On the other hand, the doses to lens to cause cataract might not be a good indicator to compare the two optimization methods as cataract could be corrected by surgery and it was sometimes debatable to consider it as BU 4061T clinically relevant toxicity. It has been reported that by solely using TCP/EUD as the objective function would result in highly inhomogeneous target doses. TCP/EUD is less sensitive to hot spots as they help maximize target-cell kill. It is believed that adding some physical dose cost functions during the optimization process might help to improve the target dose homogeneity. In this study, two additional physical constraints were used, namely, the Uniformity constraint and the Max Dose constraint. The Uniformity constraint was set to 1% and the Max Dose was set to 72 Gy or lower for PTV70. Although the amount of hot spots and the maximum doses within targets were substantially reduced by adding these physical constraints, the HI, V110% and V107% values still reflected that BBTP plans produced inferior target dose homogeneity with more hot spots when compared to the DVTP plans. During the dose volume based optimization, hot spots found within the target volumes could be contoured as virtual organs. They could then be effectively removed by setting upper dose limits with desired priority after several repeated optimization cycles. The authors had attempted similar strategy for biological optimization but it was not effective. This might be due to the fact that achieving the desired TCP and Target EUD were inherently given higher priorities compared to the physical dose constraints during optimization. The current BBTP approach does not allow the users to specify the priority of physical constraints like Max Dose and Uniformity. It is highly desirable if priority could be given to these constraints so that the users could have a better control of the target dose homogeneity. The advantage of providing better sparing of parotid glands was counter-balanced by producing more hot spots within the targets. However, whether the appearance of hot spots within the target volumes is clinically undesirable or not is debatable. Hot areas within the tumor bed were commonly found when using stereotactic radiotherapy and brachytherapy. Hot areas and higher maximum doses could be beneficial to advanced stage diseases if they were located within the gross tumor volume, as reflected from the higher TCP values for the BBTP plans observed in the advanced NPC cases in the current study. Unfortunately, some hot spots might be found at undesirable locations close to or in the skull base. According to our clinical practice, not all vessels and nerves close to or in the skull base are contoured as OARs. It is therefore easy to miss them during plan evaluation. Hot spots in the skull base can inadvertently cause radiation damage to structures like carotid artery pseudoaneurysm and hypoglossal nerves palsies. .