The frequent need to obtain an estimate of renal function in cancer patients, not least for targeting carboplatin dose, has led to a number of approaches to estimate glomerular filtration rate (GFR). This study aimed to develop a simple and reliable method to estimate GFR using readily-available patient characteristics. Data from 62 patients with estimates of 51 Cr-EDTA clearance were analysed to determine the most appropriate formula relating this method of measuring GFR to patient characteristics. The population pharmacokinetics of 51 Cr-EDTA were analysed using NONMEM to evaluate the influence of each covariate. The formulae derived were then validated using a further 38 patients and compared with those obtained using existing formulae 51 Cr-EDTA clearance (GFR) was positively related to Dubois surface area, negatively related to age, and inversely related to serum creatinine (SCr). Females had lower 51 Cr-EDTA clearance than males. The enzymatic method of SCr assay gave more reliable results than the Jaffe colorimetric method. A measure of creatine kinase significantly improved the estimation of GFR. The new formula produced estimates of GFR which were less biased (Mean Prediction Error = –3%) and more precise (Mean Absolute Prediction Error = 12%) than Cockcroft and Gault (–8% and 16%) or Jelliffe (–15% and 19%) estimates. The formulae developed here can be used to provide reliable estimates of GFR, particularly in regard to targeted dosing of carboplatin. © 2001 Cancer Research Campaign http://www.bjcancer.com
Objective: To improve medulloblastoma proton therapy. Although considered ideal for proton therapy, there are potential disadvantages. Expected benefits include reduced radiation-induced cancer and circulatory complications, while avoiding small brain volumes of dose in-homogeneity when compared with conventional X-rays. Several aspects of proton therapy might contribute to reduced tumour control due to (a) the use of more homogenous dose levels which can result in under-dosage, (b) differences in relative biological effectiveness (RBE) between that prescription RBE of 1.1 and the RBE of brain and spinal cord (likely to exceed 1.1) and in medulloblastoma cells (where RBE is likely to be below 1.1). Such changes, although speculative for RBE, might result in potential underdosage of tumour cells and a higher bio-effect in brain tissue. Methods: Dose distributions for X-ray and proton treatment are compared, with allocation of likely RBE values for fast growing medullolastoma cells and stable central nervous system tissue. Results: These physical and radiobiological factors are shown to combine to give a higher risk of tumour recurrence with further risks on tumour control when dose reduction schedules used for X-ray therapy are replicated for proton therapy for ''low-risk'' patients. Conclusion: The dose distributions and prescribed doses of proton therapy, taking into account RBE, in children and adults with medulloblastoma, need to be reconsidered. The medulloblastoma tumour, which most commonly arises in childhood, is normally treated by subtotal surgical excision, with or without cytotoxic chemotherapy, but always with post-operative radiotherapy to the whole brain and spinal column, which results in impressive cure rates of around 70-80%. The highest radiation dose is given to the posterior fossa of the brain where the tumour originates, but a lower dose is given to the remaining brain and spinal cord tissues using X-rays or protons [1][2][3][4] because of the risk of later tumour growth in these regions as a consequence of tumour cells deposited on neural surfaces due to spread of the tumour via the cerebrospinal fluid (CSF). Unlike X-rays, a posterior spinal proton beam using a selected energy range does not incur an ''exit beam'' dose to organs anterior to the spinal tissues, and so reduces the risk of future carcinogenesis [5], circulatory complications [6] and potentially some cases of female infertility. Such complications can occur after a relatively low dose of Xray exposure, such as in the 5-30 Gy range.Proton therapy dose distributions depend on the Bragg peak effect and can be delivered using broad ''passively scattered'' beams or by multiple individual pencil beams. Spread of the tumour from the primary site occurs through the CSF to other areas of the brain or spine. The aim of proton therapy is to deliver a homogeneous dose across the brain and spinal cord. The CSF-containing regions must be included, especially the cisterns and ventricles of the brain, and all subarachnoid spaces, including th...
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