Radiobiological modeling and clinical trials.
OBJECTIVE
Standard clinical trial designs can lead to restrictive conclusions: the "best recommended treatments" based on trial results, although generally applicable to patient populations, do not necessarily apply to individual patients. In theory, radiobiological modeling, coupled with reliable predictive assays, can be used to rationalize the selection of patients for particular schedules in trials.


METHODS
Linear-quadratic modeling of radiotherapy can be used to simulate a clinical trial. This is achieved by random sampling techniques where the key radiobiological parameters (alpha, beta, T(pot) and clonogen number) are selected from known or expected ranges. Clinical trial design in radiotherapy may be improved by formal radiobiological assessment designed to estimate the likely changes in tumor cure probability (TCP) and the likely normal tissue biologically effective dose (BED). Modeling may also be used to rationalize the allocation of patients to a test or standard schedule or for individual optimization of a treatment schedule. Such approaches depend on there being reliable predictive assays of the radiobiological parameters in individual patients. The influence of variations in predictive assay accuracy on the improved outcomes are assessed.


RESULTS
Clinical trials, which have been preceded by modeling simulation, offer potentially substantial improvements in the results of cancer treatment by radiotherapy. These exceed the usual gains found in standard clinical trials.


CONCLUSIONS
Future preclinical trial design should include modeling assessments that indicate how best to structure the trial.
Clinical Oncology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
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Jones
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Dale
D002455:Cell Division; D003198:Computer Simulation; D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D009369:Neoplasms / Q000532:radiotherapy*; D018579:Patient Selection; D011379:Prognosis; D011836:Radiation Tolerance; D011853:Radiobiology; D016032:Randomized Controlled Trials as Topic; D012062:Relative Biological Effectiveness; D012107:Research Design; D013997:Time Factors