The optimization dose priorities were consistent for all cases. Giving enough dose coverage to PTVs and limiting the maximum doses to brain stem, spinal cord and optic nerves were given the highest priority, followed by reducing the dose to parotid glands. Lower priorities were given to the other critical organs. To improve the target conformity, an optimization criterion was also assigned to an organ representing normal tissues, which was defined as the body volume in the CT data set minus the PTV leaving a 3 mm gap. For early stage cases, the prescription doses to targets were given in 35 daily fractions. For the advanced cases, the prescription doses were given in 33 daily fractions. The constraints listed in table 1 were also used as the plan acceptability criteria when performing the BBTP. Biological optimization in the Eclipse system is not a built-in option, but is an add-on software component developed by RaySearch Laboratories. It can produce an ideal set of fluence maps for the IMRT treatment plan based on LEE011 radiobiological models using a combination of biological and physical criteria. The plans created by biological optimization can be evaluated using the build-in dose volume analysis tool and/or the add-on biological evaluation tool. The objective functions which are to be maximized or minimized during the optimization include the TCP Poisson-LQ and the NTCP Poisson-LQ. The TCP and NTCP Poisson-LQ could be obtained either based on the Linear Quadratic cell survival model or equivalently the Linear dose-response model with the Equivalent dose in 2-Gy fractions. The relative seriality model proposed. was used for NTCP Poisson-LQ. A high value of seriality would be used for serial organs that were sensitive to high local doses even though the mean doses were low, while a lower value of seriality would be used for parallel organs that were less sensitive to local high doses, but still affected by high and low doses. When both TCP functions for targets and NTCP functions for OARs are defined for a task, the probability for complication free tumor control would become the objective function. This was an attempt to combine the individual TCPs and NTCPs into a single measure of the plan quality. Prior to the biological optimization, at least one TCP has to be defined for the target structure. In addition to the objective functions, a number of optional constraints could be defined by the users and were listed in table 2. The goal of optimization was to produce the best value of the objective function without violating any of the constraints. The biological functions and additional constraints that were used for the biological optimization of the NPC cases were listed in table 3. The Poisson TCP was only applied to PTV70 that included the tumor bed. The target EUD was used for each individual target to achieve multiple dose levels.