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Quantitative Modeling On Tissue-Specific Stem Cell Amounts for Radiation Induced Normal Tissue Complications

K Wang*, M Huq, UPMC Hillman Cancer Center and University of Pittsburgh School of Medicine, Pittsburgh, PA

Presentations

PO-GePV-M-313 (Sunday, 7/10/2022)   [Eastern Time (GMT-4)]

ePoster Forums

Purpose: Normal tissue complications (NTCs) have been the major concern of radiotherapy for decades. In prevalent radiotherapy both IMRT and conventional fractionations (CF) are dedicated to reducing NTC probability. SBRT strategies could delivery higher fractional dose with acceptable toxicities due to more precise tissue sparing. In addition, the reasons for some mysterious NTC properties e.g., the 2-months late effect, remains unclear. We believe that NTC cannot be interpreted with classical radiobiology. However, by introducing tissue-specific stem cells (TSCs) and the related mechanism, we could establish a quantitative model to explore/explain NTCs which puzzled the field for decades.

Methods: Though the mechanism for radiation induced NTCs remained unclear, it would be fair to extrapolate that significant loss of local TSCs have caused self-reconstruction disability due to irradiations. The major difficulties to establish a theory on TSCs for NTCs include: TSC proliferation mechanism, the role of apoptosis in tissue reconstruction is still unclear, and the factor of radiation interferences. We first renovate several concepts which were assumed in classical radiobiology. In our renovated mitosis theory with TSCs, infinite proliferation is one of the key properties of TSCs rather than all normal cells. Based on this renovation we re-establish the theory of mitosis hierarchy, re-define the role of apoptosis and its limits.

Results: Our modeling is in the scope of a given organ/specific tissue, which NTC is typically considered. We first mathematically describe the general situation of zero radiation, and then revise our model by introduce the TSC loss caused by irradiations. The typical 2-month “late effect” for NTC occurrence is a nature predication of our model.

Conclusion: NTC could be predicted and modeled based on TSC amounts with radiation doses. For the first time, we provide a theoretical guidance for NTCs, and this could be a powerful tool for other physiological studies.

Keywords

NTCP, Radiation Effects, Radiobiology

Taxonomy

Not Applicable / None Entered.

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