer and precision medicine using mathematical modelling

使用数学模型进行癌症早期诊断和精准医疗的最佳筛查和监测制度

基本信息

  • 批准号:
    MR/S003851/1
  • 负责人:
  • 金额:
    $ 35.87万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Fellowship
  • 财政年份:
    2018
  • 资助国家:
    英国
  • 起止时间:
    2018 至 无数据
  • 项目状态:
    已结题

项目摘要

The main rationale for cancer screening is that detecting disease early offers the opportunity to change its prognosis. Compared with symptomatic cancers, the lifetime prognosis is often greatly improved for patients found to have precancerous lesions or small cancers that are detected at an early stage. Therefore, clinicians focus on identifying patients with precancerous change on initial tests (screens), and then after this initial screening may advise these patients to undergo long-term, periodic screening by returning to the clinic at certain intervals for regular examinations (surveillance screens) throughout the course of their lives. However, many precancerous changes will never progress to cancer in the lifetime of the patient. Thus, many patients who undergo regular surveillance will never be diagnosed with cancer in their lifetimes. Overall, many current approaches for prevention by screening and surveillance programs have achieved minimal success in reducing cancer deaths at a high cost to healthcare services, and thus paradoxically yield both under-diagnosis due to inadequate screening and over-diagnosis due to ineffective patient stratification in surveillance protocols. Herein lies the balancing act performed during risk stratification - identify who is most `at risk' of progressing to cancer and suggest effective surveillance and intervention strategies for the high risk groups. With this motivation, the overall public health goal of the mathematical modelling presented in this research plan is to help improve the efficacy of screening and surveillance for precancerous and cancer lesions. Although clinical endpoints like cancer incidence and prevalence of pre-cancerous change are reported on a population level, many important biological processes on smaller physical and temporal scales occur with significant differences between patients during disease progression from normal tissue to incident cancer. Due to the biological and clinical nature of screening patients at various times during their lives, such details at tissue and cell levels provide vital information to determine screening outcomes obtained by different modalities and protocols. This research plan will use many such levels of data in inventive and rigorous ways to improve personalized healthcare. Within the MRC priority area Precision Medicine and Diagnostics, mathematical modelling of cancer formation can be used to derive and to optimise the timing of clinical screens so that an individual is screened within a certain "window of opportunity" for intervention when early cancer development may be observed. By using data from epidemiological studies with long-term patient follow-up, current empirical approaches can aid in screening design and may inform cost-effectiveness analyses to compare proposed screening and intervention strategies. However, mechanistic modelling that incorporates a greater level of biological understanding and detail for how and when normal tissues progress to cancer can be used for a more refined screening design than typically implemented in population screening studies.The aims of this Health Data Research UK research plan are1) To use mathematical modelling to inform optimal cancer screening recommendations for a population,2) To perform patient risk stratification by identifying who is low risk versus who is high risk in order to make personalised surveillance regimes that are more effective than "one-size-fits-all" approaches, 3) To build tools that will assist in precision medicine such as clearly portraying future cancer risk to a patient in visuals aids.
癌症筛查的主要原理是早期发现疾病提供了改变其预后的机会。与有症状的癌症相比,发现癌前病变或早期发现的小癌症患者的终生预后往往大大改善。因此,临床医生的重点是在初始检查(筛查)中识别癌前病变患者,然后在初始筛查之后,可能会建议这些患者在其一生中每隔一定时间返回诊所进行定期检查(监测筛查),进行长期的定期筛查。然而,许多癌前病变在患者的一生中永远不会发展成癌症。因此,许多接受定期监测的患者在其一生中永远不会被诊断出患有癌症。总的来说,目前许多通过筛查和监测项目进行预防的方法在降低癌症死亡率方面取得了很小的成功,但却给医疗服务带来了高昂的成本,因此矛盾的是,由于筛查不足而导致诊断不足,而由于监测方案中无效的患者分层而导致过度诊断。这就是在风险分层过程中进行的平衡行为——确定谁是最“有风险”发展为癌症的人,并为高风险群体提出有效的监测和干预策略。基于这一动机,本研究计划中提出的数学模型的总体公共卫生目标是帮助提高癌前病变和癌症病变的筛查和监测效果。虽然临床终点如癌症发病率和癌前改变的流行率是在人群水平上报道的,但在从正常组织到偶发癌症的疾病进展过程中,患者之间发生的许多重要的生理和时间尺度的生物学过程存在显著差异。由于在患者生命的不同时期进行筛查的生物学和临床性质,这些组织和细胞水平的细节为确定通过不同方式和方案获得的筛查结果提供了重要信息。该研究计划将以创造性和严格的方式使用许多此类级别的数据来改进个性化医疗保健。在MRC的重点领域精准医学和诊断中,癌症形成的数学模型可以用来得出和优化临床筛查的时间,以便在观察到早期癌症发展时,在特定的“机会之窗”内对个体进行筛查,进行干预。通过使用流行病学研究和长期患者随访的数据,目前的经验方法可以帮助筛查设计,并可以为成本效益分析提供信息,以比较拟议的筛查和干预策略。然而,结合更高水平的生物学理解和正常组织如何以及何时进展为癌症的细节的机制建模可以用于比通常在人群筛查研究中实施的更精细的筛查设计。这项英国健康数据研究计划的目的是:1)使用数学模型为人群提供最佳的癌症筛查建议;2)通过确定谁是低风险,谁是高风险,对患者进行风险分层,以便制定比“一刀切”方法更有效的个性化监测制度。3)建立有助于精准医疗的工具,例如在视觉辅助工具中清晰地向患者描绘未来的癌症风险。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Barrett's esophagus is the precursor of all esophageal adenocarcinomas
巴雷特食管是所有食管腺癌的先兆
  • DOI:
    10.1101/2020.05.14.096826
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Curtius K
  • 通讯作者:
    Curtius K
Computational modelling suggests that Barrett's oesophagus may be the precursor of all oesophageal adenocarcinomas.
  • DOI:
    10.1136/gutjnl-2020-321598
  • 发表时间:
    2020-11-24
  • 期刊:
  • 影响因子:
    24.5
  • 作者:
    Curtius K;Rubenstein JH;Chak A;Inadomi JM
  • 通讯作者:
    Inadomi JM
From Colitis to Cancer: An Evolutionary Trajectory That Merges Maths and Biology.
  • DOI:
    10.3389/fimmu.2018.02368
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    7.3
  • 作者:
    Al Bakir I;Curtius K;Graham TA
  • 通讯作者:
    Graham TA
Implications of Epigenetic Drift in Colorectal Neoplasia.
  • DOI:
    10.1158/0008-5472.can-18-1682
  • 发表时间:
    2019-02-01
  • 期刊:
  • 影响因子:
    11.2
  • 作者:
    Luebeck GE;Hazelton WD;Curtius K;Maden SK;Yu M;Carter KT;Burke W;Lampe PD;Li CI;Ulrich CM;Newcomb PA;Westerhoff M;Kaz AM;Luo Y;Inadomi JM;Grady WM
  • 通讯作者:
    Grady WM
Evolutionary history of human colitis-associated colorectal cancer.
  • DOI:
    10.1136/gutjnl-2018-316191
  • 发表时间:
    2019-06
  • 期刊:
  • 影响因子:
    24.5
  • 作者:
    Baker AM;Cross W;Curtius K;Al Bakir I;Choi CR;Davis HL;Temko D;Biswas S;Martinez P;Williams MJ;Lindsay JO;Feakins R;Vega R;Hayes SJ;Tomlinson IPM;McDonald SAC;Moorghen M;Silver A;East JE;Wright NA;Wang LM;Rodriguez-Justo M;Jansen M;Hart AL;Leedham SJ;Graham TA
  • 通讯作者:
    Graham TA
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Kathleen Curtius其他文献

Mechanisms of Chromosomal Instability in High-grade Serous Ovarian Carcinoma
高级别浆液性卵巢癌染色体不稳定性的机制
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Naoka Tamura;Nadeem Shaikh;Daniel Muliaditan;Jennifer R. McGuinness;D. Moralli;Mary;C. Green;D. Bowtell;D. Bowtell;F. Balkwill;Kathleen Curtius;S. McClelland
  • 通讯作者:
    S. McClelland

Kathleen Curtius的其他文献

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