Comput Math Methods Med - Modeling the spatial distribution of chronic tumor hypoxia: implications for experimental and clinical studies.


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Tumor oxygenation status is considered one of the important prognostic markers in cancer since it strongly influences the response of cancer cells to various treatments; in particular, to radiation therapy. Thus, a proper and accurate assessment of tumor oxygen distribution before the treatment may highly affect the outcome of the treatment. The heterogeneous nature of tumor hypoxia, mainly influenced by the complex tumor microenvironment, often makes its quantification very difficult. The usual methods used to measure tumor hypoxia are biomarkers and the polarographic needle electrode. Although these techniques may provide an acceptable assessment of hypoxia, they are invasive and may not always give a spatial distribution of hypoxia, which is very useful for treatment planning. An alternative method to quantify the tumor hypoxia is to use theoretical simulations with the knowledge of tumor vasculature. The purpose of this paper is to model tumor hypoxia using a known spatial distribution of tumor vasculature obtained from image data, to analyze the accuracy of polarographic needle electrode measurements in quantifying hypoxia, to quantify the optimum number of measurements required to satisfactorily evaluate the tumor oxygenation status, and to study the effects of hypoxia on radiation response. Our results indicate that the model successfully generated an accurate oxygenation map for tumor cross-sections with known vascular distribution. The method developed here provides a way to estimate tumor hypoxia and provides guidance in planning accurate and effective therapeutic strategies and invasive estimation techniques. Our results agree with the previous findings that the needle electrode technique gives a good estimate of tumor hypoxia if the sampling is done in a uniform way with 5-6 tracks of 20-30 measurements each. Moreover, the analysis indicates that the accurate measurement of oxygen profile can be very useful in determining right radiation doses to the patients.

Resumo Limpo

tumor oxygen status consid one import prognost marker cancer sinc strong influenc respons cancer cell various treatment particular radiat therapi thus proper accur assess tumor oxygen distribut treatment may high affect outcom treatment heterogen natur tumor hypoxia main influenc complex tumor microenviron often make quantif difficult usual method use measur tumor hypoxia biomark polarograph needl electrod although techniqu may provid accept assess hypoxia invas may alway give spatial distribut hypoxia use treatment plan altern method quantifi tumor hypoxia use theoret simul knowledg tumor vasculatur purpos paper model tumor hypoxia use known spatial distribut tumor vasculatur obtain imag data analyz accuraci polarograph needl electrod measur quantifi hypoxia quantifi optimum number measur requir satisfactorili evalu tumor oxygen status studi effect hypoxia radiat respons result indic model success generat accur oxygen map tumor crosssect known vascular distribut method develop provid way estim tumor hypoxia provid guidanc plan accur effect therapeut strategi invas estim techniqu result agre previous find needl electrod techniqu give good estim tumor hypoxia sampl done uniform way track measur moreov analysi indic accur measur oxygen profil can use determin right radiat dose patient

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