21 years of Biologically Effective Dose

Abstract

ABSTRACT. In 1989 the British Journal of Radiology published a review proposing the term biologically effective dose (BED), based on linear quadratic cell survival in radiobiology. It aimed to indicate quantitatively the biological effect of any radiotherapy treatment, taking account of changes in dose-per-fraction or dose rate, total dose and (the new factor) overall time. How has it done so far? Acceptable clinical results have been generally reported using BED, and it is in increasing use, although sometimes mistaken for ''biologically equivalent dose'', from which it differs by large factors, as explained here. The continuously bending nature of the linear quadratic curve has been questioned but BED has worked well for comparing treatments in many modalities, including some with large fractions. Two important improvements occurred in the BED formula. First, in 1999, high linear energy transfer (LET) radiation was included; second, in 2003, when time parameters for acute mucosal tolerance were proposed, optimum overall times could then be ''triangulated'' to optimise tumour BED and cell kill. This occurs only when both early and late BEDs meet their full constraints simultaneously. New methods of dose delivery (intensity modulated radiation therapy, stereotactic body radiation therapy, protons, tomotherapy, rapid arc and cyberknife) use a few large fractions and obviously oppose well-known fractionation schedules. Careful biological modelling is required to balance the differing trends of fraction size and local dose gradient, as explained in the discussion ''How Fractionation Really Works''. BED is now used for dose escalation studies, radiochemotherapy, brachytherapy, high-LET particle beams, radionuclide-targeted therapy, and for quantifying any treatments using ionising radiation.

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with131I-mIBG

“…The ratio of BEDTum to the BED of organs at risk has been suggested as a clinically useful metric to choose between different fractionation schemes in EBRT (Fowler, 2010). In MRT we believe that this BED-ratio may be interesting, since BEDTum and the BED of organs at risk cannot be treated separately, but both depend on the amount of administered activity.…”

Erratum

“…Biologically equivalent dose was calculated using the simple biologically equivalent dose equation without correction for repopulation. 16 Disease recurrence was coded as local recurrence (ie, occurring in the treated primary site), locoregional recurrence (ie, occurring in the treated primary site or treated lymph nodes), or distant metastases (ie, squamous carcinomas occurring outside the treated head and neck). Because records of distant metastases and second primary squamous carcinomas could not be reliably separated, these pathologies were grouped together as metastatic events in the current analysis.…”

Personalized Medicine in Prostate Cancer: Future Perspectives for Tailored Treatments

“…In fact, more advanced technologies have been adopted in clinical use in the last decade, such as image guided radiation therapy, different advanced dose modulation and delivery techniques, particle therapy, with a increasing attention to address resources in a reliable and cost-effective technologies [4]. Furthermore, radiotherapy is actually more a biological intervention rather than a physical, because of its effects on cellular and molecular level [7][8]; the heterogeneity of dose distribution in the irradiated and normal tissue should be considered [1]. In the past, in order to analyse the treatment effects in radiation oncology, several models were elaborated, to show the correlation between radiotherapy dose and outcomes, through different dose-reduction methods; the probit-based one (or the Lyman--Kutcher-Burman model) [9] and the logit-based one [10] are the most used dose-response models.…”