Longitudinal study of MRI and Spectroscopy techniques in evaluation of the natural history of Low Grade Gliomas.(Dr. Jeremy Rees)
3 Year Funding of £87,500 by SDBTT ASTRO FUND
2001 - 2004
Conventional management of low-grade gliomas (LGGs) is conservative because there is no evidence that early treatment with either surgery or radiotherapy confers any survival advantage or prevents subsequent malignant transformation. Most people adopt a ‘wait and see’ policy and only intervene if the clinical or radiological features suggest progression. This may not be sensitive to the earliest changes of malignant transformation, the process by which these tumours progress from a low-grade into a high grade lesion.
Low-grade gliomas of the cerebral hemispheres are common in both children and adults and comprise more than 50% of primary brain tumours. In adults, they are associated with a median survival of 5-10 years with five and ten year survival rates of 66 and 43 respectively. Patients may, therefore, live for many years without symptoms apart from epilepsy. They infiltrate adjacent brain structures diffusely and have an inherent tendency to transform into malignant gliomas at an unpredictable time in their natural history. This process is associated with neurological symptoms including raised intracranial pressure, worsening epilepsy and progressive focal deficit.
This project aims to harness advanced imaging techniques to predict the earliest stages of malignant transformation of adult low-grade gliomas in order to institute appropriate treatment at an early stage, before neurological deterioration. The development of these techniques will also be applicable to the field of therapeutic monitoring of brain tumour responses in general.
To date, 56 patients have been recruited of whom 27 are still being actively scanned, 18 have transformed, 7 have left the project for various reasons and 4 were excluded after their first scan when it became apparent they were not appropriate. Post processing methodologies are being developed to analyse the large amount of data now collected.
Using inhouse software to measure tumour volumes in consecutive scans we have derived annual growth rates amongst twenty stable patients and compared them with growth rates derived from the final (6 months before) and the penultimate (12 to 6 months before) time intervals amongst seven transformers. We have found that there are striking differences in average growth rates between transformers and non-transformation. Of even more interest is that there is also some acceleration of growth six to twelve months before the transformation scan although it is not large enough to predict reliably malignant change in an individual patient. At present these are preliminary results and it is essential to gather further data with longer follow-up periods and more patients being able to define threshold growth rates above which transformation can be reliably predicted.
Conclusions:
Observed growth rates are higher in the time period immediately before diagnosis of transformation. There was also a more modest increase in tumour growth rates in the six months immediately prior to the final time period heralding transformation, indicating a trend towards possible identification of early malignant transformation six months before the event.
These data are exciting but are limited by the relatively short follow-up time in the natural history of these tumours and small numbers of patients. Further work over the next three years is necessary to define the volume changes in greater detail and to draw up recommendations for scanning patients with low-grade gliomas to optimize the chances of early detection of malignant transformation.
Other imaging modalities e.g. fluid registration techniques are being investigated and will form the basis of a second grant application.
In the long run, it is hoped that development and validation of these advanced techniques will lead to better understanding of the natural history of untreated LGGs and enable us to predict the earliest stages of malignant transformation. By establishing a ‘therapeutic window’ of opportunity for early intervention, clinical trials can be designed to determine the most appropriate therapy for early disease, with the ultimate hope of improving outcome.
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