Genetic testing to guide pediatric cancer care and follow up: using anthracycline-associated cardiac toxicity as a model for the future
基因检测指导儿科癌症护理和随访:使用蒽环类药物相关的心脏毒性作为未来的模型
基本信息
- 批准号:9789024
- 负责人:
- 金额:$ 40.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-19 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAftercareAmerican Society of Clinical OncologyAnnual ReportsAnthracyclinesBenefits and RisksCancer ControlCancer ModelCancer PatientCancer SurvivorCardiacCardiac DeathCardiotoxicityCaringChestChildChild CareChildhoodChildhood Cancer Survivor StudyChildhood Cancer TreatmentClinicalClinical Course of DiseaseClinical DataClinical ResearchCohort StudiesCongestive Heart FailureDataDiagnosisDiseaseDoseEpidemiologyExcess MortalityFutureGeneticGenetic MarkersGenetic Predisposition to DiseaseGenetic RiskGenetic screening methodGenomicsGenotypeHealthHeart DiseasesIndividualLife ExpectancyMalignant Childhood NeoplasmMalignant NeoplasmsMedical GeneticsMethodsModelingMorbidity - disease rateNatureOutcomePatientsPediatric OncologyPediatric Oncology GroupPenetrancePredispositionPrevalencePublishingQuality of lifeRadiation therapyRandomized Clinical TrialsRecommendationResearchResourcesRiskRisk FactorsRisk MarkerSaint Jude Children&aposs Research HospitalSourceStatistical MethodsSubgroupSurvival RateSurvivorsTestingTimeToxic effectTranslatingTreatment-related toxicityUncertaintyWorkadverse outcomeanticancer researchbasecancer carecancer diagnosiscancer genomicscancer therapycare outcomeschildhood cancer survivorclinical careclinical practiceclinical riskcohortcostdisorder controlevidence baseflexibilityfollow-upgenetic informationgenetic risk assessmentgenetic risk factorgenetic varianthigh riskimprovedimproved outcomeindividualized medicinemodels and simulationmortality risknovelnovel strategiespersonalized carepersonalized medicinepersonalized strategiesprecision medicinepredictive modelingprematureprospectivescreening guidelinestreatment risk
项目摘要
PROJECT SUMMARY/ABSTRACT
Recent genomic advances have identified a potential for germline risk markers to predict risk of treatment-
related toxicity in children treated for cancer. Although advances in pediatric cancer treatment have led to
remarkable increases in survival rates, long-term morbidity and early mortality risks underscore the need for
new approaches that minimize late toxicities while maintaining disease control; using genetic markers to
predict risk and change therapy represents a potential strategy to reduce adverse outcomes. Genetic risk
assessment has created great excitement about the possibility of individualized therapy adapted for patients
who carry increased or decreased risk. For example, research in cancer survivor cohorts have demonstrated a
five-fold increased risk of congestive heart failure and a seven-fold increased risk of premature cardiac death.
Clinical practice recommendations have recently been published for individualized adaptation of treatment and
surveillance based upon genetic cardiac-risk profile in childhood cancer patients receiving anthracycline
therapy. However, considerable uncertainty surrounds how successfully genetic information may translate into
improved care and outcomes for children with cancer. Further, the rarity of childhood cancer and the long
latency needed to observe late outcomes limit the feasibility of prospective trials to evaluate a precision-
medicine approach to care and follow-up. We propose to employ a decision-analytic modeling approach to
determine how genetic testing may inform clinical care, both of initial cancer therapy and post-treatment care
based on individual susceptibility for cardiotoxicity. We will develop a novel, flexible microsimulation model of
the clinical course of childhood cancer to project the full spectrum of health outcomes relevant to the childhood
cancer, including initial disease control and treatment-related late toxicities, and then incorporate genetic data
to assess the impact upon these outcomes. This modeling framework will integrate data from multiple
resources, including the Childhood Cancer Survivors Study (CCSS) to (1) project long-term outcomes for
children diagnosed with cancer; (2) determine the clinical impact of utilizing genetic variant testing for
cardiotoxicity in guiding cancer care; and (3) assess how consideration of genetic markers can improve follow-
up cardiac screening recommendations for at-risk survivors. We aim to portray the scope and nature of the
uncertainties that surround model parameters and their impact on modeled outcomes by employing
bootstrapping methods, statistical methods to extrapolate cardiotoxicity risks, and rigorous approaches to
uncertainty analysis. By uniquely leveraging the CCSS data to characterize the lifelong treatment-related
cardiotoxicity risks, our proposed research will establish a novel analytic framework for evaluating the
uncertainties and tradeoffs surrounding the use of genetic testing in pediatric oncology, and form the basis for
understanding the impact of genetic risk testing for other toxicities.
项目概要/摘要
最近的基因组进展已经确定了种系风险标记物预测治疗风险的潜力 -
接受癌症治疗的儿童中的相关毒性。尽管小儿癌症治疗的进步已导致
生存率、长期发病率和早期死亡风险的显着增加凸显了需要
在保持疾病控制的同时最大限度地减少后期毒性的新方法;使用遗传标记
预测风险并改变治疗是减少不良后果的潜在策略。遗传风险
评估使人们对适合患者的个体化治疗的可能性感到非常兴奋
风险增加或减少的人。例如,对癌症幸存者队列的研究表明
充血性心力衰竭的风险增加五倍,心源性过早死亡的风险增加七倍。
最近发布了针对个体化治疗和调整的临床实践建议
基于接受蒽环类药物的儿童癌症患者的遗传心脏风险概况的监测
治疗。然而,遗传信息如何成功转化为基因信息还存在相当大的不确定性。
改善癌症儿童的护理和治疗结果。此外,儿童癌症的罕见性和长期
观察后期结果所需的延迟限制了评估精确度的前瞻性试验的可行性
医学方法进行护理和随访。我们建议采用决策分析建模方法
确定基因检测如何为临床护理(包括初始癌症治疗和治疗后护理)提供信息
基于个体对心脏毒性的易感性。我们将开发一种新颖、灵活的微观模拟模型
儿童癌症的临床过程,以预测与儿童相关的全方位健康结果
癌症,包括初始疾病控制和治疗相关的晚期毒性,然后纳入遗传数据
评估对这些结果的影响。该建模框架将集成来自多个
资源,包括儿童癌症幸存者研究 (CCSS),以 (1) 预测长期结果
被诊断患有癌症的儿童; (2) 确定利用遗传变异检测的临床影响
指导癌症治疗中的心脏毒性; (3) 评估考虑遗传标记如何改善随访
为高危幸存者提供心脏筛查建议。我们的目标是描绘该项目的范围和性质
围绕模型参数的不确定性及其对建模结果的影响
引导方法、推断心脏毒性风险的统计方法以及严格的方法
不确定性分析。通过独特地利用 CCSS 数据来描述与终生治疗相关的特征
心脏毒性风险,我们提出的研究将建立一个新的分析框架来评估
围绕儿科肿瘤学中使用基因检测的不确定性和权衡,并构成了基础
了解遗传风险测试对其他毒性的影响。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)
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Jennifer M. Yeh其他文献
Jennifer M. Yeh的其他文献
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{{ truncateString('Jennifer M. Yeh', 18)}}的其他基金
Can risk-reducing medications improve breast cancer prevention in childhood and adolescent cancer survivors? Comparative modeling to inform care
降低风险的药物可以改善儿童和青少年癌症幸存者的乳腺癌预防吗?
- 批准号:
10459788 - 财政年份:2022
- 资助金额:
$ 40.34万 - 项目类别:
Can risk-reducing medications improve breast cancer prevention in childhood and adolescent cancer survivors? Comparative modeling to inform care
降低风险的药物可以改善儿童和青少年癌症幸存者的乳腺癌预防吗?
- 批准号:
10675772 - 财政年份:2022
- 资助金额:
$ 40.34万 - 项目类别:
Genetic testing to guide pediatric cancer care and follow up: using anthracycline-associated cardiac toxicity as a model for the future
基因检测指导儿科癌症护理和随访:使用蒽环类药物相关的心脏毒性作为未来的模型
- 批准号:
10231094 - 财政年份:2018
- 资助金额:
$ 40.34万 - 项目类别:
Gastric Cancer Prevention: Evaluating U.S. Risk Factor Trends and New Technology
胃癌预防:评估美国危险因素趋势和新技术
- 批准号:
8522167 - 财政年份:2010
- 资助金额:
$ 40.34万 - 项目类别:
Gastric Cancer Prevention: Evaluating U.S. Risk Factor Trends and New Technology
胃癌预防:评估美国危险因素趋势和新技术
- 批准号:
8133736 - 财政年份:2010
- 资助金额:
$ 40.34万 - 项目类别:
Gastric Cancer Prevention: Evaluating U.S. Risk Factor Trends and New Technology
胃癌预防:评估美国危险因素趋势和新技术
- 批准号:
8298248 - 财政年份:2010
- 资助金额:
$ 40.34万 - 项目类别:
Gastric Cancer Prevention: Evaluating U.S. Risk Factor Trends and New Technology
胃癌预防:评估美国危险因素趋势和新技术
- 批准号:
8706073 - 财政年份:2010
- 资助金额:
$ 40.34万 - 项目类别:
Gastric Cancer Prevention: Evaluating U.S. Risk Factor Trends and New Technology
胃癌预防:评估美国危险因素趋势和新技术
- 批准号:
7989369 - 财政年份:2010
- 资助金额:
$ 40.34万 - 项目类别:
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