Integrating patient-specific clinical and biological factors towards individualizing utilization of proton and photon radiation therapy.
整合患者特定的临床和生物学因素,实现质子和光子放射治疗的个体化利用。
基本信息
- 批准号:10491819
- 负责人:
- 金额:$ 270.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-21 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AchievementAdvanced DevelopmentAffectBiologicalBiological FactorsBiological MarkersBiometryCancer CenterCharacteristicsClinicalClinical effectivenessComplicationCustomDataDevelopmentDoseEffectivenessEquilibriumEsophagusGeneral HospitalsGenomicsGenotypeGliomaGoalsHeterogeneityHumanImmune systemImmunologic FactorsImmunologicsImmunosuppressionIntensity modulated proton therapyJointsKnowledgeLiverLymphopeniaMalignant NeoplasmsMassachusettsMethodsModalityModelingNational Clinical Trials NetworkNormal tissue morphologyOncologyOutcomePatient SelectionPatient-Focused OutcomesPatientsPatternPhotonsPopulationPrediction of Response to TherapyProgram Research Project GrantsPropertyProton RadiationProtonsRadiationRadiation Dose UnitRadiation OncologyRadiation therapyRandomizedRelative Biological EffectivenessResearchResourcesRiskRisk FactorsRoleSelection for TreatmentsSideStatistical ModelsTechniquesTechnologyTherapeuticTherapy trialToxic effectUncertaintyadverse outcomebasecancer radiation therapycancer therapyclinical applicationcostdata managementdesigndosimetryfollow-upgenomic biomarkerimaging biomarkerimmunoregulationimprovedindividual patientpersonalized approachpopulation basedpotential biomarkerprecision medicinepredictive modelingprogramsproton beamproton therapyrandomized trialresponsetherapy designtreatment optimizationtumor
项目摘要
OVERALL - SUMMARY
This is a joint application for a program project grant by Massachusetts General Hospital and MD Anderson
Cancer Center. The progress we made in our most recent program projects (a P01 and a U19) has been criti-
cal to the clinical, physical, and biological aspects of proton therapy and its significance as an important cancer
treatment modality. The main achievements of the recently completed U19 (end date 8/31/20) were (1) the de-
velopment and activation of definitive esophagus, liver and glioma randomized proton vs. photon therapy trials
in cooperation with NRG, NCI and NCTN; (2) understanding and modeling the differences in response of nor-
mal tissues to highly disparate proton and photon dose distribution patterns; (3) understanding the complexities
of the biological effects of protons relative to photons; and (4) the development of advanced intensity modu-
lated proton therapy incorporating physical uncertainties and the variable biological effectiveness of protons.
Our research also revealed major gaps in the knowledge of the biological effects of protons, significant limita-
tions of the current population-based models of normal tissue and tumor response to protons vs. photons, and
uncertainty in the appropriateness of proton therapy in the face of heterogeneities in patient characteristics and
treatment techniques in unselected groups of patients. On the bright side, our research also discovered the
strong potential of proton therapy to reduce suppression of the immune system, which is commonly associated
with photon therapy and has been shown to lead to adverse outcomes. The overall goals of the proposed
P01 are (a) understanding relative clinical, biological and immunosuppressive effects of proton therapy vs.
photon therapy; (b) enhancing outcomes based on the physical, biological and immunological properties of
protons and photons; and (c) applying individualized (as opposed to population-based) approaches for the se-
lection of the optimum radiation modality for each patient and to enhance the potential for outcomes with the
use of radiation dose distributions tailored to the individual patient’s baseline and tumor characteristics. The
achievement of these goals will be carried out in three projects. Project 1: Understanding Normal Tissue Tox-
icity to Identify Patients Most Likely to Benefit from Proton vs. Photon Therapy; Project 2: Radiation-Induced
Lymphopenia (RIL): Understanding, Predictive Modeling and Developing Photon and Proton-Based Mitigation
Strategies; and Project 3: Investigating Enhanced Sensitivity of Tumors to Proton Beam Therapy: Mechanisms
and Biomarkers. The projects are highly integrated in that decisions regarding treatment modality selection,
treatment technique and optimization to maximally enhance the therapeutic ratio cannot be accomplished by
any one project alone. Such decisions must consider and balance normal tissue complications, tumor re-
sponse based on genotypic factors, and radiation-induced immunosuppression. The three projects will be sup-
ported by an Administrative Core and three resource cores: Core 1: Data Management and Computational
Support; Core 2: Translational Biospecimens and Imaging Biomarkers; and Core 3: Biostatistics.
总体-摘要
这是马萨诸塞州总医院和MD安德森联合申请的项目资助
癌症中心我们在最近的项目(P01和U19)中取得的进展至关重要,
质子治疗的临床,物理和生物学方面及其作为一种重要的癌症的意义
治疗方式最近完成的U19(结束日期8/31/20)的主要成就是(1)德-
确定性食管、肝脏和胶质瘤的清除和激活随机质子与光子治疗试验
与NRG,NCI和NCTN合作;(2)了解和模拟nor-
异常组织高度不同的质子和光子剂量分布模式;(3)理解复杂性
质子相对于光子的生物学效应;(4)先进的强度模块的发展,
结合物理不确定性和质子的可变生物有效性的延迟质子治疗。
我们的研究还揭示了质子生物学效应知识的主要空白,
当前基于人群的正常组织和肿瘤对质子与光子反应的模型,以及
质子治疗在患者特征异质性面前的适当性不确定性,
治疗技术在不同的患者群体。好的一面是,我们的研究还发现,
质子治疗减少免疫系统抑制的强大潜力,这通常与
光子疗法,并已被证明会导致不良后果。拟议的总体目标
P01是(a)了解质子治疗与
光子治疗;(B)基于光子的物理、生物和免疫学特性增强结果,
质子和光子;以及(c)采用个体化(而不是基于人口的)方法,
为每位患者选择最佳放射方式,并提高
使用根据个体患者的基线和肿瘤特征定制的辐射剂量分布。的
将通过三个项目实现这些目标。项目1:了解正常组织毒性-
识别最有可能从质子与光子治疗中获益的患者的能力;项目2:放射诱导
淋巴细胞减少症(RIL):理解,预测建模和开发基于光子和质子的缓解措施
项目3:研究肿瘤对质子束治疗的敏感性增强:机制
和生物标志物。这些项目是高度一体化的,因为关于治疗方式选择的决定,
治疗技术和优化,以最大限度地提高治疗率不能完成,
单独一个项目。这样的决定必须考虑和平衡正常组织并发症,肿瘤复发,
基于基因型因素的反应和辐射诱导的免疫抑制。这三个项目将在
由一个管理核心和三个资源核心移植:核心1:数据管理和计算
支持;核心2:转化生物标本和成像生物标志物;核心3:生物统计学。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Theodore S Hong其他文献
Emerging evidence-based role for external-beam radiation therapy in hepatocellular carcinoma
外束放疗在肝细胞癌中新兴的基于证据的作用
- DOI:
10.1016/s2468-1253(24)00267-x - 发表时间:
2025-04-01 - 期刊:
- 影响因子:38.600
- 作者:
Stephanie O Dudzinski;Neil B Newman;Jeff McIntyre;Reena Engineer;Nina N Sanford;Jennifer Y Wo;Jinsil Seong;Chandan Guha;Daniel T Chang;Theodore S Hong;Laura A Dawson;Eugene J Koay;Ethan B Ludmir - 通讯作者:
Ethan B Ludmir
Theodore S Hong的其他文献
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{{ truncateString('Theodore S Hong', 18)}}的其他基金
Integrating patient-specific clinical and biological factors towards individualizing utilization of proton and photon radiation therapy.
整合患者特定的临床和生物学因素,实现质子和光子放射治疗的个体化利用。
- 批准号:
10270304 - 财政年份:2021
- 资助金额:
$ 270.17万 - 项目类别:
Improving the Clinical Effectiveness and Understanding of the Biophysical Basis
提高临床有效性和对生物物理基础的理解
- 批准号:
9334068 - 财政年份:1997
- 资助金额:
$ 270.17万 - 项目类别:
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