Clinical validation of the LKB model and parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy.

The choice of the appropriate model and parameter set in determining the relation between the incidence of radiation pneumonitis and dose distribution in the lung is of great importance, especially in the case of breast radiotherapy where the observed incidence is fairly low. From our previous study based on 150 breast cancer patients, where the fits of dose-volume models to clinical data were estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the relative seriality is significantly better than the LKB NTCP model. However, the estimation of the different NTCP models was based on their goodness-of-fit on clinical data, using various sets of published parameters from other groups, and this fact may provisionally justify the results. Hence, we sought to investigate further the LKB model, by applying different published parameter sets for the very same group of patients, in order to be able to compare the results. It was shown that, depending on the parameter set applied, the LKB model is able to predict the incidence of radiation pneumonitis with acceptable accuracy, especially when implemented on a sub-group of patients (120) receiving [see text]|EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain radiobiological model on a given clinical case is closely related to the selection of the proper scoring criteria and parameter set as well as to the compatibility of the clinical case from which the data were derived.

Quality assurance in radiotherapy of breast cancer--variability in planning target volume delineation.

The inter-physician and inter-patient variability in planning target volume delineation for the radiotherapy of breast cancer after conservative surgery is presented. Eleven experienced radiation oncologists determined the planning target volume (PTV) for four breast cancer patients. Delineation was based on CT slices taken at intervals of 15 mm. The variability in target volume delineation was determined by measuring the volumes in units of cc and the position of the drawn PTVs. Statistical analysis was based on X/R-charts and on Pareto chart and analysis. The maximum range in PTV for one patient was from 670 to 1,200 cc. The observations of three physicians were in excess of the warning limit altogether 18 times. The methods used in this study clearly reveal inter-physician variability in PTV delineation and widest variations found are not acceptable. Training targeted to some physicians and more detailed and unambiguous protocols for PTV delineation are needed.

The influence of electromagnetic interference and ionizing radiation on cardiac pacemakers.

Adverse effects of the ionizing and non-ionizing electromagnetic fields on five pacemaker models have been tested. The study consisted of three parts: 1. measurement of magnetic fields in a radiotherapy room (microtron MM14), 2. the application of non-ionizing electromagnetic fields on pacemakers in a test laboratory (1...1000 microT, 10...10000 Hz), and 3. the application of ionizing radiation of different types of radiotherapy devices on the pacemakers. The magnetic field strength in the microtron treatment room was found to be under 7.5 microT, which is one order of magnitude lower than the tolerance level obtained for the pacemakers in the test laboratory. All the tested pacemakers tolerated the ionizing radiation dose levels (less than 60 Gy) which are used in the radiotherapy.

Effects of fractionated radiotherapy on bone blood flow in man.

Effects of fractionated irradiation on bone blood flow during and some months after the radiotherapy were measured with a 133Xe washout method from the greater trochanteric regions of human femurs. The results suggest that at low dose levels (CRE from 250 to 1050 reu) the decrease in bone blood flow is small. However, there seems to be a significant decrease in blood flow (about 50%) several months after the irradiation.

Effects of local single and fractionated X-ray doses on rat bone marrow blood flow and red blood cell volume.

Time and dose dependent changes in blood flow and red blood cell volume were studied in the locally irradiated bone marrow of the rat femur after single and fractionated doses of X-rays. With the single dose of 10 Gy the bone marrow blood flow although initially reduced returned to the control levels by seven months after irradiation. With doses greater than or equal to 15 Gy the blood flow was still significantly reduced at seven months. The total dose levels predicted by the nominal standard dose equation for treatments in three, six or nine fractions produced approximately the same degree of reduction in the bone marrow blood flow seven months after the irradiation. However, the fall in the red blood cell volume was from 23 to 37% greater in the three fractions groups compared with that in the nine fractions groups. Using the red blood cell volume as a parameter the nominal standard dose formula underestimated the severity of radiation damage in rat bone marrow at seven months for irradiation with small numbers of large dose fractions.

Response of rat brain tissue for the extraction of 125I antipyrine after single and fractionated roentgen ray doses. A comparison of fractionation models applied to the central nervous system.

Changes in the cerebral blood flow in rats were studied 9 months after irradiation with single and fractionated doses of 250 kV roentgen rays. The single doses used were 11.9, 14.5, 17.0, 19.6 and 22.1 Gy. Corresponding fractionated doses (FD) were calculated by the formula: FD = single dose X N0.42, where N is the number of fractions. The fractionated doses were given as 4, 7 and 10 dose fractions in the same overall treatment time of 3 weeks. The blood flow changes were estimated by the 125I antipyrine extraction technique. In the non-irradiated control group the extraction in the brain was 0.93 per cent of the injected dose of 125I antipyrine per g of tissue. In the irradiated rats the corresponding extraction was on average 20.4 per cent higher than that in the control group. The extraction was significantly increased in 7 of the 20 irradiated groups of animals. The fractionation model used in these experimental studies is compared with other published fractionation models for radiation tolerance of the rat and human brain and spinal cord.

Late radiation damage to the rat femur and the NSD formula.

The extraction of 86Rb chloride, the red blood cell volume and the mineral content in the rat femur have been studied 7 months after local X-irradiation. Doses were given as 3, 6 and 9 fractions over three weeks. The total doses used were based on NSD value of 1450 and 1900 on the basis of the results from our previous single dose irradiation studies. The reduction in the extraction of 86Rb chloride was statistically significant for all fractionation schemes and at both NSD levels. In the whole femur, with bone marrow, the extraction was reduced by 33% to 46%. In the hard bone the reduction was less only 18% to 38%. There was no significant difference between the fractionation schemes used at each NSD level. The red blood cell volume was significantly reduced in the whole femur, with bone marrow, with no difference between the fractionation schemes. However, there was no change in the hard bone. The dry bone weight was reduced by 3 to 6% with no significant difference between the different fractionation schemes. The dose levels predicted by the NSD formula produced approximately the same damage to the rat femur 7 months after the irradiation when the dry weight and the extraction of 86Rb chloride were used as end points for the evaluation of the severity of late radiation damage.

Functional changes in the vascularity of the irradiated rat femur. Implications for late effects.

Early and late changes in the extraction of 125I antipyrine was investigated in the rat femur after local irradiation with single doses of 5 to 25 Gy. The extraction of antipyrine by bone was generally reduced after irradiation, with the greatest effect being found 3 months after treatment. However, the effect was transient and by 7 months after less than or equal to 20 Gy, antipyrine extraction was similar to that in the normal femur. Extraction was still reduced after 25 Gy. The first significant reduction in dry bone weight occurred 7 months after 15, 20 and 25 Gy. The fall in the calcium and phosphorus content of bone was similar to that of the dry bone weight. Calcium/phosphorus ratio was not modified in irradiated bone. The likely role of the vascular changes in the subsequent development of bone atrophy is discussed.

Radiation-induced changes in regional blood flow in human tumors.

In 43 patients the blood flow in 48 superficial metastatic tumors was measured with the 133xenon wash-out method. In all cases the blood flow was measured before the start of radiotherapy and then one week later during radiotherapy. In 36 cases the blood flow was measured after 2 weeks during radiotherapy, and in six patients the follow-up lasted 5-6 weeks. The blood flow increased during the first week of radiotherapy in the whole series from 20.1 +/- 18.0 ml/min/100g to 31.3 +/- 24.9 ml/min/100g. The increase during the first week was significant (p less than 0.001). During the second week of radiotherapy the blood flow decreased to 27.0 +/- 19.3 ml/min/100g; the decrease was also significant (p less than 0.05). The changes in the different tumor groups during radiotherapy seemed to be in the same direction. In a longer follow-up the gradual decrease in the blood flow seemed to continue.