Application of organ tolerance dose-constraints in clinical studies in radiation oncology.

In modern radiation oncology, tolerance dose-constraints for organs at risk (OAR) must be considered for treatment planning, but particularly in order to design clinical studies. Tolerance dose tables, however, only address one aspect of the therapeutic ratio of any clinical study, i.e., the limitation of adverse events, but not the desired potential improvement in the tumor effect of a novel treatment strategy. A sensible application of "tolerance doses" in a clinical situation requires consideration of various critical aspects addressed here: definition of tolerance dose, specification of an endpoint/symptom, consideration of radiation quality and irradiation protocol, exposed volume and dose distribution, and patient-related factors of radiosensitivity. The currently most comprehensive estimates of OAR radiation tolerance are in the QUANTEC compilations (2010). However, these tolerance dose values must only be regarded as a rough orientation and cannot answer the relevant question for the patients, i.e., if the study can achieve a therapeutic advantage; this can obviously be answered only by the final scientific analysis of the study results. Despite all limitations, the design of clinical studies should currently refer to the QUANTEC values for appreciation of the risk of complications, if needed supplemented by one's own data or further information from the literature. The implementation of a consensus on the safety interests of the patients and on an application and approval process committed to progress in medicine, with transparent quality-assuring requirements with regard to the structural safeguarding of the study activities, plays a central role in clinical research in radiation oncology.