Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

被引:38
作者
Kashkooli, Farshad Moradi [1 ]
Soltani, M. [1 ,2 ,3 ,4 ]
机构
[1] KN Toosi Univ Technol, Dept Mech Engn, Tehran, Iran
[2] Univ Waterloo, Dept Elect & Comp Engn, Waterloo, ON, Canada
[3] Univ Tehran Med Sci, Canc Biol Res Ctr, Canc Inst Iran, Tehran, Iran
[4] KN Toosi Univ Technol, Adv Bioengn Initiat Ctr, Computat Med Ctr, Tehran, Iran
关键词
METRONOMIC CHEMOTHERAPY; HETEROGENEOUS VASCULATURE; THEORETICAL-MODELS; DRUG-DELIVERY; PHASE-II; TRANSPORT; FLUID; MACROMOLECULES; PHARMACOKINETICS; SENSITIVITY;
D O I
10.1038/s41598-021-00989-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence. Three treatment approaches-maximum tolerated dose (MTD), metronomic chemotherapy (MC), and chemo-switching (CS)-as well as different chemotherapy schedules are investigated on a real tumor geometry extracted from image. Additionally, a sensitivity analysis of effective parameters of drug is carried out to evaluate the potential of using different other drugs in cancer treatment. The main findings are: (i) CS, MC, and MTD have the best performance in reducing tumor cells, respectively; (ii) multiple doses raise the efficacy of drugs that have slower clearance, higher diffusivity, and lower to medium binding affinities; (iii) the suggested approach to eradicating tumors is to reduce their cells to a predetermined rate through chemotherapy and then apply adjunct therapy.
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页数:15
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