Table 1. Cellular and algorithm design-based parameters in the HYP-RT model used to simulate tumour growth and fractionated radiotherapy.
Parameter | Default | User input | Range | References | Comments |
Cell total | 108 | Yes | Up to 108 | N/A | Tumour cell limit in the growth algorithm. |
Cell cycle time (stem cell) | 27 h | No | Gaussian, sigma = 3 h | Indirect: Begg et al [43], Mantel et al [44], Steel [45], Wilson et al [46] | The G0 phase adds to the length to the stem cell cycle time. Infinite division capability of these cells. |
Cell cycle time (transit cell) | 33 h | No | Gaussian, sigma = 3 h | Gaussian, sigma = 6 h | Limited to 2–4 generations of division. |
Differentiating time: D1 and D2 cells | D1: 36 hD2: 36 h | No | Uniform: range of 24–48 h | Indirect: Wilson et al [46], Potten et al [47] | Estimated based on 1–2 week cell turnover in epithelial tissue. |
Fully differentiated D3 cell natural death rate | D3: 80% | No | Constant | Indirect: Steel [45] (approximately 85% cell loss factor) | This cell loss rate for the fully differentiated cells means that the total average cell loss is approximately 85% for the whole population where TD is approximately 40–45 days. |
Stem cell division products i.e. the S:T:D1 ratio | S = 3% T = 87% D1 = 10% | Yes | Constant | Steel [45] | This ratio produces an approximate 1% stem cell population in the tumour |
Low oxygen limit for cell cycle arrest | 1 mmHg | Yes | Constant | Indirect: Alarcon [34], Ljungkvist et al [48] | Hypoxia induced quiescence is initiated at this pO2. |
Percentage of cells exiting the cell cycle (with pO2 <1 mmHg) | 50% | Yes | 1–100% | N/A | Set so that the total number of hypoxia induced quiescent cells (<1 mmHg) = 3%, in line with the pO2 specific histogram used. |
Hypoxic cell half-life (due to necrosis: pO2 <1 to 2 mmHg) | 4 days | Yes | Constant | Durand and Sham [35], Ljungkvist [48] | 4–10 day hypoxic cell lifetime in human colon carcinoma spheroids, 2 days in HNSCC xenografts. |
AR onset time after RT initialisation (weeks) | No AR | Yes | 0, 1, 2, 3 | Withers et al [10], Marcu et al [12], Maciejewski et al [40], Peters and Withers [49], Terhaard et al [50], Trott [51], Trott and Kummermehr [52] | The number weeks into RT that AR is initiated, 2–4 weeks observed in references, however in this small tumour system. “0” weeks is used by default to initiate the microscopic response. |
ROx onset time after RT initialisation (weeks) | No ROx | Yes | 0, 1, 2, 3 | N/A | The number of weeks into RT that ROx is initiated. This is an extremely variable parameter and open to user input. |
Time of ROx after a particular RT fraction | 4 h | Yes | 1 to 23 | Ljungkvist et al [38] | Factor increase in stem cell symmetrical division due to AR. |
AR Spercent, factor increase in the symmetrical stem cell division probability | 10 | Yes | 1.1 to 30.0 | Marcu et al [12], Steel [45], Marcu et al [53] | |
ROx induced incremental increases in pO2 | 3 mmHg | Yes | 1 to 5 | N/A | pO2 increment size during randomised ROx after a RT fraction (linearly SF dependent), set to obtain full oxygenation by approximately 1 to 2 mm tumour diameter. |
Alpha (LQ model) | 0.3 | Yes | 0.1 to 1.0 | Horiot et al [54], Stuschke and Thames [55] | Used in SF calculations (LQ equation). |
Beta (LQ model) | 0.03 | Yes | 0.01 to 0.1 | Horiot et al [54], Stuschke and Thames [55] | Used in SF calculations (LQ equation). |
RT, radiotherapy; ROx, reoxygenation; SF, surviving fraction; AR, accelerated repopulation; LQ, linear quadratic; HNSCC, head and neck small cell carcinoma.