Linear quadratic modeling of increased late normal-tissue effects in special clinical situations

Purpose: To extend linear quadratic theory to allow changes in normal-tissue radiation tolerance after exposure to cytotoxic chemotherapy, after surgery, and in elderly patients. Methods: Examples of these situations are analyzed by use of the biologic effective dose (BED) concept. Changes in tolerance can be allowed for by: estimation of either the contribution of the additional factor as an equivalent BED or the equivalent dose in 2-Gy fractions or by the degree of radiosensitization by a mean dose-modifying factor (x). Results: The estimated x value is 1.063 (95% confidence limits for the mean, 1.056 to 1.070) for subcutaneous fibrosis after cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and radiotherapy in breast cancer. The point estimate of x is 1.18 for the additional risk of gastrointestinal late-radiation effects after abdominal surgery in lymphoma patients (or 10.62 Gy at 2 Gy per fraction). For shoulder fibrosis in patients older than 60 years after breast and nodal irradiation, x is estimated to be 1.033 (95% confidence limits for the mean, 1.028 to 1.0385). The equivalent BED values were CMF chemotherapy (6.48 Gy(3)), surgery (17.73 Gy(3)), and age (3.61 Gy(3)). Conclusions: The LQ model can, in principle,, be extended to quantify reduced normal-tissue tolerance in special clinical situations. (C) 2006 Elsevier Inc.