A method of calibrating a resistance region focused, RRF, dose in a radiotherapy treatment plan for a tumor using a phantom model, the method comprising: a. obtaining a three-dimensional image of a tumor in a patient; b. identifying a peripheral boundary of the tumor using the three-dimensional image; c. identifying a hypoxic region within the tumor using the three-dimensional image; d. designating a region immediately inside the peripheral boundary as a sensitive region, the sensitive region having an average width W; e. designating a region between the hypoxic region and the sensitive region as a resistance region; the method being characterised by the following steps: f. generating a radiation treatment plan, the treatment plan comprising: i. a hypoxic region focused, HRF, dose, the HRF dose directed to the hypoxic region; ii. a resistance region focused, RRF, dose, lower than the HRF dose but boosted above a spillover dose from the HRF dose, the RRF dose directed to the resistance region; and iii. a sensitive region focused, SRF, dose, lower than the RRF dose, the SRF dose directed to the sensitive region; g. irradiating a phantom following the treatment plan; h. measuring the irradiation in said phantom; i. testing the measured irradiation to the phantom region corresponding to the peripheral boundary to determine if the boosted RRF dose had increased irradiation at the peripheral boundary above a threshold value; and j. calibrating the RRF dose based on the determination of the irradiation to the phantom region corresponding to the peripheral boundary. a. obtaining a three-dimensional image of a tumor in a patient; b. identifying a peripheral boundary of the tumor using the three-dimensional image; c. identifying a hypoxic region within the tumor using the three-dimensional image; d. designating a region immediately inside the peripheral boundary as a sensitive region, the sensitive region having an average width W; e. designating a region between the hypoxic region and the sensitive region as a resistance region; the method being characterised by the following steps: as a resistance region; the method being characterised by the following steps: f. generating a radiation treatment plan, the treatment plan comprising: i. a hypoxic region focused, HRF, dose, the HRF dose directed to the hypoxic region; ii. a resistance region focused, RRF, dose, lower than the HRF dose but boosted above a spillover dose from the HRF dose, the RRF dose directed to the resistance region; and iii. a sensitive region focused, SRF, dose, lower than the RRF dose, the SRF dose directed to the sensitive region; i. a hypoxic region focused, HRF, dose, the HRF dose directed to the hypoxic region; ii. a resistance region focused, RRF, dose, lower than the HRF dose but boosted above a spillover dose from the HRF dose, the RRF dose directed to the resistance region; and iii. a sensitive region focused, SRF, dose, lower than the RRF dose, the SRF dose directed to the sensitive region; g. irradiating a phantom following the treatment plan; h. measuring the irradiation in said phantom; i. testing the measured irradiation to the phantom region corresponding to the peripheral boundary to determine if the boosted RRF dose had increased irradiation at the peripheral boundary above a threshold value; and j. calibrating the RRF dose based on the determination of the irradiation to the phantom region corresponding to the peripheral boundary. <EOS>