Dose-rate Effects: Some Theoretical and Practical Considerations

Fowler, Joh N F.; Stern, Babette E.

doi:10.1259/0007-1285-33-390-389

Cited by 46 publications

(13 citation statements)

References 2 publications

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“…Simply, when higher dose rates are delivered to an organ, greater cellular lethality will occur (43,48,51). As shown in the previous section and in Figure 1A, this dose-rate effect is dependent on the intrinsic a/b-ratio (related to tissue radiosensitivity) and the repair half-time for the irradiated tissue.…”

Section: Example 1: Effect Of Dose Ratementioning

confidence: 80%

“…To account for the biologic effect of dose rate, the LQ model has been used to derive a biologically effective dose (BED). BED is related to the logarithmic cell kill, and because the radiobiologic model parameters differ between tumors and normal tissues, there are different BED values for each irradiated tissue (35,42,43). The original BED is a cell survival model in which all cells receive the same absorbed dose and are subject to the same temporal pattern of absorbed dose.…”

Section: Theoretic Basis and Model Equationsmentioning

confidence: 99%

“…The factor g(T), introduced in Equation 2, which accounts for incomplete repair as a function of time, can also be used to correct for the low dose rates associated with targeted radiotherapy (43,46). It has been suggested that the kidney be considered a collection of functional subunits (or FSUs) such that it may be useful to view the toxicity in terms of FSU survival rather than survival at a cellular or a whole-organ level.…”

Section: Application Of Lq and Bed Models To Kidneymentioning

confidence: 99%

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MIRD Pamphlet No. 20: The Effect of Model Assumptions on Kidney Dosimetry and Response—Implications for Radionuclide Therapy

Wessels¹,

Konijnenberg²,

Dale³

et al. 2008

J Nucl Med

163

114

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Renal toxicity associated with small-molecule radionuclide therapy has been shown to be dose-limiting for many clinical studies. Strategies for maximizing dose to the target tissues while sparing normal critical organs based on absorbed dose and biologic response parameters are commonly used in external-beam therapy. However, radiopharmaceuticals passing though the kidneys result in a differential dose rate to suborgan elements, presenting a significant challenge in assessing an accurate dose-response relationship that is predictive of toxicity in future patients. We have modeled the multiregional internal dosimetry of the kidneys combined with the biologic response parameters based on experience with brachytherapy and external-beam radiation therapy to provide an approach for predicting radiation toxicity to the kidneys. Methods: The multiregion kidney dosimetry model of MIRD pamphlet no. 19 has been used to calculate absorbed dose to regional structures based on preclinical and clinical data. Using the linear quadratic model for radiobiologic response, we computed regionally based surviving fractions for the kidney cortex and medulla in terms of their concentration ratios for several examples of radiopharmaceutical uptake and clearance. We used past experience to illustrate the relationship between absorbed dose and calculated biologically effective dose (BED) with radionuclide-induced nephrotoxicity. Results: Parametric analysis for the examples showed that high dose rates associated with regions of high activity concentration resulted in the greatest decrease in tissue survival. Higher dose rates from short-lived radionuclides or increased localization of radiopharmaceuticals in radiosensitive kidney subregions can potentially lead to greater whole-organ toxicity. This finding is consistent with reports of kidney toxicity associated with early peptide receptor radionuclide therapy and 166 Ho-phosphonate clinical investigations. Conclusion: Radionuclide therapy doseresponse data, when expressed in terms of biologically effective dose, have been found to be consistent with external-beam experience for predicting kidney toxicity. Model predictions using both the multiregion kidney and linear quadratic models may serve to guide the investigator in planning and optimizing future clinical trials of radionuclide therapy.

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Section: Example 1: Effect Of Dose Ratementioning

confidence: 80%

Section: Theoretic Basis and Model Equationsmentioning

confidence: 99%

Section: Application Of Lq and Bed Models To Kidneymentioning

confidence: 99%

See 1 more Smart Citation

MIRD Pamphlet No. 20: The Effect of Model Assumptions on Kidney Dosimetry and Response—Implications for Radionuclide Therapy

Wessels¹,

Konijnenberg²,

Dale³

et al. 2008

J Nucl Med

163

114

View full text Add to dashboard Cite

show abstract

“…The BJR has played a large part in these developments, starting with the first tentative mention of LQ in relation to radiotherapy [17,18]. Then followed many fractionation animal experiments [19] and early modelling [4][5][6][7], including the first published mention of the crucial mouse skin experiments [20].…”

Section: The Role Of the British Journal Of Radiologymentioning

confidence: 99%

21 years of Biologically Effective Dose

Fowler¹

2010

BJR

532

448

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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.

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“…1 and 2. Fowler and Stern (1958; examined the implications of dose-effect curves having a term proportional to dose squared in addition to one proportional to dose (Gray and Scholes, 1951). Since then, cell survival curves for a number of mammalian cells in vitro and in vivo have been found to have shapes which are similar to each other (Gray, 1959a).…”

Section: Total Dosementioning

confidence: 99%