Predicting Normal Tissue Complications In Radiotherapy

.> Introduction Patient-to-patient variations in the radiosensitivity of normal and neoplastic tissues are well known and recognized both in vivo(1.2) and in vitro studies. (3.6) The typical example is the autosomal recessive disease ataxia-telangiectasia (AT). ATM patients are extremely sensitive to ionizing radiation. The patients develop severe to fatal radiation reactions when treated by standard radiotherapy regimens. Between those and normally sensitive patients, there is a wide range of radiosensitivity. These differences in the response to treatment raised the possibility of individualizing the dose prescription. Therefore, considerable interest in the development of predictive assays have emerged. The predictive test should have acceptable accuracy to enable screening between patients on the basis of their radiosensitivity in order to tailor the radiotherapy treatment to their expected clinical response. Even though predicting the tumor response to radiotherapy has been attempted by many studies, (7.8) this review will be limited to studies that are concerned with predicting the radiation effects on normal tissues. The tolerance of normal tissues is what actually constitutes the limiting factor for dose escalation in radiotherapy. Also, the concept of tumor resistance is relative since the tolerance of normal tissues prevents increasing the radiation dose to control the tumor. (9) Therefore, a better knowledge of normal tissue tolerance would appear critical in the search for improving the efficacy of radiotherapy and to increase the therapeutic ratio. The objective is to tailor radiotherapy treatment to each individual patient's radiosensitivity. Radiation doses could be reduced for the small radiosensitive subset of patients (about 5%) (10) and increased for the more resistant once. This dose modulation is expected to increase local control while reducing radio toxicity or at least keeping it to an acceptable