Sensitivity analysis of parameters in linear-quadratic radiobiologic modeling.
OBJECTIVE
Radiobiologic modeling is increasingly used to estimate the effects of altered treatment plans, especially for dose escalation. The present article shows how much the linear-quadratic (LQ) (calculated biologically equivalent dose [BED] varies when individual parameters of the LQ formula are varied by +/-20% and by 1%.


METHODS
Equivalent total doses (EQD2 = normalized total doses (NTD) in 2-Gy fractions for tumor control, acute mucosal reactions, and late complications were calculated using the linear- quadratic formula with overall time: BED = nd (1 + d/ [alpha/beta]) - log(e)2 (T - Tk) / alphaTp, where BED is BED = total dose x relative effectiveness (RE = nd (1 + d/ [alpha/beta]). Each of the five biologic parameters in turn was altered by +/-10%, and the altered EQD2s tabulated; the difference was finally divided by 20. EQD2 or NTD is obtained by dividing BED by the RE for 2-Gy fractions, using the appropriate alpha/beta ratio.


RESULTS
Variations in tumor and acute mucosal EQD ranged from 0.1% to 0.45% per 1% change in each parameter for conventional schedules, the largest variation being caused by overall time. Variations in "late" EQD were 0.4% to 0.6% per 1% change in the only biologic parameter, the alpha/beta ratio. For stereotactic body radiotherapy schedules, variations were larger, up to 0.6 to 0.9 for tumor and 1.6% to 1.9% for late, per 1% change in parameter.


CONCLUSIONS
Robustness occurs similar to that of equivalent uniform dose (EUD), for the same reasons. Total dose, dose per fraction, and dose-rate cause their major effects, as well known.
Fowler
Jack F
JF
Department of Human Oncology, School of Medicine, University of Wisconsin, Madison, WI, USA. jackfowlersbox@gmail.com
D000465:Algorithms; D049109:Cell Proliferation / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D009061:Mouth Mucosa / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology; D011836:Radiation Tolerance; D011853:Radiobiology; D016634:Radiosurgery / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012680:Sensitivity and Specificity; D013997:Time Factors