Individualizing cancer treatment: Biological optimization models in treatment planning and delivery

Purpose: During the last 30 years radiation therapy has developed from classical rectangular beams via conformation therapy with largely uniform dose delivery, but irregular field shapes, to fully intensity modulated dose delivery where the total dose distribution in the tumor can be fully controlled in three dimensions. This last step has been developed during the last 15-20 years and has opened up the possibilities for truly optimized radiation therapy. Methods and Materials: Today it is not only possible to produce almost any desired dose distribution in the tumor volume. It is also possible to deliver the dose distribution, which has the highest probability to cure the patient without inducing severe complications in normal tissues. To fully exploit the advantages of intensity-modulated radiation therapy, quality of life or radiobiologic objectives have to be used, preferably combined with predictive assay of radiation sensitivity. Results: This article will briefly discuss the biologic objective functions and the associated advantages in the treatment outcome using new approaches such as consideration of stochastic variations in sensitivity and optimization of the angle of incidence and fractionation schedule with intensity-modulated beams. Finally, different possibilities for realizing general three-dimensional intensity-modulated dose delivery will be discussed. Conclusions: Once accurate genetically and/or cell survival based predictive assays become available, radiation therapy will become an exact science allowing truly individual optimization considering also the panorama of side-effects that the patient is willing to accept. (C) 2001 Elsevier Science Inc.