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In the lifetime prediction and extension of a nuclear power plant, a reactor pressure vessel (RPV) has to demonstrate the exclusion of brittle fracture. This paper aims to apply fracture mechanics to analyse the non-uniform cooling effect in case of a loss-of-coolant accident on the RPV integrity. A comprehensive framework coupling reactor system, fluid dynamics, fracture mechanics, and probabilistic analyses for the RPVs integrity analysis is proposed. The safety margin of the allowed RTNDT is increased by more than 16°C if a probabilistic method is applied. Considering the non-uniform plume cooling effect increases KI more than 30%, increases the failure frequency by more than 1 order of magnitude, and increases the crack tip constraint due to the resulting higher stress. Thus, in order to be more realistic and not to be nonconservative, 3D computational fluid dynamics may be required to provide input for the fracture mechanics analysis of the RPV. [ABSTRACT FROM AUTHOR]