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.

Suppression of amygdala kindling with short interstimulus intervals: effect of norepinephrine depletion.

The rate of development of generalized kindled convulsions was profoundly influenced by the interval between amygdala stimulations. With stimulation every 10 min, nearly complete interference with the progression of kindling was observed in most rats, and hourly stimulation precipitated kindling rates three times longer than did once per day. Depletion of norepinephrine (NE), as a result of intracerebroventricular pretreatment with 6-hydroxydopamine, virtually eliminated the interference with kindling development seen in the vehicle control rats. Such depletion of NE, however, had little influence on the generalized responses once developed. At this stage, interference with seizure provocation was observed as truncated electroencephalographic seizures which were usually devoid of motor correlates. This interference was more profound in the shorter interstimulus intervals and was independent of NE depletion. Finally, when changing from the short kindling intervals of 10 min and 1 h to the longer interval of 24 h, an unexpected interference with seizure provocation was observed. The implication of these results for the biochemical basis of kindling and kindling as a model of learning are discussed.