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Bleddyn Jones

Publications and source records attributed to Bleddyn Jones.

6 recordsLinked to original sources
PubMed2006

Linear quadratic modeling of increased late normal-tissue effects in special clinical situations.

PURPOSE: To extend linear quadratic theory to allow changes in normal-tissue radiation tolerance after exposure to cytotoxic chemotherapy, after surgery, and in elderly patients. METHODS: Examples of these situations are analyzed by use of the biologic effective dose (BED) concept. Changes in tolerance can be allowed for by: estimation of either the contribution of the additional factor as an equivalent BED or the equivalent dose in 2-Gy fractions or by the degree of radiosensitization by a mean dose-modifying factor (x). RESULTS: The estimated x value is 1.063 (95% confidence limits for the mean, 1.056 to 1.070) for subcutaneous fibrosis after cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and radiotherapy in breast cancer. The point estimate of x is 1.18 for the additional risk of gastrointestinal late-radiation effects after abdominal surgery in lymphoma patients (or 10.62 Gy at 2 Gy per fraction). For shoulder fibrosis in patients older than 60 years after breast and nodal irradiation, x is estimated to be 1.033 (95% confidence limits for the mean, 1.028 to 1.0385). The equivalent BED values were CMF chemotherapy (6.48 Gy3), surgery (17.73 Gy3), and age (3.61 Gy3). CONCLUSIONS: The LQ model can, in principle, be extended to quantify reduced normal-tissue tolerance in special clinical situations.

Aged↗
PubMed2003

Application of biological effective dose (BED) to estimate the duration of symptomatic relief and repopulation dose equivalent in palliative radiotherapy and chemotherapy.

PURPOSE: To investigate the potential for mathematic modeling in the assessment of symptom relief in palliative radiotherapy and cytotoxic chemotherapy. METHODS: The linear quadratic model of radiation effect with the overall treatment time and the daily dose equivalent of repopulation is modified to include the regrowth time after completion of therapy. RESULTS: The predicted times to restore the original tumor volumes after treatment are dependent on the biological effective dose (BED) delivered and the repopulation parameter (K); it is also possible to estimate K values from analysis of palliative treatment response durations. Hypofractionated radiotherapy given at a low total dose may produce long symptom relief in slow-growing tumors because of their low alpha/beta ratios (which confer high fraction sensitivity) and their slow regrowth rates. Cancers that have high alpha/beta ratios (which confer low fraction sensitivity), and that are expected to repopulate rapidly during therapy, are predicted to have short durations of symptom control. The BED concept can be used to estimate the equivalent dose of radiotherapy that will achieve the same duration of symptom relief as palliative chemotherapy. CONCLUSION: Relatively simple radiobiologic modeling can be used to guide decision-making regarding the choice of the most appropriate palliative schedules and has important implications in the design of radiotherapy or chemotherapy clinical trials. The methods described provide a rationalization for treatment selection in a wide variety of tumors.

Carcinoma↗
PubMed2003

The determination of radiobiologically optimized half-lives for radionuclides used in permanent brachytherapy implants.

PURPOSE: To use tumor growth kinetics and other biologic parameters in an extended version of the linear-quadratic (LQ) formulation to determine radiobiologically optimized half-lives of radionuclides which might be used in permanent brachytherapy implants. METHODS AND MATERIALS: A version of the LQ model suitable for the analysis of permanent brachytherapy implants has been modified to investigate the radionuclide half-lives that will maximize the biologically effective dose (BED) delivered to tumors with repopulation rates (K values) in the range 0.01-1.1 Gyday(-1). The method assumes that part of the physical dose delivered to the tumor may be radiobiologically wasted because of the repopulation phenomenon, whereas adjacent normal tissues will exhibit little or no wastage. To perform the analysis, it is necessary to stipulate alpha/beta ratios and sublethal damage recovery rates together with the normal tissue tolerance BED. The analysis also takes into account a range of likely relative biological effectiveness (RBE) values. RESULTS: Rapidly growing tumors require the shortest radionuclide half-lives, but even slow-growing tumors such as prostate adenocarcinomas can be satisfactorily treated with radionuclides possessing half-lives substantially less than that associated with I(125). The likelihood that prostate tumors possess an alpha/beta value which is comparable with, or lower than, that associated with late-responding normal tissues would also mitigate against the use of long-lived radionuclides. Although a number of parameter assumptions are involved, the results suggest that, for a wide range of tumor types, shorter-lived radionuclides are more versatile for achieving reasonable clinical results. The theoretically derived optimum half-lives typically range from around 0-5 days for fast-repopulating tumors (K 1.1 Gyday(-1)) to approximately 14-50 days for slow-growing tumors (K approximately 0.1 Gyday(-1) or less). For prostate implantation, 103Pd is overall a better choice than 125I. CONCLUSION: With so many variables and parameter uncertainties, it is not appropriate to attempt to define optimum radionuclide half-lives too closely. However, this study suggests that half-lives in the approximate range 4-17 days are likely to be significantly better for a wide range of tumor types for which the radiobiologic characteristics may not be precisely known in advance.

Brachytherapy↗