Methods in the HYP-RT MC Code
Starting from 1 clonogenic tumour cell,
108 cell tumours were generated.
Tumours were based on HNSCC cell proliferative hierarchy,
cell kinetic and radiation response parameters (α=0.3 Gy-1,β=0.03 Gy-2)2,4-5 [FIGURE 1].
To simulate radiative cell death,
the code analysed each tumour cell individually for each dose fraction and calculated a probability of death based on the LQ (or LQC equation),
the oxygen enhancement ratio (OER) of the cell (dependent on pO2) and a cell phase factor or quiescence factor (quiescent due to differentiation status or severe hypoxia,
i.e.
pO2 ≤2 mm Hg).
Cell death was carried out if a random number was generated in the correct range (less than the probability of death described above) or else the cell was left to proliferate.
Severely hypoxic cells could also die if not reoxygenated with 4 days.
Differentiated cells died from natural cell death after 7 days.
Oxygen enhancement ratios (OER) of 1-3 were applied6 based on the simulated pO2 histograms shown in FIGURE 2,
which were based on cell population numbers,
to represent gradual oxygen deprivation during growth as well as gradual reoxygenation during treatment.
In HYP-RT,
LQ equations were modified to LQC equations through the use of a “γ” term,
where γ =β /3DL and basic cell survival,
S,
(before phase and oxygenation modification) became: ln(S) = αd+βd2-γd3 3.
Five schedules were simulated [TABLE 1],
as were three choices of DL: 10,
18 and infinite i.e.
γ=0.
FIGURE 3 displays the three cell survival functions applied. No cell repair was modelled,
however continual proliferation was considered,
neglecting accelerated repopulation in this study due to the short fractionation schedules being analysed.
Simulations were repeated at least 9 times for each parameter set (3 random growth seeds and 3 random treatment seeds).
All result data is displayed with errors in terms of 1 SD.
Schedule (Gy/#)
|
Days/week
|
2
|
5 (mon to fri)
|
6
|
3 (mon,
wed,
fri)
|
9
|
3 (mon,
wed,
fri)
|
12
|
2 (mon,
thurs)
|
15
|
2 (mon,
thurs)
|
TABLE 1: SBRT and conventional schedules simulated.