Linear quadratic modeling of increased late normal-tissue effects in special clinical situations.
OBJECTIVE
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 Gy3), surgery (17.73 Gy3), and age (3.61 Gy3).


CONCLUSIONS
The LQ model can, in principle, be extended to quantify reduced normal-tissue tolerance in special clinical situations.
Jones
Bleddyn
B
Birmingham Cancer Centre, Queen Elizabeth University Hospital, Birmingham, UK. b.jones.1@bham.ac.uk
Dale
Roger G
RG
Gaya
Andrew M
AM
D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D016014:Linear Models; D008223:Lymphoma / Q000532:radiotherapy; D008727:Methotrexate / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology*; D012062:Relative Biological Effectiveness; D013514:Surgical Procedures, Operative
D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate