دورية أكاديمية
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: | J. C. L. Alfonso, L. Berk |
المصدر: | Radiation Oncology, Vol 14, Iss 1, Pp 1-12 (2019) |
بيانات النشر: | BMC, 2019. |
سنة النشر: | 2019 |
المجموعة: | LCC:Medical physics. Medical radiology. Nuclear medicine LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
مصطلحات موضوعية: | Intratumoral radiosensitivity heterogeneity, Radiation resistance, Linear-quadratic model, Fractionated radiotherapy, Accelerated repopulation, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | Abstract 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1748-717X |
Relation: | http://link.springer.com/article/10.1186/s13014-019-1288-y; https://doaj.org/toc/1748-717X |
DOI: | 10.1186/s13014-019-1288-y |
URL الوصول: | https://doaj.org/article/a59837aa269041ddb5f439e7e5e72e5e |
رقم الأكسشن: | edsdoj.59837aa269041ddb5f439e7e5e72e5e |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 1748717X |
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DOI: | 10.1186/s13014-019-1288-y |