A computer implemented method for interactively manipulating dose distribution of a radiation treatment plan configured to be used by an external-beam radiation treatment system, the method comprising: Obtaining, by a computer system, an initial radiation treatment plan, the initial radiation treatment plan producing an initial dose distribution that satisfies a plurality of clinical goals, wherein the plurality of clinical goals are expressed in terms of a plurality of initial threshold values for a plurality of quality indexes, each quality index relating to a respective statistical quantity of the initial dose distribution; the method further comprising: converting, by the computer system, the plurality of clinical goals into a plurality of constraints relating to the plurality of quality indexes, each constraint having a respective initial reference value corresponding to the initial threshold value of the respective quality index, each respective constraint having a corresponding priority indicating relative importance of the respective constraint among the plurality of constraints; providing a user interface to a user, the user interface allowing the user to change an initial reference value to a new reference value for one of the plurality of constraints; and performing, by the computer system, re-optimization of the initial radiation treatment plan to obtain an updated radiation treatment plan using the new reference value for the one of the plurality of constraints, the updated radiation treatment plan producing an updated dose distribution, wherein the re-optimization enforces the updated dose distribution to satisfy any constraint that has a priority higher than a priority of the one of the plurality of constraints while allowing any constraint that has a priority lower than the priority of the one of the plurality of constraints to be violated. Obtaining, by a computer system, an initial radiation treatment plan, the initial radiation treatment plan producing an initial dose distribution that satisfies a plurality of clinical goals, wherein the plurality of clinical goals are expressed in terms of a plurality of initial threshold values for a plurality of quality indexes, each quality index relating to a respective statistical quantity of the initial dose distribution; the method further comprising: converting, by the computer system, the plurality of clinical goals into a plurality of constraints relating to the plurality of quality indexes, each constraint having a respective initial reference value corresponding to the initial threshold value of the respective quality index, each respective constraint having a corresponding priority indicating relative importance of the respective constraint among the plurality of constraints; providing a user interface to a user, the user interface allowing the user to change an initial reference value to a new reference value for one of the plurality of constraints; and performing, by the computer system, re-optimization of the initial radiation treatment plan to obtain an updated radiation treatment plan using the new reference value for the one of the plurality of constraints, the updated radiation treatment plan producing an updated dose distribution, wherein the re-optimization enforces the updated dose distribution to satisfy any constraint that has a priority higher than a priority of the one of the plurality of constraints while allowing any constraint that has a priority lower than the priority of the one of the plurality of constraints to be violated. converting, by the computer system, the plurality of clinical goals into a plurality of constraints relating to the plurality of quality indexes, each constraint having a respective initial reference value corresponding to the initial threshold value of the respective quality index, each respective constraint having a corresponding priority indicating relative importance of the respective constraint among the plurality of constraints; providing a user interface to a user, the user interface allowing the user to change an initial reference value to a new reference value for one of the plurality of constraints; and performing, by the computer system, re-optimization of the initial radiation treatment plan to obtain an updated radiation treatment plan using the new reference value for the one of the plurality of constraints, the updated radiation treatment plan producing an updated dose distribution, wherein the re-optimization enforces the updated dose distribution to satisfy any constraint that has a priority higher than a priority of the one of the plurality of constraints while allowing any constraint that has a priority lower than the priority of the one of the plurality of constraints to be violated.