Modeling the effect of intratumoral heterogeneity of radiosensitivity on tumor response over the course of fractionated radiation therapy
| العنوان: | Modeling the effect of intratumoral heterogeneity of radiosensitivity on tumor response over the course of fractionated radiation therapy |
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| المؤلفون: | Lawrence Berk, Juan Carlos López Alfonso |
| المساهمون: | BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany. |
| المصدر: | Radiation Oncology (London, England) Radiation oncology (London, England) Radiation Oncology, Vol 14, Iss 1, Pp 1-12 (2019) |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | lcsh:Medical physics. Medical radiology. Nuclear medicine, Radiobiology, Cell Survival, Radiation resistance, lcsh:R895-920, medicine.medical_treatment, Population, lcsh:RC254-282, Models, Biological, Radiation Tolerance, 03 medical and health sciences, 0302 clinical medicine, Radiation sensitivity, Cell Line, Tumor, Neoplasms, medicine, Humans, Linear-quadratic model, Distribution (pharmacology), Radiology, Nuclear Medicine and imaging, Radiosensitivity, education, education.field_of_study, Accelerated repopulation, business.industry, Research, Standard treatment, Dose-Response Relationship, Radiation, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Cancer research, Dose Fractionation, Radiation, Fractionated radiotherapy, Intratumoral radiosensitivity heterogeneity, business, Relative Biological Effectiveness |
| الوصف: | Background Standard radiobiology theory of radiation response assumes a uniform innate radiosensitivity of tumors. However, experimental data show that there is significant intratumoral heterogeneity of radiosensitivity. Therefore, a model with heterogeneity was developed and tested using existing experimental data to show the potential effects from the presence of an intratumoral distribution of radiosensitivity on radiation therapy response over a protracted radiation therapy treatment course. Methods The standard radiation response curve was modified to account for a distribution of radiosensitivity, and for variations in the repopulation rates of the tumor cell subpopulations. Experimental data from the literature were incorporated to determine the boundaries of the model. The proposed model was then used to show the changes in radiosensitivity of the tumor during treatment, and the effects of fraction size, α/β ratio and variation of the repopulation rates of tumor cells. Results In the presence of an intratumoral distribution of radiosensitivity, there is rapid selection of radiation-resistant cells over a course of fractionated radiation therapy. Standard treatment fractionation regimes result in the near-complete replacement of the initial population of sensitive cells with a population of more resistant cells. Further, as treatment progresses, the tumor becomes more resistant to further radiation treatment, making each fractional dose less efficacious. A wider initial distribution induces increased radiation resistance. Hypofractionation is more efficient in a heterogeneous tumor, with increased cell kill for biologically equivalent doses, while inducing less resistance. The model also shows that a higher growth rate in resistant cells can account for the accelerated repopulation that is seen during the clinical treatment of patients. Conclusions Modeling of tumor cell survival with radiosensitivity heterogeneity alters the predicted tumor response, and explains the induction of radiation resistance by radiation treatment, the development of accelerated repopulation, and the potential beneficial effects of hypofractionation. Tumor response to treatment may be better predicted by assaying for the distribution of radiosensitivity, or the extreme of the radiosensitivity, rather than measuring the initial, general radiation sensitivity of the untreated tumor. |
| تدمد: | 1748-717X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66072962a7c15a009991155baa6bc284 https://doi.org/10.1186/s13014-019-1288-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....66072962a7c15a009991155baa6bc284 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1748717X |
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