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The research logic of radiation oncology in combined modality therapy.

The integration of radiation, chemotherapy, and surgery depends on the delineation of failure patterns for each specific cancer. By identifying the failure pathways it is possible to design therapeutic strategies for each pattern. The main issues focus upon selecting the best therapeutic sequence and combination that can be employed first to reduce the tumor to subclinical stages, but ultimately to achieve a total cure. Although radiation therapy and chemotherapy can be given simultaneously or sequentially the variety of drugs now available and the many dose schedules for radiation therapy and chemotherapy make the possible permutations almost infinite. It is for this reason that the drug-radiation therapy interactions should be better understood, and that is why new terminology is being developed to describe the different types of interactions that may occur. With the innovations in radiation therapy (systemic half-body irradiation, radiosensitizers, and hyperthermia), there are now more potential combinations of standard modalities and new investigative techniques than can be explored clinically. For this reason, experimental models may be able to offer a better scientific basis for combining modes, but even in the laboratory too many probabilities exist. The need for a cooperative effort (both in laboratory and clinical investigations) for combined modality treatment approaches to cancer has become a mandate for oncology protocol design in this multimodal era.