A theoretical investigation into the role of tumour radiosensitivity, clonogen repopulation, tumour shrinkage and radionuclide RBE in permanent brachytherapy implants of 125I and 103Pd.

There is growing clinical interest in the use of 125I (half-life 59.4 days) and 103Pd (half-life 16.97 days) for permanent brachytherapy implants. These radionuclides pose interesting radiobiological challenges because, even with slowly growing tumours, significant tumour cell repopulation may occur during the long period taken to deliver the full radiation dose. This results in a considerable amount of the prescribed dose being wasted. There may also be changes in the tumour volume during treatment (due to oedema and/or shrinkage), thus altering the relative geometry of the implanted seeds and causing additional dose rate variations. This assessment examines the interaction between the above effects and additionally includes allowance for the influence of the relative biological effectiveness (RBE) of the radiations emitted by the two radionuclides. The results are presented in terms of the biologically effective doses (BEDs) and likely tumour control probabilities (TCPs) associated with the various parameter combinations. The overall BED enhancement due to the RBE effect is shown always to be greater than the RBE itself and is greatest in tumours which are radio-resistive and/or fast growing. The biological dose uncertainties are found to be less with 103Pd and the TCPs associated with this radionuclide are expected to be significantly higher in the treatment of some 'difficult' tumours. Using typically prescribed doses 125i appears to be better for treating radiosensitive tumours with long doubling times and which shrink fairly rapidly. However, unless 125I doses are reduced, this advantage may well be offset by the greatly enhanced biological doses delivered to adjacent normal structures.

Calculation of integrated biological response in brachytherapy.

PURPOSE: To present analytical methods for calculating or estimating the integrated biological response in brachytherapy applications, and which allow for the presence of dose gradients. METHODS AND MATERIALS: The approach uses linear-quadratic (LQ) formulations to identify an equivalent biologically effective dose (BEDeq) which, if applied to a specified tissue volume, would produce the same biological effect as that achieved by a given brachytherapy application. For simple geometrical cases, BED multiplying factors have been derived which allow the equivalent BED for tumors to be estimated from a single BED value calculated at a dose reference point. For more complex brachytherapy applications a voxel-by-voxel determination of the equivalent BED will be more accurate. Equations are derived which when incorporated into brachytherapy software would facilitate such a process. RESULTS: At both high and low dose rates, the BEDs calculated at the dose reference point are shown to be lower than the true values by an amount which depends primarily on the magnitude of the prescribed dose; the BED multiplying factors are higher for smaller prescribed doses. The multiplying factors are less dependent on the assumed radiobiological parameters. In most clinical applications involving multiple sources, particularly those in multiplanar arrays, the multiplying factors are likely to be smaller than those derived here for single sources. The overall suggestion is that the radiobiological consequences of dose gradients in well-designed brachytherapy treatments, although important, may be less significant than is sometimes supposed. The modeling exercise also demonstrates that the integrated biological effect associated with fractionated high-dose-rate (FHDR) brachytherapy will usually be different from that for an "equivalent" continuous low-dose-rate (CLDR) regime. For practical FHDR regimes involving relatively small numbers of fractions, the integrated biological effect to tissues close to the treatment sources will be higher with HDR than for LDR. Conversely, the integrated biological effect on structures more distant from the sources will be less with HDR. This provides quantitative confirmation of an idea proposed elsewhere, and suggests the existence of a potentially useful biological advantage for HDR brachytherapy delivered in relatively small fraction numbers and which is not apparent when considering radiobiological effect only at discrete reference points. CONCLUSION: The estimation and direct calculation of integrated biological response in brachytherapy are both relatively straightforward. Although the tabular data presented here result from considering only simple geometrical cases, and may thus overestimate the consequences of dose gradients in multiplanar clinical applications, the methods described may open the way to the development of more realistic radiobiological software, and to more systematic approaches for correlating physical dose and biological effect in brachytherapy.

Iodine seeds in the treatment of slowly proliferating tumours in the head and neck region.

Locally recurrent/persistent disease is a major cause of morbidity and mortality in patients suffering from tumours arising in the head and neck region. Iodine-125, with its long half-life of 60 days, is particularly suited for the treatment of slowly proliferating tumours (e.g. adenoidcystic carcinomas) of this site. We report our experience with 18 patients using iodine-125 seeds, placed at the time of surgery in patients with such tumours. Eleven of the patients were treated for recurrent disease following previous radical treatment. Disease free survival was 89% at 2 years and 53% at 5 years after treatment. These results are encouraging in a group of patients in whom achieving and maintaining local control can be extremely difficult.

Effect of tumour shrinkage on the biological effectiveness of permanent brachytherapy implants.

A tumour shrinkage factor is incorporated into previously derived linear-quadratic (LQ) formulae which allowed radiobiological assessment of the efficacy of permanently implanted radionuclides. The new formulations relate the biologically effective dose (BED) to radionuclide half-life, recovery half-life, tumour radiosensitivity, potential doubling time and linear shrinkage rate. Specific attention has been given to the following radionuclides: gold-198 (half-life, 2.7 days), palladium-103 (half-life, 17 days), ytterbium-169 (half-life, 32 days) and iodine-125 (half-life, 60 days). For each nuclide the log cell kill resulting from typically prescribed doses was calculated for a range of tumour clonogen doubling times at various radiosensitivities and linear shrinkage rates. It is shown that even relatively modest shrinkage rates are capable of enhancing the clinical potential of the longer-lived nuclides. However, even though the effect of tumour shrinkage is minimal in the case of gold-198, for fast growing and/or insensitive tumours there are fewer radiobiological uncertainties associated with the use of this nuclide. The revised equations may also have applications in certain types of biologically targeted radiotherapy.

The potential of ytterbium 169 in brachytherapy: a brief physical and radiobiological assessment.

Ytterbium 169 (half-life 32 days; mean gamma emission 93 keV, after excluding photons of energy less than 10 keV) is a radionuclide with interesting potential for brachytherapy applications. Although not yet commercially available, its possible application as a clinical radionuclide is currently being considered by Amersham International. This article presents an assessment of some properties of the nuclide that may be clinically relevant. Use is made of some new ideas that allow quantification of the likely dose homogeneity that can be obtained in a brachytherapy distribution, and in this context ytterbium 169 is shown to be superior to some currently available brachytherapy nuclides. The assessment also uses recent extensions to the linear-quadratic model to consider the likely radiobiological implications associated with the use of the nuclide. From this it is suggested that the main potential for ytterbium 169 would be as a source that may be re-used for a number of short-term applications, rather than as a permanently implantable nuclide.

A Fortran program for fast and compact processing of clinical radiotherapy data.

A set of Fortran IV programs have been developed to enable a patient registry to operate on a minicomputer of a type frequently used for treatment planning within radiotherapy departments. The system is both comprehensive and flexible, allowing the efficient storage of clinical data in the form of coded units. The coding format used enables inexperienced operators to enter, or extract data from the system with the minimum of keyboard operations.

Feasibility of absolute activity measurements using the Cleon emission tomography system.

Large volume and small discrete sources of Tc-99m were used to study the spatial resolution, sensitivity, linearity and reproducibility of the radionuclide brain images. The spatial resolution is constant both within and perpendicular to the section. For uniform distributions of activity the response is uniform over the field of view, and the mean pixel count rate is a linear function of the radioactive concentration and is independent of the diameter of the source. However, for discrete sources, the sensitivity was found to vary with the position of the source, and the potential of the system for quantitative assessment of the uptake of radioactivity in organs and tumors was limited initially. Later studies, with modified software, show that this undesirable effect has been reduced.