Abstract
BackgroundThe kidneys are a principal dose-limiting organ in radiotherapy for upper abdominal cancers. The current understanding of kidney radiation dose response is rudimentary. More precise dose-volume response models that allow direct correlation of delivered radiation dose with spatio-temporal changes in kidney function may improve radiotherapy treatment planning for upper-abdominal tumours.Our current understanding of kidney dose response and tolerance is limited and this is hindering efforts to introduce advanced radiotherapy techniques for upper-abdominal cancers, such as intensity-modulated radiotherapy (IMRT). The aim of this study is to utilise radiotherapy and combined anatomical/functional imaging data to allow direct correlation of radiation dose with spatio-temporal changes in kidney function. The data can then be used to develop a more precise dose-volume response model which has the potential to optimise and individualise upper abdominal radiotherapy plans.Methods/designThe Radiotherapy of Abdomen with Precise Renal Assessment with SPECT/CT Imaging (RAPRASI) is an observational clinical research study with participating sites at Sir Charles Gairdner Hospital (SCGH) in Perth, Australia and the Peter MacCallum Cancer Centre (PMCC) in Melbourne, Australia. Eligible patients are those with upper gastrointestinal cancer, without metastatic disease, undergoing conformal radiotherapy that will involve incidental radiation to one or both kidneys. For each patient, total kidney function is being assessed before commencement of radiotherapy treatment and then at 4, 12, 26, 52 and 78 weeks after the first radiotherapy fraction, using two procedures: a Glomerular Filtration Rate (GFR) measurement using the 51Cr-ethylenediamine tetra-acetic acid (EDTA) clearance; and a regional kidney perfusion measurement assessing renal uptake of 99mTc-dimercaptosuccinic acid (DMSA), imaged with a Single Photon Emission Computed Tomography / Computed Tomography (SPECT/CT) system. The CT component of the SPECT/CT provides the anatomical reference of the kidney’s position. The data is intended to reveal changes in regional kidney function over the study period after the radiotherapy. These SPECT/CT scans, co-registered with the radiotherapy treatment plan, will provide spatial correlation between the radiation dose and regional renal function as assessed by SPECT/CT. From this correlation, renal response patterns will likely be identified with the purpose of developing a predictive model.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12609000322235
Highlights
The kidneys are a principal dose-limiting organ in radiotherapy for upper abdominal cancers
Study hypotheses An assessment of changes in total kidney function, regional kidney functional change and their correlation with radiotherapy dose delivery is within the means of currently available imaging, therapy and computational technology
– Temporal variations in Single Photon Emission Computed Tomography (SPECT) images of the kidneys correlate with patterns of radiation dose delivery in the kidneys
Summary
The kidneys are a principal dose-limiting organ in radiotherapy for upper abdominal cancers. More precise dose-volume response models that allow direct correlation of delivered radiation dose with spatio-temporal changes in kidney function may improve radiotherapy treatment planning for upper-abdominal tumours. Radiotherapy has a significant role to play in the management of cancers of the upper abdomen, but high dose radiotherapy has been considerably limited by potential adverse normal tissue responses, in particular that of the kidneys Because of their proximity to organs such as the pancreas, stomach and oesophagus, incidental radiation dose to the kidneys is frequently unavoidable when planning radiotherapy treatment. Our current understanding of kidney dose response and tolerance to radiation is rudimentary This limits the delivery of a higher dose to the tumour and the introduction and optimisation of new techniques to treat these upper gastrointestinal cancers, such as intensity modulated radiation therapy (IMRT). Studies in pigs [7,8] have shown that the response is dependent on whether one or both kidneys are irradiated and that the functional response depends on the compensatory response of the non-irradiated kidney
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