The HYP-RT Hypoxic Tumour Radiotherapy Algorithm and Accelerated Repopulation Dose per Fraction Study

Abstract

The HYP-RT model simulates hypoxic tumour growth for head and neck cancer as well as radiotherapy and the effects of accelerated repopulation and reoxygenation. This report outlines algorithm design, parameterisation and the impact of accelerated repopulation on the increase in dose/fraction needed to control the extra cell propagation during accelerated repopulation. Cell kill probabilities are based on Linear Quadratic theory, with oxygenation levels and proliferative capacity influencing cell death. Hypoxia is modelled through oxygen level allocation based on pO2 histograms. Accelerated repopulation is modelled by increasing the stem cell symmetrical division probability, while the process of reoxygenation utilises randomised pO2 increments to the cell population after each treatment fraction. Propagation of 108 tumour cells requires 5–30 minutes. Controlling the extra cell growth induced by accelerated repopulation requires a dose/fraction increase of 0.5–1.0 Gy, in agreement with published reports. The average reoxygenation pO2 increment of 3 mmHg per fraction results in full tumour reoxygenation after shrinkage to approximately 1 mm. HYP-RT is a computationally efficient model simulating tumour growth and radiotherapy, incorporating accelerated repopulation and reoxygenation. It may be used to explore cell kill outcomes during radiotherapy while varying key radiobiological and tumour specific parameters, such as the degree of hypoxia.

Altered fractionation outcomes for hypoxic head and neck cancer using theHYP-RTMonte Carlo model

“…The validity of the HYP-RT model compared with the standard LQ model (for oxic and hypoxic tumours) and the known limitations and assumptions of the cell growth and radiotherapy algorithms have been previously reported [3][4][5]. Statistical uncertainty in the model results arising from the use of different random number seeds continued to be in the range of 4-6 Gy in the current work [3].…”

“…The model incorporates a realistic epithelial cell hierarchy, tumour hypoxia and mimics the effects of AR and ROx during radiotherapy-induced tumour shrinkage [3][4][5].…”

“…The HYP-RT temporal tumour growth algorithm has been reported and justified in detail [4,5], and therefore the description of the modelling methods in the current report is brief. This has previously included explanations about the values and ranges of cell and environmentbased default model parameters and how these are allocated using random number generation and stored for each cell.…”

“…The OER factor is applied in terms of a "reduction in death probability" factor based on the cell's pO 2 level and use of normalised OER curves. The three different OER curves shown in Figure 2 were normalised by scaling them to have maximal values of 1.0 at 60 mmHg [4]. The final death probability of a cell could then be calculated as (12SFd) multiplied by the OER factor.…”

“…Model outcomes that compare the doses required for 100% tumour control (for "moderately hypoxic" tumours [3,4]) are presented in Figure 3a,b for seven AR and ROx onset time combinations, illustrating the full range of dose outcomes arising owing to the onset time variations, for each of the 11 schedules. Figure 3a shows that the ranges in results caused by altering AR Figure 3.…”