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转移性甲状腺癌对放射性碘治疗反应的建模:个性化医疗的概念验证研究

Modeling therapeutic response to radioiodine in metastatic thyroid cancer: a proof-of-concept study for individualized medicine.

作者信息

Barbolosi Dominique, Summer Ilyssa, Meille Christophe, Serre Raphaël, Kelly Antony, Zerdoud Slimane, Bournaud Claire, Schvartz Claire, Toubeau Michel, Toubert Marie-Elisabeth, Keller Isabelle, Taïeb David

机构信息

SMARTc Pharmacokinetics Unit, Aix-Marseille Université, Inserm S911 CRO2, Marseille, France.

Service de Médecine Nucléaire, Centre Jean Perrin, 63011 Clermont-Ferrand Cedex 01, France.

出版信息

Oncotarget. 2017 Jun 13;8(24):39167-39176. doi: 10.18632/oncotarget.16637.

Abstract

PURPOSE

Radioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions to maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach of this study was to build a mathematical model describing tumor growth with the kinetics of thyroglobulin (Tg) concentrations over time, following RAI for metastatic thyroid cancer.

EXPERIMENTAL DESIGN

Data from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model. A semi-mechanistic mathematical model that describes the tumor growth under RAI treatment was designed.

RESULTS

Our model was able to separate patients who responded to RAI from those who did not, concordant with the physicians' determination of therapeutic response. The estimated tumor doubling-time (Td was found to be the most informative parameter for the distinction between responders and non-responders. The model was also able to reclassify particular patients in early treatment stages.

CONCLUSIONS

The results of the model present classification criteria that could indicate whether patients will respond or not to RAI treatment, and provide the opportunity to perform personalized management plans.

摘要

目的

基于其摄取碘的能力,放射性碘治疗(RAI)传统上一直被用作转移性甲状腺癌的治疗方法。要在将毒性降至最低的同时使肿瘤反应最大化,必须认识到经验性试验存在无限可能性。因此,本研究的一种方法是建立一个数学模型,该模型根据转移性甲状腺癌放射性碘治疗后甲状腺球蛋白(Tg)浓度随时间的动力学来描述肿瘤生长。

实验设计

来自法国八个机构治疗的50例转移性乳头状甲状腺癌患者的数据被纳入该模型,这些患者在首次放射性碘治疗后随访了3年。设计了一个描述放射性碘治疗下肿瘤生长的半机制数学模型。

结果

我们的模型能够将对放射性碘治疗有反应的患者与无反应的患者区分开来,并与医生对治疗反应的判定结果一致。估计的肿瘤倍增时间(Td)被发现是区分反应者和无反应者最具信息量的参数。该模型还能够对早期治疗阶段的特定患者进行重新分类。

结论

该模型的结果提出了可表明患者是否会对放射性碘治疗产生反应的分类标准,并为制定个性化管理计划提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abe2/5503603/e24d1a474412/oncotarget-08-39167-g001.jpg

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