Uncertainties in physical and biological targeting with radiation therapy.

Advances in radiation therapy over the past decade have resulted from increased accuracy of imaging and highly conformal three dimensional treatment planning and delivery of radiation therapy. Three-dimensional conformal radiation therapy (3D CRT) with higher doses than previously considered tolerable is now standard for many types of cancer. Intensity modulated radiation therapy (IMRT) with x-rays, proton beam treatments and intensity modulated proton therapy (IMPT) are major areas of research. Tumor motion between and even during radiation treatments represents a major uncertainty. Tumor heterogeneity results in additional uncertainties affecting tumor control with radiation therapy. Imaging the heterogeneous targets within tumors offers new opportunities for tumor delineation. Molecular therapeutic agents enhance the effects of ionizing radiations in murine systems. Clinical trials combining molecular targeting agents with conformal radiation therapy are being initiated.